Protecting the Arch Length of the Developing Dentition

Introduction

For the past several decades the suggested protection for any real or potential loss of mandibular and/or maxillary arch length has been the placement of a fixed lingual arch (LA) or a fixed/removable lingual arch (FRLA). Other appliances have also been in vogue…among them the Ricketts Utility Arch or “U” arch.

This blog attempts to enable the practitioner to make wise choices when arch length management is under consideration. The soldered lingual arch is likely the first appliance to be considered, followed by the fixed/removable lingual arch (FRLA). While the Ricketts Utility Arch has numerous functions, this appliance appears to be utilized primarily by the orthodontic practitioner. However, there has been a steady movement toward the use of a “U” arch by non-extraction practitioners as a 1st Phase appliance. The use of a “U” arch by Pediatric Dental practitioners for arch length control makes sense because loss of arch length is common and the regaining of space for erupting premolars and canines is of utmost importance. The lingual arch holds arch length quite well, however this appliance cannot easily regain lost arch length in the mixed dentition phase of oro-dental maturation. The FRLA has some benefits over the soldered lingual arch and its use in the hands of well-informed practitioners can result in arch length improvement. In general, the discrete bends required to increase arch length will require substantial skill in archwire bending and manipulation. Auxiliaries soldered to lingual archwires can also be helpful and in some cases the lost arch length can be recovered. There are alternatives to the lingual arch that can substantially improve upon mixed dentition arch length management.

The Ricketts Utility Arch

The primary molars retain a remarkable capacity to hold arch length. However, any mesial movement of the first permanent molar will encroach upon arch length and can substantially decrease the space required for normal eruption of the premolars. If bilateral mesial movement is observed, the complication is multiplied…often to a severe degree. The distal surface of the second primary molar is the eruption “guide” for the 1st permanent molar and serves many important functions in the mixed dentition until it exfoliates at approximately 12 years of age. In addition, any lingual movement of the mandibular incisors will also impinge upon the arch lengthMany modifications of the original “U” arch design have been utilized to protect or modify the arch length in the mixed dentition. The design of the “U” arch appliance is not complicated and its use in the mixed dentition for arch length management by Pediatric Dentists should not be overlooked.The properly designed passive or activated “U” arch has the following advantages.

Advantages of the Utility Arch

1. Uprighting and rotational control of the permanent molar.

2. Control of the lower incisor segment…including intrusion, labial or lingual movement, and rotational control.

3. Ease of adjustment. Easily accessed anterior bracket engagement and no “tie back” on the permanent molar.

4.  Sectional management of the anterior and/or posterior segments that bypass the erupting premolars and canines.

5. An easily formed arch wire that utilizes a buccal entry of attachment.

6. Each section of the “U” arch…right or left can be adjusted independently.

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 The Intact Primary Dentition

A Diagnostic Protocol prior to Treatment

A basic set of pretreatment records is essential. Many of these requirements can be requested by prescription to laboratories that specialize in pre-treatment records.

1. Full Mouth Periapical X-Rays with Bitewing films

2. Lateral Cephalometric X-rays & Panoramic X-Ray

3. Orthodontic trimmed models

4. Intra-oral and extra-oral photographs (lateral and full face)

5. A lateral Cephalometric Tracing – Ricketts tracing recommended

The Transitional Dentition

When the primary teeth loosen and the new permanent incisor erupts, the dentition is in transition. The transition to all permanent teeth will be complete at about the 12th year excluding the third molars. During the transitional phase of oral maturation the position of the first permanent molar must be protected. Any oral pathology that allows a mesial shift of the first permanent molar or lingual displacement of the mandibular incisor segment must be avoided.

Loss of Arch Length - Etiology

1. Interproximal caries with mesial shift of posterior quadrants.

2. Early loss of primary canines with midline shift.

3.  Extraction of primary teeth.

4. Ankylosis of primary molars.

5. Ectopic eruption of maxillary 1st permanent molars.

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Mesial Shift due to proximal caries

Early treatment for loss of arch length is essential if the patient is to avoid extended orthodontic treatment that often requires the extraction of premolars. Severe loss of arch length in the mixed dentition is often unable to be treated non-extraction and requires a serial extraction protocol. The potential loss of four premolars can solve a large arch length discrepancy, however an extraction protocol will require orthodontic management over the course of many months.

Point "A" depicted by red arrow

Point "A" depicted by red arrow

Point "Pog"&nbsp;depicted by red arrow

Point "Pog" depicted by red arrow

Ricketts Cephalometric Landmarks

Note that a line drawn from Point A to Pog should lie I millimeter behind the incisal tip of the lower incisor...on average. The potential answer to this conundrum is the use at the appropriate time of a Ricketts designed Utility Arch.The “U” arch may be activated to produce labial movement of the mandibular incisors if they are lingually inclined. In addition, the permanent molar can often be bucally rotated to gain some small amount of arch length increase.Using cephalometric standards for the mandibular incisor position to the APo line, a proposed labial advancement can be achieved. The Caucasian APo line standard is a +1 millimeter S.D. 2.  Other standards can also be applied at the discretion of the professional.

Hispanic Standard APo +4.7 mm - Standard Deviation

Japanese Standard APo +3 mm - Standard Deviation 2

African American Standard APo +5.2 mm - Standard Deviation 2

Rationale

If the lower incisors can be moved forward the resulting increase in arch length will be 2-millimeter gain for each 1 millimeter of forward movement of the mandibular incisor. The 2 to 1 “rule of thumb” is straightforward and comes from the dicta of the Steiner Cephalometric Analysis. Forward movement of the incisor segment is often able to convert an extraction case into a non-extraction diagnosis. But in addition, the uprighting or distal rotation of the mandibular molars can also create small amount of additional arch length.

Early treatment for loss of arch length is essential if the patient is to avoid extended orthodontic treatment that often requires the extraction of premolars. Severe loss of arch length in the mixed dentition is often unable to be treated non-extraction and requires a serial extraction protocol.

Leeway Space

The Early Mixed Dentition

The Early Mixed Dentition

It is well known that the mesio-distal dimension of the second primary molar is larger than the succedaneous bicuspid. There is a tendency to allow mesial movement of the first permanent molar because some practitioners believe that it is appropriate to allow the mesial movement of the molar to improve upon the Class I molar relationship.

It is true that on occasion mesial movement in the late mixed dentition occurs, but that fact should not condone mesial movement that impacts the arch length in the early mixed dentition phase of occlusal development. According to many observers the “leeway space” is utilized in its entirety by the distal movement of the erupting canine and premolars. The failure to keep the arch length intact in the early mixed dentition will often result in a crowded arch.

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Mesial Shift of First Molar over an Ankylosed Primary Molar

Mesial Shift of Posterior Quadrants

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Mesial shift of 1st Permanent Molar - Courtesy Dr. T. K. Barber

The loss of contact between the primary molars due to extensive carious involvement allows mesial movement of the permanent first molar and jeopardizes the arch length that is required for late mixed dentition eruption. The loss of contact is an important factor in the etiology of a crowded arch at maturation. The timing of intervention requires close observation of the developing dentition since substantial loss of arch length cannot be easily recovered. Many practitioners tend to closely guard the mandibular arch length since distalization of the mandibular molars often requires heroic action. Small amounts of arch length loss can often be recovered at the early mixed dentition stage, however larger amounts of loss often create the need for the extraction of a bicuspid in all four quadrants. In an overall sense, the critical nature of adequate arch length in every patient requires that the practitioner must use an appropriate appliance to protect the developing dentition when early loss of primary teeth has occurred.

