Wednesday, April 30, 2014

Trico-Dento-Osseous Syndrome

Trico-Dento-Osseous Syndrome
Resident: Margaret Maclin

Definition: Tricho-Dento-Osseous (TDO) syndrome is an autosomal dominant genetic disorder that belongs to the group of diseases known as ectodermal dysplasias. It derives its name from the three primarily affected tissues including hair, teeth and bone.

Etiology: It is caused by a DLX3 gene mutation and is passed in an autosomal dominant inheritance pattern. 

Clinical Features: TDO syndrome is characterized by kinky or curly hair; poorly developed tooth enamel; and unusual thickness and/or denseness (sclerosis) of the top portion of the skull (calvaria) and/or the long bones. In some cases, affected individuals also exhibit abnormally thin, brittle nails or premature fusion of the fibrous joints between certain bones in the skull (craniosynostosis), causing dolicocephaly. Kinky, course and/or curly hair is present at birth in 80% of people with TDO. Only 46% of the individuals with TDO and kinky, course and/or curly hair at birth retain this phenotype after infancy. There is an increased cranial thickness. The loss of visible mastoid pneumatization is the most common osseous feature seen in affected individuals (82%) and is relatively uncommon in unaffected people (8%).

Oral Manifestations: While all individuals with TDO appear to have enamel hypoplasia and taurodontism, the expression of these traits is highly variable. The teeth appear discolored in 76% of the affected individuals while the remaining affected individuals have teeth of normal color. Enamel alteration in people with TDO ranges from being extremely thin and/or rough and pitted to being of normal color and only slightly decreased thickness.

Treatment: Symptomatic.

Dental Considerations: Treatment depends on severity of defects and esthetic demands of patient and may include full coverage restorations.

Lesch-Nyhan Syndrome

Lesch-Nyhan Syndrome
Resident: Margaret Maclin

Definition: Lesch-Nyhan syndrome is an inheritable disorder that affects how the body builds and breaks down purines.

Etiology: inherited as an X-linked trait (1/3 of cases are de novo). It mostly occurs in boys. Persons with this syndrome are missing or are severely lacking an enzyme called hypoxanthine-guanine phosphoribosyltransferase 1 (HGP). The body needs this enzyme to recycle purines. Because of the deficiency in HGPRT, abnormally high levels of uric acid build up in all body fluids.

Frequency: about 1 in 380,000 people. Usually boys, a few cases worldwide have been reported in girls.

Clinical Features: The excess uric acid levels cause children to develop gout-like swelling in some of their joints. In some cases, kidney and bladder stones develop because of the high uric acid levels. Males with Lesch-Nyhan have delayed motor development followed by bizarre, sinuous movements and increased deep tendon reflexes. A striking feature of Lesch-Nyhan syndrome is self-destructive behavior characterized by chewing off fingertips and lips, if not restrained that begins in the second year of life. It is unknown how the enzyme deficiency causes these problems.

Oral Manifestations: The most typical feature results in partial or total destruction of perioral tissues.

Treatment: There is no cure for LNS, however there are new experimental treatments to alleviate symptoms. Gout can be treated with allopurinol to control excessive amounts of uric acid. Kidney stones may be treated with lithotripsy, a technique for breaking up kidney stones using shock waves or laser beams. There is no standard treatment for the neurological symptoms of LNS. Some may be relieved with the drugs carbidopa/levodopa (used to treat Parkinson's disease), diazepam, phenobarbital, or haloperidol (antipsychotic).

Dental Considerations: A soft mouthguard fabricated to prevent the destruction of perioral soft tissues and combined psychiatric pharmacologic therapy proved to have satisfactory results. In extremem cases, teeth may need to be extracted.

Prognosis: The outcome is likely to be poor. Persons with this syndrome usually require assistance walking and sitting and generally need a wheelchair to get around. Death is usually due to renal failure in the first or second decade of life, though more cases are being reported of patients living well into adulthood.

Tuesday, April 29, 2014


Resident: Avani Khera


Overview: A rare and sometimes fatal metabolic bone disease.


-Mutations in the liver/bone/kidney alkaline phosphatase gene (ALPL) encoding the tissue-nonspecific alkaline phosphatase (TNAP)

- Autosomal recessive disorder


-The pathognomonic symptom is subnormal serum activity of alkaline phosphatase (ALP). 

