Wednesday, April 25, 2012

Williams Syndrome

Williams Syndrome

Rare genetic development that can lead to developmental problems

Rare genetic disorder caused by missing genes. A person with Williams syndrome has a 50% chance of passing on the syndrome to their children. Occurs in 1:8,000 births.

Diagnosis not always made at birth. Signs and symptoms can lead to blood work and genetic testing to determine diagnosis.

Clinical Features:
Systemic/medical conditions associated: Delayed speech that may later turn in strong speaking abilities. Developmental delays, easily distracted, ADD, feeding problems, clinodactyly or inward bend of the small finger, learning disorders, and mild to moderate mental disabilities. Personality traits include being very friendly, trusting strangers and interested in music. Short stature and sunken chest. Medical conditions include aortic stenosis, pulmonary stenosis. High blood pressure and hypercalcemia which may cause seizures.

Facial features: Flatterned nasal bridge with upturned nose, prominent lips with open mouth, epicanthal folds

Oral manifestations: partially missing teeth, defective tooth enamel or small widely spaced teeth.

Dental Considerations:
Early treatment and prevention for those with defective tooth enamel. Making patient comfortable, non stress inducing appointment due to poor heart condition and blood pressure. General Anesthesia is more risky in these patients because of these conditions.

Recent information:
Avoid taking extra calcium and vitamin D. Physical therapy and speech therapy is important for these patients.

Hurler Syndrome

Hurler Syndrome

-AKA muciopolysaccharidosis.
-Genetic disorder that results in the buildup of glycosaminoglycans.

Results in the buildup of glycosaminoglycans due to a deficiency of alpha-L iduronidase. A buildup of heparan sulfate and dermatan sulfate occurs. Occurs in 1:25,000 births.

Prenatal diagnosis with amniocentesis and chorionic villus sampling can verify if a fetus either carries a copy of the defective gene or is affected with the disorder. After birth of a child clinical examination and urine tests are used.

Clinical Features:
Systemic/medical conditions associated: Progressive deterioration, hepatosplenomegaly, dwarfism and unique facial features. Mental retardation is progressive with death occurring by age 10. Language may be limited due to hearing loss and enlarged tongue. Corneas become clouded and retinas begin to degenerate. Carpal tunnel syndrome and restricted joint movement is common. Children may be large at birth with hernias. Many children slow in growth after age three develop a short body trunk and grow to less than 4 feet. Liver spleen and heart are often enlarged. Feeding often difficult and many children die early from obstructive airway disease, respiratory infections or cardiac complications.

Facial features: Flat face, depressed nasal bridge and bulging forehead.

Dental Considerations:
-Prevention and often and early treatments to prevent stressful and lengthy appointments.
-Monitor for obstructive airway when performing dental treatment.

Recent information:
Gene therapy has gained much interest. Patients are given retroviral, lentiviral, AAV and even nonviral vectors to deliver the iduronidase gene. This treatment has been successful on mice, dogs and cat models.

Goldenhar Syndrome

Syndrome: Goldenhar Syndrome, AKA Oculo-Auriculo-Vertebral (OAV) syndrome

Etiology: congenital defect characterized by incomplete development of the ear, nose, soft palate, lip, and mandible, usually unilateral. Often synonymous with hemifacial microsomia. It is associated with anomalous development of the first and second branchial arches

Diagnosis: No genetic test available. Diagnosis made by physician after evaluation of characteristic symptoms.

Systemic/Medical Conditions: Some patients will have growing problems with various organs, especially heart, kidney, lungs. Usually, the organ will either not be present on one side or will be underdeveloped. Also, possible scoliosis, hearing loss, limbal dermoids (benign congenital tumor of the eye, where cornea meets sclera), strabismus is common, abnormal ear formation, tissue tags near the ear.

Oral Manifestations:
hypoplastic mandible/maxilla, possible cleft lip/palate, facial asymmetry, high vaulted palate, class III malocclusions, anterior open bite.