Premature Loss of the Mandibular Primary Canine

Premature loss of a Primary Canine -&nbsp;Courtesy Dr. T. K. Barber

Premature loss of a Primary Canine - Courtesy Dr. T. K. Barber

The eruption of the mandibular incisors is often the first visible evidence that the dentition is in transition. When a primary mandibular canine exfoliates prematurely, the permanent lateral often erupts into a more distal relationship skewing the midline. This modification of the midline is a very early indication that the arch length has been compromised. Often the dental practitioner will recommend that the opposite primary canine be extracted to help maintain the midline relationship. This treatment plan many help to restore the midline alignment but arch length decrease may continue if the mandibular incisors assume a more lingual position. This lingual positioning may be due to abnormal contraction of the Mentalis upon deglutition, or oral habits may also be a contributing factor. Restoring the normal incisor relation to the A to Pog line should be considered as a possible treatment plan for the future. The “U” arch will likely be the first option when a repositioning plan is adopted. If the Mentalis muscle is at fault, bracket placement on the labial surface of the lower incisors will often be a deterrent to aberrant swallowing patterns. Keep in mind that labial repositioning the incisor segments forward one millimeter will result in a two millimeter arch length gain. The two for one relationship cannot be overlooked in managing a maturing mixed dentition.

Labial Movement of the Mandibular Incisors

If the lower incisors erupt into a position that is lingual to their normal position at a +1 to APo, then the arch length is decreased on the 2 to 1 dictum of Dr. Steiner. Lingual eruption is not unusual if the patient has a thumb/finger sucking habit or a modified pattern of deglutition. Tongue thrusting into an anterior open bite tends to allow the incisors to remain depressed and/or lingual to their intended cephalometric location. One the more important “watch-dog” duties of the Pediatric Dentist is to insure that the arch length is not compromised by habits or non-physiologic deglutition. Support for the incisor segment during the early mixed dentition phase is of the utmost importance for correct alignment of the succedaneous dentition.

Loss of Arch Length – Ankylosis

Minimal loss of arch length can easily occur when the posterior primary dentition fails to maintain the correct occlusal height. These molars appear to “submerge” when in actual fact they lack a true periodontal ligament that allows for physiologic eruption at the same rate as their adjoining posterior segments. The “tooth to bone” attachment firmly attaches the primary root to the alveolar bone and often creates arch length inadequacy. The practitioner must however be aware that the early signs of ankylosis should “raise a red flag” that something is amiss. Particularly at fault it the second primary molar that fails to keep pace with the eruption of the 1st permanent molar and the resulting occlusal discrepancy allows a mesial shift when the height of mesial contour over rides the distal contact of the second primary molar. The resulting mesial shift can create a very substantial loss of arch length, particularly when it occurs bilaterally or in several primary molars.

Primary molar ankylosis with complex pathology

The early diagnosis of primary molar ankylosis is an imperative considering that this oral anomaly creates many overriding oral pathologies. Close observation of the offending primary molars can result in an early diagnosis that demands the attention of the practitioner. 

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Loss of Occlusal Positioning suggesting ankylosis of the first and second primary molar and congenitally missing second bicuspid.

The loss of occlusal height is one of the first hints that this pathology is present. Bitewing x-rays will often be the first subjective sign that this progressive disease is impacting the development of the occlusion. Additional x-rays are indicated to ascertain the presence or absence of the succedaneous dentition. In addition, it may be necessary to prepare a long-term treatment plan that lists the options for early and/or late treatment. It may also be necessary to recommend that lateral cephalograms be taken to use as a reference tool as the oro-facial complex matures. At this time it may also be necessary to determine the facial growth pattern…is it Mesocephalic, Brachycephalic, or Dolichocephalic?

Cephalometrics

&nbsp; Ricketts Lateral Cephalogram

  Ricketts Lateral Cephalogram

The use of a cephalometric lateral x-ray at the mixed dentition phase of oral development is highly recommended. The early detection of the oro-facial growth facial pattern will give every practitioner the ability to prioritize treatment options and to predict the effect of growth. The Brachycephalic face (low angle) presents with options that may conflict with the treatment options presented by the Dolichocephalic facial (high angle) pattern of growth, while the Mesocephalic face suggests that a more normative treatment plan will be appropriate.

 A Cephalometric Mean for the Mandibular Incisor

&nbsp; Ricketts Lateral Cephalogram Essential Landmarks

  Ricketts Lateral Cephalogram Essential Landmarks

&nbsp;The A to Pog Line

 The A to Pog Line

The anterior-posterior position of the mandibular incisors relative to the “A to Pog” or “A” to Po” line is constant throughout life. The Caucasian standard is a plus 1-millimeter with a standard deviation of 2 millimeters. Other ethnic groups have standards that can be used to ascertain the mean and those standards can be used to plan treatment procedures. Many practitioners believe that this measurement is an essential factor in determining the treatment plan prior to instigating appliance therapy in the early mixed dentition. One of the more common results of long-term finger sucking habits is the lingual collapse of the incisor segment. Other landmarks are important in the development of a treatment plan and familiarity with every landmark is essential. The common use of the Bioprogressive Lateral Cephalometric x-ray analysis fits in well with Bioprogressive treatment philosophy.  The determination of growth pattern with successive overlays taken every two years will also allow the practitioner to assess treatment success. Essential to the ultimate treatment plan is the determination of the basic growth pattern…whether it is Mesocephalic, Brachycephalic, or Dolichocephalic. Each pattern of growth has its own treatment patterns that point to a successful outcome.

The “U” arch is a utilitarian method that improves on the general usage of the “age-old” lingual arch due to its ability to perform a variety of functions. A more general use of the “”U” arch by practitioners will improve the ability of most practitioners to reposition both posterior and anterior segments of the arch. This appliance will rotate and distalize the first permanent molar, de-rotate and reposition the incisor segments, and allow a segmental approach to early mixed dentition management. The segmental approach allows treatment to be directed to the anterior or posterior segments independently of each other. Varying anchorage positions can facilitate favorable response where required for maximum response.

In the case of primary molar ankylosis, the uprighting of the permanent molar or the maintenance of the arch length with a removable “U” arch could retain the correct arch length during the transitional period of primary to permanent eruption. In addition, it may be prudent to manage the position of the mandibular incisor segment. Subsequently a standard lingual arch may be required to retain the correct arch length.

The Anatomy of a “U” Arch

Anterior Segment – Distal of permanent lateral incisor to the distal of the antimere.

Buccal Bridge – Lateral incisors to the buccal tube of the permanent molar.

Molar Section – The extension into the buccal tube.

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The Mandibular “U” arch

Improving Posterior Anchorage

If additional posterior anchorage is desirable, the placement of a lingual arch can support the position of the molar anchorage and deliver anterior force only. If the lingual arch is fixed and removable, the anchorage needs can be added or removed as desired.

It is a basic tenet of Rickett’s philosophy that a segmental approach to treatment allows the erupting permanent bicuspids and canines to be excluded at the early stage of treatment. The subsequent addition of a segmental archwire in the more occlusal slot of the molar tube allows alignment of those teeth independently of the “U” arch. Later finishing of the entire arch can be accomplished with a single archwire either added to the “U” arch or used after the “U” arch is discarded.

Essential to this option is the attachment of brackets with a deeper slot dimension...030…thus enabling the addition of another “piggyback” archwire.

Cross Arch Anchorage plus “U” Arch

Cross Arch Anchorage plus “U” Arch

Utility Arch Construction

In the past the arch was constructed using a .016 x .016 Elgiloy preformed blank. Some practitioners prefer a stainless archwire that is .016 x .016. A slightly different size is often used in the maxillary arch…the .016 x .022. The permanent molars should be banded, but in some cases a bonded buccal tube may suffice. The mandibular incisors are bonded with twin brackets using a .018 x .025 slot dimension. Some practitioners prefer a greater depth to the slot and recommend a depth of .030. The arch wire engages the mandibular incisors and steps down at the lateral incisor/canine contact approximately 3 to 5 millimeters. It extends distally to the mesial of the molar tube where an occlusal bend of 3 to 4 millimeters for insertion into the molar tube. If the incisors are significantly misaligned, a four-incisor sectional leveling round archwire can be introduced until the entire .016 “U”archwire can be engaged. Some practitioners recommend a 4 to 5 mm step rather than 3 to 4 millimeters.

Ties

Engagement of the archwire into the anterior bracket slots is best accomplished by using elastomeric ties that are easily engaged using a mosquito hemostat. Wire ligatures may be required on occasion.