Oral manifestations:

- Early loss of deciduous dentition with root intact

- Little cementum produced

-odontohypophosphatasia-premature exfoliation of fully rooted primary teeth (anterior deciduous teeth most often affected) and/or severe dental caries, often not associated with abnormalities of the skeletal system. Reduced alveolar bone, enlarged pulp chambers and root canals. Odontohypophosphatasia should be considered in any patient with a history of early unexplained loss of teeth or abnormally loose teeth on dental examination.

Clinical manifestations:

- Symptoms are highly variable: ranges from stillbirth without mineralized bone to early loss of teeth without bone symptoms

Special dental considerations/needs:

- Early loss of deciduous dentition with root intact


-Current management consists of palliating symptoms, maintaining calcium balance and applying physical, occupational, dental and orthopedic interventions as necessary.

Rubenstein-Taybi Syndrome – aka Broad Thumb-Hallux Syndrome

Overview: This is a condition characterized by short stature, learning difficulties, broad thumbs and first toes.


- Autosomal dominant inheritance pattern

- Many times it occur de novo

- 1 in 125,000-300,000

Oral manifestations:

- Manifestations associated with leukemia, lymphoma, and tumors

Clinical manifestations:

- Broad Thumbs and first toes

- Small height, bone growth

- May have cardiac issues

- May be overweight and have short attention span

- Increase risk of leukemia, lymphoma, and tumors

Special dental considerations/needs:

- Anesthesia may be contraindicated in these patients because of respiratory distress, cardiac arrythmias

DeLange Syndrome

Resident: Hofelich

  • genetic disorder present from birth, but not always diagnosed at birth
  • affects both genders equally
  • 1 in 10,000 live births
  • range from mild to severe
  • mutations in the NIPBL, SMC1A, and SMC3 genes
  • >50% - NIPBL gene mutations
  • proteins produced from all three genes play important roles in directing development before birth
    • these proteins help regulate the structure and organization of chromosomes and are involved in the repair of damaged DNA
    • regulate the activity of certain genes in the developing limbs, face, and other parts of the body
  • mutations disrupt gene regulation during critical stages of early development
  • studies suggest that SMC1A and SMC3 gene mutations tend to cause somewhat milder signs and symptoms than those seen with mutations in the NIPBL gene
  • ~35% - cause is unknown
  • when caused by mutations in the NIPBL or SMC3 gene - autosomal dominant pattern of inheritance
  • caused by SMC1A mutations - X-linked pattern of inheritance
  • almost all occur with no family history
  • slow growth before and after birth
  • intellectual disability that is usually severe to profound
  • skeletal abnormalities involving the arms and hands
    • small hands and feet
    • incurved fifth fingers (clinodactyl)
    • partial joining of the second and third toes
    • proximally placed thumbs
    • missing fingers, hands or forearms
  • distinctive facial features
    • arched eyebrows that often grow together in the middle (synophrys)
    • long eyelashes
    • low-set ears
    • small, widely sa\paced teeth
    • small, upturned nose
    • thin, downturned lips
  • behavior problems similar to autism, self-injurous behavior, OCD
  • hypertrichosisqa
  • microcephaly
  • hearing loss
  • short stature
  • GERD (~85%)
  • Eye ailments such as blepharitis (inflammation of the eyelid), faulty or nonexistent tear ducts, ptosis (droopy lids), and extreme nearsightedness (myopia) can occur
Dental Considerations
  • small jaw
  • poor oral hygiene
  • crowded teeth
  • small teeth
  • periodontal disease
  • erosion of teeth caused by reflux
  • cleft palate is common