Dental needs/considerations: possible distraction osteogenesis with bone grafting necessary


Syndrome: Achondroplasia

Etiology: Sporadic mutation in 85% of cases (2 parents without achondroplasia may give birth to child with it), or autosomal dominant pattern of inheritance. It is an abnormality of cartilage formation brought on by a change in the DNA for fibroblast growth factor receptor 3. It’s the most common type of dwarfism. If a homozygous child receives copies of gene from both parents, very unlikely the child will survive more than a few months.

Diagnosis: Prenatal ultrasound may show excessive amniotic fluid surrounding the unborn infant. After birth, the infant shows increased front to back head size, along with possible signs of hydrocephalus. X-rays of the long bones can reveal the condition in the newborn.

Signs/Symptoms: Characteristic space between the long and ring fingers (“trident hands”), bowed legs, decreased muscle tone, relatively large head size, prominent forehead, short upper arm and thigh, short stature, spinal stenosis

Oral Manifestations:
Craniofacial: Macrocephaly, prominent forehead (bossing), depressed nasal bridge, maxillary hypoplasia, lip incompetence, foramen magnum stenosis. These may lead to hydrocephalus, apnea, upper-airway obstruction, otitis media, sinusitis, and dental malocclusion.

Dental: Anterior open bite, Class III malocclusions (due to maxillary hypoplasia), possible delayed dental development

Dental needs/considerations: Early Ortho evaluation/intervception for Cl. III malocclusion, place a cushion behind child’s back to reduce back pain (spinal stenosis).

Fanconi Anemia

Fanconi anemia (FA) is a rare inherited anemia (autosomal and X chromosomal recessive DNA instability syndrome)  that over time leads to bone marrow failure, or aplastic anemia. 
Etiology:  It occurs when both parents carry a mutation, or defect, in one of several FA genes, and their child inherits the defective gene from both parents.  Approximately 10 to 20 children are born with FA each year in the US. 
FA is characterized by progressive bone marrow failure, multiple congenital abnormalities, and a predisposition to cancer. There are twelve complementation groups that have been identified, (A B C D1 D2 E F G I L and M) -- FA-A is the most common-- 65% of all individuals have FA-A.    Patients with FA typically have a characteristic appearance.  
Signs/Symptoms of FA  (these can raise a red flag about FA during the first year of life):
  • Skin discolorations (cafe au lait, hypo pigmented spots and hyperpgimented spots)
  • Short stature, abnormal thumbs--- other hand, and skeletal abnormalities
  • Various Congenital Abnormalities
  • Kidney problems
  • Small head or eyes,  irregular ear characteristicsLow birth weight
  • Gastrointestinal problems (bowel issues)
  • Small reproductive organs in males
  • Heart Defects
Since these physical characteristics can be indicative of other conditions, and since some patients may have no obvious physical traits of FA, the condition may not be diagnosed at birth. In fact, children with FA are most often diagnosed between the ages of 6 and 8 when they may exhibit symptoms such as:  Unexplained fatigue, Recurrent colds or viral infections, Recurrent nosebleeds, Easy bruising, Blood in the stool or urine, Shortness of breath, Poor growth / short stature
Dental Characteristics:   
  • Generalized microdontia, supernumerary teeth, congenitally missing teeth, transposition, periodontitis, and gingivitis
  • Squamous cell carcinoma could arise in these patients--risk of SSC is increased in mucosal cavities from oral cavity to anus
  • Oral-dental injuries are a major risk of infection
  • Generalized microdontia is often the most common characteristic
  • Regular dental care is important to keep infection rates low and to have early detection of precancerous lesions (SS Carcinoma)

Treatment for FA:
  • Hormones to stimulate red blood cell production
  • Growth factors to stimulate white blood cell production
  • Bone marrow transplantation (BMT) when the condition becomes severe or if patients are not candidates for hormones or growth factors; BMT can be a cure for the blood problems associated with FA
  • Specialized therapies and surgeries can be used to treat symptoms/complications: 
  • Heart Surgery for heart defect correction
  • Surgery (orthopedic)  to correct anomalies of the hands, fingers and skeletal system
  • Therapies for gastrointestinal (GI), kidney or other problems 
  • Hormonal therapy to treat growth deficiency, thyroid conditions and diabetes

Tuesday, April 24, 2012

Marfan Syndrome


Definition: An autosomal dominant disorder of the connective tissue.