 Activation

The initial insertion of the “U” archwire is ordinarily placed as passive as possible. The incisor segment must be “leveled”, that is the bracket slots must align so that the .016 x .016 archwire can be engaged in the four incisor slots. The distal section that inserts into the buccal tube should also remain passive. The “bridge” section that spans the distance between the molar tube and the contact between primary canine and the permanent lateral incisor must also lie close to the soft tissue. If it is formed too wide it will impinge on the cheek and cause discomfort. The insertion into the buccal tube is not “tied back.” The insertion can be easily pulled out by the patient therefore some warning must be given to the patient. For the first visit it is acceptable to place a slight bend distal to the buccal tube to disallow removal by the patient until after the second visit.              

Synopsis

Many practitioners have some difficulty distinguishing tooth movement for specialty practitioners in Pediatric Dentistry versus some Orthodontic practitioners who typically use a “full hookup” in their management of malocclusion. This observer believes that the Pediatric specialist must support an adequate arch length during the mixed dentition period. That fact suggests that some patients who have misalignment due to pathology, mesial movement of permanent molars, or lingual collapse of the permanent incisors must be managed appropriately during the early mixed dentition. When habit patterns are also involved in the misalignment, the management will often fall into the specialty practice of the Pediatric Dentist. The “U” arch is an improvement over lingual arches that can be more difficult to manage particularly when maximum activation is required to control the arch length. If throughout the transition to permanent dentition the arch length is adequate, the permanent teeth will often erupt into a very satisfactory pre-orthodontic alignment.

The emphasis in this commentary is upon the treatment of the mandibular arch since the ultimate orthodontic diagnosis will often hinge upon the lower arch that is more difficult to manage than the components of the maxillary arch. Integral to this concept is the position in space of the mandibular incisors, since the stability and the requirements of arch length are built upon mandibular incisor position with esthetic normalcy. The Steiner 2 for 1 ratio in regard to the incisor position must always be in the mind of a practitioner who observes mandibular collapse associated with habits or poor deglutition physiology.

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The “U” Arch – Rickett’s design

The Utility Archwire is an appliance that can hold and to a degree upright the permanent molar and reposition the incisor segment during early mixed dentition should be in the armamentarium of every Pediatric Dentist. It is within our frame of reference to manage and correct early oral pathology that interferes with the normal transitional phase of oro-dental maturation…an objective well worth pursuing for Pediatric Dental patients. If later or second phase treatment is deemed advisable, the early “setup” of the mixed dentition can improve the final outcome of two-phase treatment. The maturation of the Utility Arch into a full Ricketts hookup is a second phase of management that may be required to complete many orthodontic cases. The specialty of Pediatric Dentistry may conclude that early intervention of arch length deficiencies is an important facet of our treatment regimen.

Suppliers

Rocky Mountain Orthodontics www.rmortho.com

Ortho Organizers www.orthoorganizers.com

Ormco www.ormco.com

American Orthodontics www.americanortho.com

Using “You Tube” to Review Construction and use of the “U” arch see:

https://www.youtube.com/watch?v=iW9GomNO0V0

You can search the web for the Ricketts Utility Arch for other related videos. The University of Michigan has several You Tube videos of the appliance and an interview with Dr. Ricketts.

                 

 

 

Epigenesis and Primary Molar Ankylosis

A Review of the “Functional Genome” – Chapter 2

Genomic and Precision Medicine. DOI: http://dx.doi.org/10.1016/B978-0-12-800681-8.00002-5

A review of Chapter 2 entitled “The Functional Genome: Epigenetics and Epigenomics clearly states that there is evidence that the epigenome can be transmitted from parent to offspring, creating the potential for heritable transmission without modifying the genome sequence.

DNA Methylation

    Commonly Modified Nucleotides

Chemically modified nucleotides are commonly expressed in the continuum of life and are thought to be limited to an addition of a methyl group to 5’ carbon in cytosine (5-methhylcytosine or 5mc) and then an addition of the hydroxy group to the methyl group to form 5-hydroxymethylcytosine (5hmC).  This modification modifies the nucleotide and changes the physical capacity of cellular activity.

Cytosine

Cytosine is a part of DNA, as part of RNA, or as a part of a nucleotide. In DNA and RNA, cytosine is paired with guanine. It is inherently unstable, and can change into uracil creating a spontaneous deamination. This action can lead to a point mutation if not modified by DNA repair enzymes. (from Wikipedia).

 

Cytosine

Cytosine

Methylation and Cytosines

The methylation of cytosine occurs when DNA methyltransferase (DNMT) family of enzymes come into play. The DNMT’s transfer a methyl group to the 5’ carbon of cytosine residues in the genome. This methylation is thought to be of prime importance to the establishment of a modified genome.

5-Methylcytosine (5mc)

Human cytosine methylation occurs very commonly when cytosine is followed by guanine in the genome. This junction is referred to as a CpG dinucleotide. To insure a better understanding of this biochemical expression, a review of that portion of the genome known as the heterochromatin must be sought.

Miller et al in Nature first identified 5mc in the literature in 1974. The genes in the heterochromatin are not generally expressed and 5mc was considered at that time to be an epigenetic mark that silences gene expression. That fact suddenly makes us aware that silencing of genetic material is a fact and that silencing of genetic information may play an integral role in the inability of pluripotent cells to differentiate into the precursor cells that will eventually produce the periodontal ligament (PDL) cells of the primary molar.

Silencing of Genetic Information

Silencing of a specific gene must be considered when the inquisitive observer seeks answers to specific oral disease that does not appear to have a chromosomal sequence etiology. Our present understanding of oral disease has often omitted the possibility that the epigenome may have a direct influence upon the creation of the basic anatomy of the primary molar.

We suggest that the loss of PDL precursor cells of the dental papilla impacts and silences the functional attributes of those cellular elements thus blocking the histologic formation of the PDL in the primary molar.  The inability of the cellular elements to morph into those cells that create the PDL completely blocks the formation of the alveolar attachment leading to primary molar ankylosis (PMA).

This specific oral pediatric dental anomaly occurs very often in the primary dentition, almost exclusively in the first and second primary molars. The pathology is often expressed more fully in the second primary molar and requires close observation as the ankylosis becomes more evident in the late primary dentition.

Radiographic Evidence

A close examination of a periapical x-ray of an offending primary molar will disclose the lack of a periodontal ligament. The cemental structure of the root structure will be continuous with the alveolar bone. This lack of PDL creates an ankylosis that renders the primary molar unable to properly assume a normal occlusal relationship.  As a consequence the first or second bicuspid is often displaced and unable to erupt into a normal occlusal relationship. Minimally affected primary molars may partially resorb and ultimately allow the eruption of the bicuspid into a delayed occlusal position.

Close observation of the periodontal status of all primary molars should be a positive requirement of recall appointments. Early identification and monitoring are essential elements in the treatment of PMA.

 

 

 

Transgenerational Inheritance and Primary Molar Ankylosis

A Review

Transgenerational Inheritance: Models and mechanisms of non-DNA sequence-based inheritance. E.A. Miska, A.C. Ferguson-Smith, Science 354, 59-63 (2016)

This review suggests the possibility of a non-DNA based sequence-based inheritance model that could be applied to Primary Molar Ankylosis (PMA). Older concepts that placed this oral pathology into a less defined etiology suggests that a conceptualization of an epigenetic etiology could materially influence the creation of a treatment plan that more correctly identifies the role played by a putative epigenetic etiology, thus maximizing the management of this oral disease.

The dental practitioner must carefully consider the ramifications of a treatment regimen that redefines the etiology of PMA into a newer genetic/epigentic category that will improve our construction of a treatment plan. Our treatment protocols would then allow a more complete visualization of the pathology and generate a treatment plan that fits the projected model of progression based upon new information contained within the research community. The adoption of the revised treatment protocol based on a newer thesis of etiology will likely allow current Pediatric Dental practitioners to more accurately define etiology and to define future outcomes more accurately.