Beckwith-Wiedemann Syndrome

Resident: Hofelich
  • classified as an overgrowth syndrome
  • affected infants are considerably larger than normal (macrosomia) and continue to grow and gain weight at an unusual rate during childhood
  • growth begins to slow by about age 8
  • adults with this condition are not unusually tall
  • hemihyperplasia - specific parts of the body may grow abnormally large, leading to an asymmetric appearance
  • estimate:1 in 12,000 newborns  (may actually be more common because some people with mild or unusual symptoms are never diagnosed)
  • abnormal regulation of genes in a particular region of chromosome 11 (abnormalities in chromosome 11 that undergo genetic imprinting (ICRs) are responsible for most cases of BWS)
  • at least half of all cases are due to methylation
    • ICRs control the methylation of several genes that are involved in normal growth, including the CDKN1C, H19, IGF2, and KCNQ1OT1 genes. Abnormal methylation disrupts the regulation of these genes, which leads to overgrowth and the other characteristic features of BWS
  • 10-20% of cases are caused by a genetic change known as paternal uniparental disomy (UPD) 
    • paternal UPD causes people to have two active copies of paternally expressed imprinted genes rather than one active copy from the father and one inactive copy from the mother
    • people with paternal UPD are also missing genes that are active only on the maternal copy of the chromosome
    • paternal UPD usually occurs early in embryonic development and affects only some of the body's cells (mosaicism). Mosaic paternal UPD leads to an imbalance in active paternal and maternal genes on chromosome 11
  • Less commonly caused by mutations in the CDKN1C gene
    • provides instructions for making a protein that helps control growth before birth.
    • mutations prevent this protein from restraining growth
  • ~ 1% have a chromosomal abnormality such as a translocation or duplication of genetic material from chromosome 11
  • ~10-15% of people with BWS are part of families with more than one affected family member
    • condition appears to have an autosomal dominant pattern of inheritance in these families
  • ~85% of people with BWS are the only person in their family that has been diagnosed with the condition
  • large birth weight and length
  • hypoglycemia in the newborn
  • marcroglossia
  • malocclusion
  • omphalocele
  • hemihyperplasia/hemihypertrophy
  • ear grooves or pits
  • nevas flammeus ("stork bite")

  • Kidney related issues
    • Wilm's Tumor
    • Medullary Sponge Kidney
    • Diabetes Insipidus
  • Increased risk of cancerous and noncancerous tumors
    • occurs in ~10% and almost always during childhood
    • Wilm's Tumor
    • rhabdomyosarcoma
    • hepatoblastoma
  • ~ 1 in 5 dies early in life

Monday, April 28, 2014

Dentinogenesis Imperfecta and Dentin Dysplasia

Dentinogenesis Imperfecta
- anomaly of structure - histodifferentiation
- heritable defect of predentin matrix
- normal mantle dentin
- amorphic and atubular circumpulpal dentin
- 1:8000
- Autosomal dominant

Three Types:
1. DI Shields Type I
            - occurs with osteogenesis imperfecta type
            - primary teeth more severely affected
            - permanent teeth most affected – central incisors and 1st
            - amber translucence
            - periapical radiolucencies
            - bulbous crowns, obliteration of pulp chambers, root
            - rapid attrition of teeth

2. DI Shield Type II
            - occurs alone – no OI; aka “hereditrary opalescent dentin”
            - both dentitions affected equally
            - same characteristics of DI-I
            - irregular or tubular pattern
            - rapid attrition

 3. DI Shields Type III
            - rare – Brandywine population only (tri-racial isolated
   in Maryland)
            - bell-shaped crowns
            - shell teeth with short roots and enlarged pulp chambers
            - multiple pulp exposures
            - regular tubules
            - enamel pitting

            - different expression for the same DI-II gene

Dentin Dysplasia
-   anomaly of dentin structure
-   autosomal dominant dental condition that is more rare than Dentinogenesis
- characterized by presence of normal enamel but atypical dentin with abnormal
  pulpal morphology
-   Incidence: 1:100,000

Two Types:
1. Shields Type I Dentin Dysplasia = Radicular Dentin Dysplasia
            - normal color of crown of primary and permanent teeth
            - short, blunted roots or rootless in both dentitions
            - obliterated pulp chambers
            - periapical radiolucencies
            - cascading of dentinal tubules in root
            - can be normal tubule orientation in coronal of normal
            - root sheath problem
       - severe mobility and malalignment
       - autosomal dominant
       - normal dentinal tubule formation is blocked and new
         dentin forms around obstacles

2. Shields Type II Dentin Dysplasia = Coronal Dentin Dysplasia
            - primary teeth affected
            - coronal dentin is involved as well as root dentin
            - amber colored primary teeth
  - permanent teeth look normal, but radiographically   
   demonstrate thistle-tube shaped pulps and multiple pulp