Etiology: Defects in a gene called fibrillin-1. Majority of the cases are genetic, however, up to 30% of cases have no family history.

Frequency: About 1 in 5,000.

Clinical Features:
-Long, thin arms and legs
-Hypermobile joints
-Arachnodactyly (spider-like fingers)
-Armspan is much greater than their height
-Chest that sinks in or sticks out
-Heart valve problems
-Vision problems

Oral Manifestations: Long, narrow face, high palatal vault, prominent lower jaw, crowding and malocclusion.

-Vision problems treated when possible
-Treatment of scoliosis in adolescence
-Medication to slow the heart rate may help prevent stress on the aorta, avoiding participating in competitive and contact sports to avoid injuring the heart.
-Surgical correction of heart valves

Dental Considerations: Possible antibiotic prophylaxis.

Sturge-Weber Syndrome

STURGE-WEBER SYNDROME (Encephalotrigeminal Angiomatosis)

Definition: A rare congenital neurological and skin disorder.

Etiology: Error in mesodermal and ectodermal development. NOT hereditary.

Frequency: Rare.

Clinical Features:
-Port wine stain: vascular malformation that extends into oral cavity
-Angiomas of leptomeninges: benign vascular tumor of leptomeninges (arachnoid and pia mater in CNS)
-Seizure disorders
-Mental retardation

Oral Manifestations: Vascular malformations on buccal mucosa, lips. Lesions can resemble a vascular hyperplasia or large tumor-like mass

Treatment: Depends on the location and severity of the lesions, laser therapy may lighten or remove stains. Anticonvulsants may be indicated.

Amelogenesis Imperfecta

by:  Fotini M. Dionisopoulos 

Etiology:  Amelogenesis Imperfecta (AI) may be inherited by x-linked, autosomal dominant or recessive or sporadic inheritance.  (Multiple inheritance patterns)
   AI interferes with normal enamel formation.  There is usually not an associated systemic disorder.

Occurrence:  The frequency of occurrence has been variably reported from 1:4,000 to 1:14,000

Manifestation:  The most common types of AI include four types:  hypocalficifed, hypoplastic pitted, hypoplastic generalized and hypomaturation.  Under these four major types are fourteen subgroups. The variability of appearance of different types of AI makes identification challenging.

AI Type I (Hypoplastic) is reviewed in the AAPD handbook.  With this type there is an insufficient quantity of enamel, with both dentitions affected.   It is said that anterior open both occurs in 60% of these patients.  Within the subgroups there are different genetic patterns:  the ones that are Autosomal Dominant are:  pitted, localize, smooted, and rough.  The ones that are Autosomal Recessive are:  localized (again), and enamel agenesis.  The only one that has the potential to be x-linked is smooth.

Dental Characteristics:

  • Often times children with AI will have accelerated tooth eruption or will have late eruption
  • Associated pathologies are enlarged follicles, impacted permanent teeth and ectopic eruption
  • Agenesis of second molars has been observed
  • More uncommonly, enamel resorption and ankylosis have been reported
  • Anterior open bite is common in 50% of those with hypoplastic AI, 31% in hypomaturation AI, and 60% in hypocalcified AI

Differential Diagnoses:

  • It is important to differentiate AI from different forms of enamel mineralization issues-- other forms will have a pattern based upon the time of insult thus affecting the enamel forming at the time
  • AI will affected all teeth similarly and have a familial history.
  • AI vs. Fluorosis:  with fluorosis, not all teeth are affected uniformly, often the premolars and second permanent molars are spared.  Also review history of fluoride intake to confirm the diagnosis
  • AI is distinguished from other enamel defects:  confinement to distinct patterns of inheritance, occurrence apart from syndromic, metabolic, or systemic conditions