A Dental Model for non-DNA sequence-based Inheritance

The contributor to this blog has often sought to blend the pure DNA model of inheritance with emerging tenets that extend the understanding of pure DNA inheritance with blending of an additional component…epigenetics. Extant inheritance models have some difficulty explaining how a pediatric dental patient can exhibit PMA that is too often simply explained as a post traumatic incident. Pediatric Dentistry has often not been able to succinctly describe the etiology of this anomaly that occurs quite often in the primary dentition. While the dental literature often suggests that there is hereditable component to this pathology, the exact nature of the etiology has yet to be described. The dental literature is often lacking an up-to-date survey of the literature is related to PMA. However, few research articles are able to expand on a growing awareness of the complicated etiology that surrounds the lack of the periodontal ligament in the primary dentition. A basic understanding of the role-played by genetics/ epigenetics is often missing which results in the distribution of misinformation to the profession and the general public. Our profession must address this issue by continuing to support research and provide aid to families that are afflicted with this oral pathology that severely modifies the eruption pattern of the succedaneous dentition An emerging model of epigenetic regulation has appeared in the literature that could clarify this pathology and provide a newer overview of treatment possibilities and the creation of awareness among Pediatric Dental practitioners. This pathology cannot be trivialized and practitioners and patients alike must be aware of the early stages of the disease that often initially presents as a minor occlusal problem. The initial diagnosis of PMA can be the simple observation that the offending primary molar does not occlude with the opposing arch. In addition, the dental x-ray will be unable to define an intact periodontal ligament. The root surface of the offending primary molar will appear to be confluent with the surrounding alveolar bone. The use of percussion will also indicate that the attachment of the primary molar has a distinct “feel” and a “modified” sound response as compared to a adjoining non-affected molar. A gentle tap with the handle of the mouth mirror will often be a capable diagnostic tool.

Primary Molar Ankylosis — a Review

Early Discovery

During the formative years at UCLA, the Pediatric Dental Department manned a dental clinic in the UCLA Hospital. It occupied a rather small area in the eastern section of the hospital and was staffed two to three days a week. Those first few years found Pediatric Dental Staff completing many exams in support of the Medical Staff and on some occasions they actually performed some ordinary dental procedures.

During that time the staff was able to examine identical twins that presented with a substantial number of missing teeth and ankylosis of primary molars. The concordance pattern was substantial and noted in a paper that was published in the Journal of the Southern California Dental Association. (1)

The authors were unable to get widespread interest and the paper was not widely quoted in subsequent reports related to ankylosis. Although many papers have been written about primary molar ankylosis, this paper was largely overlooked. The concordance pattern is extensive and is shown below.

&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; Twin A

                           Twin A

&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; Twin B

                            Twin B

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 Concordance Pattern Twin A & B

I. Congenitally Missing Permanent Teeth

  1. Maxillary right second premolar tooth # 4
  2. Maxillary right first premolar tooth # 5.
  3. Maxillary left first premolar tooth # 12.
  4. Maxillary left second premolar tooth # 13.
  5. Mandibular left second premolar tooth # 20.
  6. Mandibular right second premolar tooth # 29

Ii. Ankylosed Primary Teeth

  1. Maxillary right first primary molar tooth # B.
  2. Maxillary left first primary molar tooth # I.
  3. Mandibular left second primary molar tooth # K.
  4. Mandibular left first primary molar tooth # L.
  5. Mandibular right first primary molar tooth # S.
  6. Mandibular right second primary molar tooth #T.

III. Non - Formation of Third Molars

  1. No evidence of calcification of the third molars.

IV.  Ectopic Eruption of Maxillary First Molars with Mesial Shift

Concordance

The concordance pattern suggested a genetic etiology and after some additional review in 2015, the authors were able to confirm that most research papers suggest a genetic fault. At this time a Google search of primary molar ankylosis will return 37,300 results in 0.55 seconds.

The current level of interest and the ability of the research community to sequence the genome could present new opportunities for dentistry to employ this emerging science. Over the past few weeks the American Dental Association has announced that they will host a fall conference to explore the opportunities presented in genome sequencing.

Clinical Pathology

While many research papers have attempted to delineate the prevalence of this disorder, the estimates have varied widely from 1% to 16% among those populations studied. Primary molar ankylosis occurs in the younger population with primary teeth that often do not exfoliate at the appropriate time, sometimes causing the permanent bicuspid to erupt out of alignment, and severe cases often require oral surgery and/or orthodontic management. In many cases the costs of oral treatment will require large sums of money to properly manage the pathology.

Figure 2

Figure 2

The diagram above details the mesial movement of the first permanent molar, reducing the arch length and impinging on the mesial-distal distance required for the erupting second bicuspid. This example of arch length loss often requires a substantial amount of orthodontic treatment and surgical intervention. 

The diagram above cannot completely describe the amount of misalignment that can occur in pediatric dental practice. If the ankylosis is severe the eruption of the permanent bicuspids may be completely blocked. In addition the bicuspid may be displaced from its intended location. 

Figure 3 - Ankylosis/Dentigerous Cyst

Figure 3 - Ankylosis/Dentigerous Cyst

Recent Research in Oral Pathology using Genome Sequencing

The most recent research paper that details the genetics of CIPA (Congenital Insensitivity to Pain) also contains an excellent section related to the dental pathology found in this patient. This team of Pediatric Dentists from Xian, China thought it important to add more detail into a report of "Congenital Insensitivity to Pain with Anhidrosis (CIPA)" that has been reported numerous times...but no other researchers carried out any further analysis of the oro-facial defects. (2)

The research article referenced here contains the online version of this important paper. (3) 

Figure 4

Figure 4

Noted in Figure 4 the following:

  1. Many primary teeth missing except lower left 2nd molar...they were loose enough to be extracted by the patient.
  2. Acellular cementum
  3. Periodontal ligament was loosely organized.
  4. Dentinal tubules of greater diameter.
  5. Dentin hypomineralized
  6. Sparse periodontal fibers.
  7. Thinner cementum and fewer attached fiber occupancies.
  8. And more...

NTRK1

NTRK1 is found on the first chromosome, long arm, at 21-22 the notation is 1q21q22. This chromosome has 17 exons and 16 introns with about 25 kilobases of DNA. CIPA has been identified in 60 cases in the U.S. and about 300 worldwide, but only one report (this one) of oral-dental defects...this one article written by Chinese Pediatric Dentists at the Fourth Military Medical University in Xian…the site of the terracotta warriors.(4)

Note the Mutation Analysis of exons 13 and 15 that will predict amino acid substitutions. This patient has two novel missense mutations. This article notes the aplasia of cementum and the lack of periodontal attachment. Keep in mind that the primary first molar begins calcification in the fourth fetal month and the crown is complete by 5.5 to 6 months of age...then the root formation begins.

NTRK1 encodes the receptor tyrosine kinase (RTK) for nerve growth factor (NGF) and is the gene responsible for CIPA. Defects in NGF signal transduction at the TRKA receptor lead to failure to support survival of sympathetic ganglion neurons and nociceptive sensory neurons derived from the neural crest. Thirty-seven different TRKA mutations, identified in patients in various countries, including nine frameshift, seven nonsense, seven splice, and 14 missense mutations, are distributed in an extracellular domain involved in NGF binding, as well as in the intracellular signal-transduction domain.

See: http://www.ncbi.nlm.nih.gov/pubmed/11748840 (4)

On the Move Toward a More Defined Genome

Over the past several years there has been a decided movement toward a better understanding of the human genome as evidenced by the huge strides being made in genomic science. Those strides are exemplified by the delivery of a complete genome taken from archeological sites thousands of years old using newer sequencers that enable quick and reliable assembly of human genetic code. The reduction of the amount of time, effort and expenditure of dollars has created a paradigm shift that has enabled researchers to define the exact nature of past and present gene content.

As the total amount of effort and time required to assemble the gene has improved, so has the ability of researchers to further identify the genetic basis of disease. Are we not entering into a new era that suggests a resurgence of investigation into the genetic basis of disease? If our research dollars can be used more wisely and efficiently, we should be able to characterize the molecular basis of disease in a fashion unheard in past decades. We must adopt a new and intensified effort that harnesses the ability of new sequencers to define and characterize the human genome in the pursuit of the genetic basis of oral pathology. The lassitude that has prevailed as a consequence of high cost has fallen by the wayside as corporate America has unfailingly found quicker and cheaper methods to analyze the human genetic system.

Since one of the objectives of genomic research is to identify the specific etiologic factors that underlie disease, the current ability of modern sequencers to drill down to the smallest units of genetic makeup has created a new desire to define specific disease units.

Ankylosis of Primary Molars – A General Research Plan of Action

Present day standards of genetic analysis have often incorporated the use of Microarray-based Comparative Genomic Hybridization or aCGH. The use of this modality has come into general practice as a method to analyze the genomic status of impaired patients. In that respect, many laboratories have become specialized in their approach to seeking a genetic basis for a specific pathology. In response to the demand for answers, some laboratories have designed their micro-arrays around putative genes…creating a microarray that is more specific in nature. As an example, a specific laboratory might cater to physicians and health workers who are interested in impaired cognitive function. The interested partners of a special needs patient might opt for a genetic profile that seeks to define the etiology of their dysfunction. The assembly of a microarray is therefore based on a specific characterization of genes thought to be involved in that etiology. In this instance the microarray is created for a specific set of genes that might harbor the offending pathology...it is site specific and is titled “targeted.”

If the aCGH is not targeted, it is an array design that looks over the entire genomic sequence, a whole genome or a “shotgun” imperative that seeks to localize the site of a gene malfunction.

If a new study of inquiry was instituted for oral/dental gene malfunction, the use of aCGH to determine copy number variations (CNVs) makes sense because it would deliver an overview of possible areas of interest. This initial characterization of genomic DNA would detail the gains or the losses of whole chromosomes or subchromosomal regions. The use of CGH does allow for the exploration of all 46 chromosomes in a single test and the possible discovery of deletions and duplications. This type of test can also detect single nucleotide polymorphisms or SNPs.

It is apparently true that at some time in the future, a microarray will be custom-created that is “targeted” to specific oro-dental sites. The makeup of such an array will be accomplished when oro-dental implicated genes are more fully identified. Of course, a listing of putative genetic faults that can occur in the oro-dental spectrum is currently available but not yet fully explored.

In the case of Primary Molar Ankylosis, we have many research reports that suggest a genetic etiology, but there is a notable lack of specific papers that seek to directly analyze the genomic status using up-to-date detection methods. Any new movement into the realm of genetic analysis for primary molar ankylosis will likely be based on the creation of an array that is composed of intelligently generated targets.

Our initial efforts now seem to be centered on analysis of the entire genome looking for gains or losses of DNA with a subsequent creation of a targeted array that could define the precise location of primary molar ankylosis. The use of ultra-high density genome-wide oligonucleotide-based microarrays may soon allow the detection of all genomic copy number variations larger than 1 to 10 kb in the human genome. In addition, the possibility that PMA etiology is epigenetic must be taken into account..

Bibliography

1. Stewart, R.E., and Hansen, R.W.: Ankylosis and Partial Anodontia in Twins.  J. So. Cal. Dental Assn. 2:50-52, May 1974

2. Gao L, Guo H, Ye N, Bai Y, Liu X, Yu P, et al. (2013) Oral and Craniofacial Manifestations and Two Novel Missense Mutations of the NTRK1 Gene Identified in the Patient with Congenital Insensitivity to Pain with Anhidrosis.

3.http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0066863 accessed June 14, 2105

4. http://www.ncbi.nlm.nih.gov/pubmed/11748840 accessed June 14, 2015

The "Billowing Skirt" Phenomenon: A Molar Tooth from the Denisova Hominin

The quest for answers about our hominid ancestors took a new twist recently when researchers found two molar teeth and a small finger bone in the Denisova cave in Siberia that allowed the genome characterization of a new hominin that shares a common ancestor with the Neanderthal population.

Additional details of this find were reported in Nature in December of 2010. (Figure 1) This tooth shares no derived morphological features with Neanderthal or modern humans, further indicating that Denisova hominins have an evolutionary history distinct from Neanderthal and modern humans. (1,3)

Figure 1

Figure 1

The characterization of the entire genome of this species was derived from a small piece of the distal phalanx of the pinkie finger and a molar tooth that is at least 30,000-years of age. This tooth is of unusually large proportions as reported by Reich et al. 1

The morphology of this tooth is distinctly different from both Neaderthal and modern humans. In fact the shape of these molar teeth more closely resembles ancient hominins such as Homo erectus or Homo habilis. These molar teeth have been labeled as Denisovan after the name of the Siberian cave in which they were discovered. Even though the exact sequence of the Denisova genome has been described, the anatomic features of these molars await a more complete review in the dental literature. A few digital photographs have been made available that disclose a large number of characteristics that are not seen in dental anatomy textbooks. The most striking feature is the enamel surface that lacks the smooth contours that are seen in modern man.

The enamel surface has a “billowing skirt” look with many rounded segments that do not mimic any modern human molar feature. This morphologic feature may be the result of multi-centric loci of enamel initiation. Since the cusp tip calcification is the initial site for hard tissue formation, numerous enamel calcification sites likely appear in near simultaneous fashion.  (Figure 2)

Enamel Surface

Figure 2 - Distal View

Figure 2 - Distal View

The multi-lobulated nature of the enamel surface is unique to the Denisovan molar and this feature has not been sufficiently characterized. The division between each segment is distinct and presents a picture of independent lobes that are fused vertically. In many of these lobules the occlusal terminus of this segment appears sharpened or reminiscent of the “spiked” look of the buccal cusps of bicuspids and canines. The appearance of the molar in general is one of bulbous refinement characterized by “dagger-like” spikes at uneven intervals around the entire crown. This kind of anatomic feature most likely would improve the penetrating and tearing ability of the molar quadrants. The anatomy appears to favor the tough and often difficult oral management of foods that resist mechanical maceration. (Figure 2)

Root Shape & Angulation

The root shape of this Denisova hominin is somewhat stubby. The long axis of the lingual root is very straight and that root appears to substantially diverge lingually from the long axis of molar. The mesio and disto-buccal roots appear to fall more in-line with the long axis of the tooth. The overall view of the root structure depicts a robust structure with lingual flaring from the long axis.

Cervical Line

The junction of the enamel and the cemental surface creates the cemento-enamel junction (CEJ) that is irregular in its overall distribution. The horizontal axis of the CEJ taken between the mesial and distal points of the CEJ would not intersect the long axis of the tooth at 90 degrees. The description of the CEJ is less uniform than in present-day molar anatomy. (Figure 3)

Crown Anatomy

Figure 3 - Lingual View

Figure 3 - Lingual View

The four cusps of a molar are named the Mesio-buccal (Paracone), the Disto-buccal (Metacone), the Mesio-lingual (Protocone), and the Disto-lingual (Hypocone). As viewed from the lingual aspect, the cusps do not occupy a similar amount of total volume of the crown. The disto-lingual cusp is larger in length and in mesio-distal dimension. That volume discrepancy skews the cemento-enamel junction (CEJ) toward the apex and adds emphasis to the value of that cusp in mastication. This cusp ordinarily occludes with the central fossa of the opposing mandibular molar in a Class I molar relation, thus improving the efficiency of the masticatory process. This emphasis on cuspal size and shape likely improves the quality of the gnathologic interdigitation. The anatomic form of this cusp is in direct relation to its primary role in reducing the fibrous nature of the bolus into a mass that is readily digested by the enzymatic action contained within the oral fluids. The proper introduction of salivary fluid into the bolus does improve the ability of the tissues to acquire adequate amounts of nutrients. Therefore the anatomic emphasis on cuspal form and function does provide a maximum level of nutritive intake. The unusual size and shape of the disto-lingual cusp is indicative of superior masticatory range of function and may provide the highest level of functional dispersion. (Figure 3)

Enamel Depth and Distribution

The enamel depth covering the entire crown is somewhat thinner than might be expected of an early hominid. The protective action of the enamel is not emphasized in this very old molar and likely represents a decreased incremental response to external stimuli that is not currently present in modern human oral structures. The enamel covering is also distributed somewhat differentially as compared to the modern human counterpart. (4)

Figure 4 - Occlusal View

Figure 4 - Occlusal View

Occlusal Surface

The occlusal surface of the other (the second) molar found at the site appears consistent with the anatomic form observed in many modern humans. While its trapezoidal shape is somewhat distinctive, it generally has a form that would not be considered unusual by present-day anatomic standards.