Kleinfelter’s syndrome

Kleinfelter’s syndrome or XXY syndrome is a condition where males have an extra X chromosome
Etiology:  Nondisjunction occurs with when homologous chromosomes fail to separate producing a sperm with both X and Y chromosomes. 
Frequency: 1:500-1:1000
Clinical features:
-Learning disabilities are common
-Generalized physical limitations and delays in physical milestones
- Tall height
- Abnormal body proportions
- Abnormally large breasts
- Less than normal amount of facial and pubic hair
-More likely to have conditions which affect women: autoimmune disorders, breast cancer, vein diseases and osteoporosis  
- Confirmed with genetic testing. Many boys will be unaware of the condition but symptoms become more dramatic during puberty
- Testosterone therapy may aid in producing a more masculine appearance.
-Psychological counseling to help deal with altered physical appearance and avoid self esteem and deptression issues.

Turner's Syndrome

Turner's Syndrome
Condition in which only a single X chromosome is present.  All persons with this condition are female.
Etiology: Exact cause is not known.  All that is known is that during conception most or all of one the X chromosomes is not transferred to the fetus
Frequency: 1:2000-1:5000
Diagnosis: Genetic testing can be done before birth via amniocentesis or shortly after birth when physical symptoms are present
Clinical features:
-Cardiovascular malformations including heart valves, venous malformations, narrowing of the aorta, or rupture of the aorta
-Amenorrhea and infertility
-Altered skeletal structure most likely due to hormonal abnormalities-prone to osteoporosis and fractures
-thyroid problems
-learning disorders
Oral features:
- micrognathia: small lower jaw
- high-arched palate
-Hormone replacement therapy
-Modern IVF procedures have been successful and patients with turner’s syndrome have successfully given birth to children

Wednesday, April 18, 2012

Vitamin D-Resistant Rickets

by: Fotini M. Dionisopoulos

Vitamin D Resistant Rickets' Vitamin D-resistant rickets is considered a metabolic disorder whose symptoms originate from the age of one with limb deformities and decreased growth. Males are more often affected than females. Vitamin-D Resistant Ricketts can be differentiated from other forms of rickets by family history (is X-linked), normal serum calcium, and marked hypophosphatemia.

Main characteristics: short stature, hypophosphatemia, and Rickets. Bones can be painful, soft, and pliable. Patients have bow legs and skeletal abnormalities.

Etiology: The cause of Vitamin-D Resistant Rickets is related to a selective abnormality in renal phosphate transport resulting in hyperphosphaturia and hypophosphatemia. In hypophosphatemic Vitamin D-resistant rickets (renal rickets) the renal tubules can't resorb phosphorous/control he amount of phosphate excreted in the urine. Hypophosphatemic rickets is caused by low levels of phosphate.

Dental Manifestations: Dentin Abnormalities, * Delayed Primary exfoliation/Delayed Eruption of Permanent Teeth, * Premature Exfoliation of Teeth,. Enamel Defects are not associated with Vitamin D-Resistant Rickets. Also associated with the condition: hypomineralized dentin, increased width to predentin, odontoblastic disorganization (odontodysplasia), decreased alkaline phosphatase activity in tooth germ, and enlarged pulp and pulp horns. Very importantly, there have been "Spontaneous" dental abscesses resulting in pulp infection through abnormally mineralized (interglobular) dentin (Seow, Kim BDS, AAPD Journal, 1991) have also been noted clinically. These teeth did not have a history of caries.

Treatment: is generally through nutritional supplements of phosphate and calcitriol (the activated form of vitamin D)

Dental Treatment: Early dental treatment/prevention is necessary to prevent spontaneous pulp death in primary and permanent teeth.(As a side note for the boards: it is probably good to keep in mind that Vitamin D-resistant rickets, hyperparathyroidism, and pseudo-hyperparathyroidism are all conditions demonstrating characteristic dentinal abnormalities.)