The central fossa is well delineated, as is the distal fossa with a disto-lingual groove. Certainly the lingual cusp (protocone) is easily observed and appears similar is size and volume to current living humans. However, this tooth also displays some of the lobulated features that can be seen in Figure 2.

Pulp Chamber

Using unconventional techniques the pulp chamber of these teeth have been shown to be of very large size. The multifunctional characteristics of the well-vascularized pulp tissue indicate that the molar might react favorably to external stimuli.

For additional data regarding the morphology of the Denisova molar see Supplementary Information 12 contained in reference 1.

Readers may be interested in a 10- minute film produced by the Max Planck Society that features Dr. Bence Viola delivering an overview of the Denisova acquisition. (4)

Figures courtesy Max Planck Institute for Evolutionary Anthropology

 

For further reading

1. Genetic history of an archaic hominin group from Denisova Cave in Siberia.

Reich D, Green RE, Kircher M, Krause J, Patterson N, Durand EY, Viola B, Briggs AW, Stenzel U, Johnson PL, Maricic T, Good JM, Marques-Bonet T, Alkan C, Fu Q, Mallick S, Li H, Meyer M, Eichler EE, Stoneking M, Richards M, Talamo S, Shunkov MV, Derevianko AP, Hublin JJ, Kelso J, Slatkin M, Pääbo S.

Nature. 2010 Dec 23; 468(7327):1053-60. Department of Genetics, Harvard Medical School, Boston, Massachusetts 02115, USA. See: http://www.nature.com/nature/journal/v468/n7327/abs/nature09710.html

2. http://www.ncbi.nlm.nih.gov/pubmed/21179161 (Resourced in July2013)

3. http://en.wikipedia.org/wiki/Denisova_hominin (Resourced in July 2013)

4. http://www.youtube.com/watch?v=eweVB0XPC_8

 

Estimating the ANB angle of Homo Naledi

Introduction

The Homo Naledi hominin was discovered in the Dinaledi Chamber of the Rising Star cave system in South Africa in 2013. This recent find has created “a stir” among fossil hunters who have named their find Homo naledi. The skull reproduced below has not been age dated as yet, but the recovery team indicates that dating will occur some time in the near future. Speculation has placed the date of this find at possibly less than one million years. It appears that H. Naledi is one of our more recent cousins.

The Site

The cave system is located in the Cradle of Humankind World Heritage Site, Gauteng Province, South Africa a short distance north and west of Johannesburg, Africa. The oro-dental remains include 137 isolated dental specimens and an additional 53 teeth that were found in mandibular or maxillary bone specimens. The researchers have not identified specific primary teeth found at the site...only a reference to their presence. Additional studies of the primary dentition must await further analysis of the dental remains.

See: https://en.wikipedia.org/wiki/Rising_Star_Cave

 

The Rising Star Cave,&nbsp;Figure courtesy of the National Geographic Society

The Rising Star Cave, Figure courtesy of the National Geographic Society

See: http://news.nationalgeographic.com/2015/09/150910-human-evolution-change/

Estimating the ANB angle

At first glance of the full scale rendering of the skull in the October 2015 edition of National Geographic depicts a very prominent mandible with a surprising amount of negative ANB measurement. Present day human cephalograms taken for potential orthodontic treatment often suggest that the angle ANB should have a mean of a plus two degrees in the Caucasian race. The ANB of the above referenced skill was calculated in a non-scientific manner and resulted in a measurement of a minus six degrees, a difference of eight degrees from the Caucasian mean. The vary large discrepancy between Homo sapiens and Homo nalendi is extreme and dramatically demonstrates the prognathic nature of this newly discovered early hominid. (1)

Mandibular Form

An occlusal view of the mandibular shape depicts a parabolic shape with the greatest width at the second molar area. The third molars are positioned somewhat to the lingual, creating an overall ovoid shape. This continuation of the ovoid shape distal to the first molars is unique in relation to present day posterior quadrant morphology. 

The cephalometric points are defined as “A” point, the indentation of the maxilla above the maxillary incisors, “N” or Nasion as the junction of the nasal bone and the maxilla, and “B” point as the indentation just below the apex of the mandibular incisor.

&nbsp;Homo Naledi

 Homo Naledi

The following quote is taken from the elifesciences.org website referenced below.

“Aside from these limited faunal materials, the Dinaledi collection is entirely composed of hominin skeletal and dental remains. The collection so far comprises 1550 fossil hominin specimens, this number includes 1413 bone specimens and 137 isolated dental specimens; an additional 53 teeth are present in mandibular or maxillary bone specimens. Aside from the fragmentary rodent teeth, all dental crowns (n = 179) are hominin, recovered both from surface collection and excavation. Likewise, aside from the few bird elements, all morphologically informative bone specimens are clearly hominin. In all cases where elements are repeated in the sample, they are morphologically homogeneous, with variation consistent with body size and sex differences within a single population. These remains represent a minimum of 15 hominin individuals, as indicated by the repetition and presence of deciduous and adult dental elements.”

This quotation mentions the presence of primary (deciduous) dental elements but does not directly identify which teeth have been found. The characterization of the permanent teeth is very complete, but any description of primary teeth mentioned within the context of the submission is lacking. So, for now Pediatric Dentists and others will need to rely on a further examination of the recovered skeletal elements to ascertain the character of the primary dentition.

 

Figure 2&nbsp;

Figure 2 

Illustration “H”in Figure 2 depicts a mandibular form that markedly varies from modern human mandibular shape. The illustration includes the third molars and they are placed somewhat lingual to the mandibular second molars.  Illustration “G” is the basis of the National Geographic composite comparing brain case size of Homo naledi with a modern human skull.

For additional information see: http://dx.doi.org/10.7554/eLife.09560.019

Figure 3 

Figure 3

 

The elongated talonid cuspal morphology of the posterior quadrants illustrates a common feature found on the mandibular bicuspids. This unusual form suggests that masticatory function may be improved when the cuspal form is able to penetrate a tenacious bolus of food. The pointed character of the bicuspids and molars are most visible in “B” of Figure 3.

Primary Teeth Primary (deciduous) teeth were noted in the original article, and any explanation of their number of description is lacking.

For further information on Figure 3 see: http://dx.doi.org/10.7554/eLife.09560.007

Bibliography

Reference 1 http://elifesciences.org/content/4/e09560#sthash.qsRL0ZZe.dpuf accessed September 30, 2015

Reference 2 The Journal of the National Geographic Society, October 2015 See: voices.nationalgeographic.com

Oral Pathology and CRISPR-Cas9

With the arrival of a system to edit the DNA using CRISPR (clustered regularly-interspaced short palindromic repeats), the dental community has suddenly found themselves entwined in a new set of imponderables. The profession may have been sitting back wondering what could be done to give their patients a modified genetic profile. Many of us observed that an oral-facial defect of genetic etiology was beyond real help. We had no capacity to modify a genetic defect but we often used the old “work around” to mount a treatment plan that alleviated the problem.

The profession is aware of the large number of genetic faults that occur in and around the facial structures. Our response was often one of inaction because we were not able to adopt any treatment plan that approached some finality of outcome.

This week Time magazine reminded us once again that the CRISPR-Cas9 is challenging the very nature of our being. They report that Kathy Niakan of the Crick Institute in London has been granted the right to use this emerging technology on a viable human embryo…an astonishing fact that brings to mind some of the most memorable announcements in medicine over the past many decades.

While CRISPR-Cas9 has been researched in animals since 2012, its use on human tissue has taken a back seat as the methodology has matured. Now Time magazine considers the CRISPR-Cas9 technique to be “precise, efficient, affordable and easy to use.”

Many of our dental colleagues have suggested that our interest in the etiology of genetic-based oral anomalies makes little difference if we cannot change the human genome. But now we are faced with an exciting challenge…find the offending gene and manipulate the genetic structure to produce a normal genome sequence.

This author has advocated a change in our “mind set.” We must look closely for a genetic fault in Primary Molar Ankylosis. It seems only a matter of time that our profession will be able to identify the causative genes in many oral pathologies. If the research laboratory can tell us which genes are at fault for a specific disorder, we may find that in the near future a CRISPR solution to the fault can revise the genetic structure of the genome…a thought that was inconceivable until just recently.

The old“hack” that suggests we overlook some genetic faults since we cannot change the gene may be “out of date.” Oral pathology may have a new beginning...starting this year, an outlook that supersedes our “status quo” and delivers to our profession a new window on treatment procedures that were once deemed to be impossible.

Will we someday provide the missing or extra gene/epigene that causes Primary Molar Ankylosis using CRISPR-Cas9 technology?

Ankylosis of Primary Molars – Seeking an Answer

Recent Research Review

“Epigenetic Marks Define the Lineage and Differentiation Potential of Two Distinct Neural Crest-Derived Intermediate Odontogenic Progenitor Populations" (Gopinathan G et al)

       The etiology of primary molar ankylosis has eluded the profession for many decades. While the elusive nature of this pathology has continued to plague the Pediatric Dentist and others, some remarkable research has appeared recently that opens new avenues for discussion.

        This review is based on the bibliographic reference given below as well as some related papers from the same laboratory.

        This research team is headed by Dr. Thomas Diekwisch et al who until recently was the first director of the Brodie laboratory for Craniofacial Genetics and the Allan G. Brodie Endowed Chair. His research at the University of Illinois focuses on stem cells and epigenetic control of pluripotency by the chromatin remodeling factor CP27. Dr. Diekwisch is currently on the faculty of Baylor College of Dentistry at Baylor, Texas.

        This laboratory uses tissue culture technology to redefine the roles played by dental pulp (DP) and dental follicle (DF) progenitors cells that are ultimately responsible for other dental tissues.

        In his abstract we quote, “Epigenetic mechanisms, such as histone modifications, play an active role in the differentiation and lineage commitment of mesenchymal stem cells. In the present study, epigenetic states and differentiation profiles of two odontogenic neural crest-derived intermediate progenitor populations were compared: dental pulp (DP) and dental follicle (DF).”

        Later in the abstract he continues, “the present study indicates that the DF intermediate odontogenic neural crest lineage is distinguished from its DP counterpart by epigenetic repression DSPP and DMP 1 genes and through dynamic histone enrichment responses to mineralization induction. Findings presented here highlight the crucial role of epigenetic regulatory mechanisms in the terminal differentiation of odontogenic neural crest lineages.”

        Another quote completes the theme of which progenitor cells are involved in tooth formation.  “dental papilla progenitors differentiate into dental pulp (DP) and odontoblasts, which in turn secrete tooth dentin, while (DF) progenitors migrate extensively and eventually form periodontal ligament (PDL), alveolar bone (AB), and root cementum (CEM). The terminal differentiation of these intermediate progenitors into DP odontoblasts, tooth dentin, and cells and tissues of the periodontal apparatus is controlled by both genetic and epigenetic factors.

        Mesenchymal cells are the progenitors of dental tissues. As the title suggests, the final form of dental tissues is the result of epigenetic marks.

        These mechanisms are the result of histone modifications that play a role in the differentiation and lineage commitment of mesenchymal stem cells. This translational research appears to have unusual merit since it aligns current thinking about the etiology with solid research protocols. Dr. Diekwisch and his colleagues sought to distinguish the roles that are played by DP cells and the cells of the DF cells in culture.

 

Bibliography

        1. Gopinathan G, Kolokythas A, Luan X, Diekwisch TGH. Epigenetic marks define the lineage and differentiation potential of two distinct neural crest-derived intermediate odontogenic progenitor populations. Stem Cells Dev. 2013;22(12):1763–78. doi:10.1089/scd.2012.0711.

         2. Kangaria SJ, Y Ito, X Luan and TG Diekwisch. (2011). Differentiation of neural-crest-derived intermediate pluripotent progenitors into committed periodontal population involves unique molecular signature changes, cohort shifts, and epigenetic modifications. Stem Cells Dev 20:39-52.

 

A Proposed Primary Molar Ankylosis Foundation

For many decades the Pediatric Dental community has sought to ameliorate the “bone to bone” attachment of some primary teeth to the alveolar process. These teeth do not possess a normal attachment to the jaw bone and often do not exfoliate at the appropriate age. The creation of a Foundation to monetarily support research and development of treatment possibilities remains one of the most important steps to be taken in the remediation of this pathology.

What is ankylosis?

Who does it strike?

What are the downstream consequences?

Is there a congenital component?

What is the treatment? How delivered?

Research directions and support

Treatment support. Specialized centers for treatment., follow up

Establishment of a central processing body…a Foundation?

Obtaining monetary support

Extent of the oral pathology. Size of the problem?

Create a research center at a major university dental school?

Creation of a guiding panel of experts?

Obtaining seed dollars to begin organizational efforts.

A Review of Ankylosis in Monozygotic Twins

A Review of Ankylosis in Monozygotic Twins

Helpin ML, Duncan WK. Ankylosis in monozygotic twins. ASDC J Dent Child 1986;53:135-139.

Helpin Twin DHH

Helpin Twin DHH

Helpin Twin HDH

Helpin Twin HDH

This blog entry is a review of the article that appeared in the ASDC Journal in 1986. It contains some interesting facts that illustrate the pathology that often surrounds ankylosis. The twins have multiple missing permanent teeth and some variation in the location of ankylosis. Each twin has several differences in the location of missing permanent teeth and differences in ankylosed primary molars. A comparison of each panoramic x-ray points out the dissimilarities of the inheritance pattern. The monozygous nature of the twins as reported indicates that the oral structures do not fall into common ground. This blog also details the “Ankylosis and Partial Anodontia in Twins”, indicating that the oral structures are very similar if not identical. In a real sense we have observed differing patterns of odontogenesis in identical twins more than once. The mandibular dentition on each twin is near identical. The primary molar #T is present in rudimentary form indicating that the osteoclasts have engulfed much of the hard structure. In the maxillary arch there are several differences shown in the concordance pattern. The etiology of this patterning in oral development stands out as a dissonance in oral development in monozygotic offspring. Perhaps incomplete penetrance could explain the difference, but are we observing another more recent explanation…epigenetics. Review in this blog “Ankylosis of Primary Molars – Seeking an Answer.”

Concordance Pattern for Twins DHH/HDH

Key

CM = Congenitally Missing

EX = Exfoliated

Bold Face = Discordant

Tooth Number Twin DHH/HDH

1 Excluded/ Excluded

2 CM/ CM

3 Present/ Present

4 CM/ CM

5 CM/ Present

6 CM/ CM

7 CM/ Present

8 Present/ Present

9 Present/ Present

10 CM/ Present

11 CM/ CM

12 Present/ Present

13 CM/ CM

14 Present/ Present

15 CM/ CM

16 Excluded/ Excluded

17 Excluded/ Excluded

18 CM/ CM

19 Present/ Present

20 CM/ CM

21 Present/ Present

22 Present/ Present

23 Present/ Present

24 Present/ Present

25 Present/ Present

26 Present/ Present

27 Present/ Present

28 Present/ Present

29 CM/ CM

30 Present/ Present

31 CM/ CM

32 Excluded/ Excluded

Primary Teeth

A Ankylosed/ Ankylosed

B Ankylosed/ Missing (radiolucency)

C Present/ Present

D Present/ Present

E EX/ EX

F EX/ EX

G EX Present

H EX/ EX

I EX/ EX

J Ankylosed/ Ankylosed

K Ankylosed/ Ankylosed

L EX/ EX

M EX/ EX

N EX/ EX

O EX/ EX

P EX/ EX

Q EX/ EX

R EX/ EX

S EX/ EX

T EX/ Ankylosed

Identical Twins and “Oral Epigenetic Loading”

In this blog there are two submissions that address the nature of ankylosis of primary molars combined with hypodontia. Compare the panoramic x-rays of two sets of “identical twins” who exhibit disparate features in their oral anatomy. It seems difficult to grasp how two sets of twins with anatomical differences can be identified as “identical.” Our common sense tells us that identical means the same…and yet we observe enormous disparities between each set of twins.

See in this blog two submissions for comparison.

Primary Molar Ankylosis - A Review

A Review of Ankylosis in Monozygotic Twins

A review of each blog would indicate that the “identical” twins may not be identical in oral features considered to be heritable. Is it possible that one set of twins carries added features in the genome that are not identifiable using current genome sequencing techniques? If each twin were sequenced would the genome be identical? If so, then we must conclude that one of the sets of twins carries some additional “signals” that direct the formation of the periodontal ligament or the initiation of a permanent tooth follicle. If an identical twin has 10 to 16 discordant oral anatomical features, then we might surmise that they are different in some genetic fashion either heritable or non-heritable. Taken at face value, the variance between identical twins at the oral level creates the thought that there must be another factor that is operative. First thought might implicate epigenetics, a feature that has been explored at the cellular level of tooth formation. If the differences between two identical twins result in differing levels of oral development, including anodontia, ankylosis and a variety of other oral manifestations, can we then declare that they have a variety of oral epigenetic loading?

Oral Pathology and CRISPR-Cas9

With the arrival of a system to edit the DNA, the dental community has suddenly found themselves entwined in a new set of imponderables. The profession may have been sitting back wondering what could be done to give their patients a modified genetic profile. Many of us observed that an oral-facial defect of genetic etiology was beyond real help. We had no capacity to modify a genetic defect but we often used the old “work around” to mount a treatment plan that alleviated the problem.

The profession is aware of the large number of genetic faults that occur in and around the facial structures. Our response was often one of inaction because we were not able to adopt any treatment plan that approached some finality of outcome.

This week Time magazine reminded us once again that the CRISPR-Cas9 is challenging the very nature of our being. They report that Kathy Niakan at the Crick Institute in London has been granted the right to use this emerging technology on a viable human embryo…an astonishing fact that brings to mind some of the most memorable announcements in medicine over the past many decades.

While CRISPR-Cas9 has been researched in animals since 2012, its use on human tissue has taken a back seat as the methodology has matured. Now Time magazine considers the CRISPR-Cas9 technique to be “precise, efficient, affordable and easy to use.”

Many of our dental colleagues have suggested that our interest in the etiology of genetic-based oral anomalies makes little difference if we cannot change the human genome. But now we are faced with an exciting challenge…find the offending gene and manipulating the genetic structure to produce a normal genome sequence.

This author has advocated a change in our “mind set.” We must look closely for a genetic fault in Primary Molar Ankylosis. It seems only a matter of time that our profession will be able to identify the causative genes in many oral pathologies. If the research laboratory can tell us which genes are at fault for a specific disorder, we may find that in the near future a CRISPR solution to the fault can revise the genetic structure of the genome…a thought that was inconceivable until just recently.

The old “hack” that suggests we overlook some genetic faults since we cannot change the gene may be “out of date.” Oral pathology may have a new beginning...starting this year, an outlook that supersedes the
“status quo” and delivers to our profession a new window on treatment procedures that were once deemed to be impossible.

In our lifetime will we observe oral genetic anomalies corrected using CRISPR-Cas9 technology? What…What…What, a research tool that completely overturns our ideas of disease and how it is treated? A basic revision of our textbooks, a redo of drug therapies based on genetic structure, a modification of medicine at its very core…astounding!
Send me back to Dental School!

The Caiman Periodontium – A Review with a Guess

The Caiman Periodontium – A Review with a Guess

Human primary molars that are histologically attached to the alveolar bone are noted to be ankylosed. The teeth of many fish and reptiles are also attached to the alveolar bone and are also found to be ankylosed or fused to the alveolar process.
In the study reported by Thomas Diekwisch et al in 2002 we note that the authors have studied the periodontal histologic features of the Gecko (Hemidacylus turcicus), juvenile Caiman (Caiman crocodilus crocodilus), and the Swiss-Webster mouse (Mus musculus).
The Caiman was found to present with an intermediary form of periodontal ligament (PDL) between the mouse and the gecko…a form that was composed of a mineral free mouse ligament and the mineralized gecko PDL. The Caiman Hertwig’s epithelial root sheath (HERS) was perforated in similar fashion as compared with the mouse PDL. In addition, HERS covered the entire root surface of the Caiman and mouse model. In the gecko the HERS was found only on the coronal portion of the root surface. This blogger notes that the HERS is perforated in the mouse and very different from the continuous HERS of the gecko model…suggesting that the HERS plays a distinct role in the ankylosis to gomphosis continuum.

The casual observer might suggest that HERS plays an important role in the development of primary molar ankylosis.
The time frame of this pathology spans a period that approximates 2 years and 2 months in human oral development. Over this time period HERS may play a major role in the final outcome of the PDL attachment since the anatomic differences between the three models indicate that the HERS is histologically variant.
This blogger also suspects that primary molar ankylosis is controlled by stochastic epigentic mechanisms that are highly conserved and likely heritable.

Bibliography

Caiman periodontium as an intermediate between basal vertebrate ankylosis-type attachment and mammalian “true” periodontium
James E. McIntosh, Xochitl Anderton, Lavinia Flores-De-Jacoby, ,David S. Carlson, Charles F. Shuler and Thomas G.H. Diekwisch
Article first published online: 11 NOV 2002
DOI: 10.1002/jemt.10222

Caiman

Caiman

Gecko

Gecko

Evidence of Handedness in Homo habilis

Any previous bias against left-handers may date back much earlier in human history that previously believed. This blogger likes the left-handed pitchers of baseball and loves to watch them pitch, but they may have been in the minority as suggested by this posting.

The Smithsonian magazine has again struck “dental cord” when they published an article showing the earliest evidence of right-handedness in the fossil record. Lead investigator David Frayer at the University of Kansas is the author of this investigation titled “Study finds earliest evidence in fossil record for right-handedness.”

The study is published in the Journal of Evolution and reveals striations on the labial surface (occlusal) of Homo habilis that were derived from a cutting motion across the surface of the incisor teeth to detach meaty foods by cutting with sharp stone tools.  The striations are distinct and represent directional marks that indicate right-handedness.

According to David Frayer, handedness and language are controlled by different genetic systems that originate from the left side of the brain.

 

a. Occlusal of Maxillary arch of Homo habilis 1.8 million years.b. Frontal view of the maxilla.c. Labial view of maxillary incisors.

a. Occlusal of Maxillary arch of Homo habilis 1.8 million years.

b. Frontal view of the maxilla.

c. Labial view of maxillary incisors.

Frayer said "that the striations were found only on the labial surface of the incisors and that they veered from left down to the right, indicating right-handedness in Home habilis...an astonishing revelation for dental practitioners who will likely view this research as highly remarkable. The extreme occlusal wear is common in skeletal material of this early age, but the definition of striations on the labial surface might encourage other anthropologists to view more closely the labial features of other anthropologic specimens.

This review taken from "Study finds earliest evidence in fossil record for right-handedness"

Teeth striations of Homo habilis fossil date bace 1.8 million years

Bibliography

Clarke, R.J., Fiore, I., Bondioli, L., Blumenschine, R. J., Perez-Perez, A., Martinez, L.M., Estebaranz, F. 2016 Journal of Human Evolution 100:65-72