Trico-dento-osseous Syndrome

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. Research suggests that Amelogenesis imperfecta of the hypomaturation-hypoplasia type with taurodontism and TDO are two genetically distinct conditions.

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

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. 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. Without it, abnormally high levels of uric acid build up in the body.

Frequency: about 1 in 380,000 people.

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: Treatment for LNS is symptomatic. 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.

Treacher Collins Syndrome

Treacher-Collins syndrome is a genetic condition characterized by a defective protein called treacle, which affects the development of bones and other tissues in the face. The signs and symptoms of this disorder vary greatly, ranging from almost unnoticeable to severe. Over 50% of cases are thought to be caused by a new genetic mutation as there is no family history.

Symptoms:
· Outer part of the ears are abnormal or almost completely missing
· Hearing loss
· Very small jaw (micrognathia)
· Very large mouth
· Defect in the lower eyelid (coloboma)
· Scalp hair that reaches to the cheeks
· Cleft palate

Signs and tests: The child usually will show normal intelligence. Genetic tests can be done to look for mutations in the TCS1 gene. Examination of the infant may reveal a variety of problems, including:
· Abnormal eye shape
· Flat cheekbones
· Clefts in the face
· Small jaw
· Low-set ears
· Abnormally formed ears
· Abnormal ear canal
· Hearing loss

· Defects in the eye (coloboma that extends into the lower lid)
· Decreased eyelashes on the lower eyelid

Treatment: Treatment involves testing for and treating any hearing loss so that a child can perform at a normal level in school. Plastic surgery can treat the receding chin and other defects.

Prognosis: Children with this syndrome typically grow to become normally functioning adults of normal intelligence. Careful attention to any hearing problems helps ensure better performance in school.Complications: Feeding difficulty, speaking difficulty, communication problems, vision problems.

Sturge-Weber Syndrome

Definition: Sturge-Weber Syndrome (encephelotrigeminal angiomatosis) is a congenital, non-familial hamartomatous vescular proliferation mainly involving areas along the trigeminal nerve distribution.

Etiology: Not clear, but is thought to be caused by the presence of a vascular plexus around the portion of the neural tube destined to become the facial skin.

Frequency: Rare.

Clinical Features: Hemangiomas of the skin, face, and oral mucosa, calcifications of the brain, ocular disorders such as glaucoma, epilepsy and mild mental retardation. Facial hemangiomas are the most constant and characteristic finding of this syndrome appear as a bright red or purple and are usually unilateral.

Oral Manifestations: Oral hemangiomas also tend to be unilateral, may involve the maxillary gingival, buccal mucosa, tongue and lips, are usually flat, but may have a raised irregular surface that causes tissue enlargement. Delayed or early and ectopic dental eruptions are also common.

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

Dental Considerations: Symptomatic.

Neurofibromatosis

The neurofibromatoses are genetic disorders that cause tumors to grow in the nervous system. The tumors begin in the supporting cells that make up the nerves and the myelin sheath. These disorders cause tumors to grow on nerves and produce other abnormalities such as skin changes and bone deformities. Although many affected persons inherit the disorder, between 30 and 50 percent of new cases arise spontaneously through mutation in an individual's genes. Once this change has taken place, the mutant gene can be passed on to succeeding generations.

Neurofibromatosis type 1 (NF1) is the most common type of the neurofibromatoses. Changes in skin appearance, tumors, or bone abnormalities occur. Symptoms of NF1, which may be evident at birth and nearly always by the time the child is 10 years old, may include light brown spots on the skin "cafe-au-lait" spots), two or more growths on the iris of the eye, a tumor on the optic nerve, a larger than normal head circumference, and abnormal development of the spine, a skull bone, or the tibia.
Treatment: Surgery is often recommended to remove the tumors. Some NF1 tumors may become cancerous, and treatment may include surgery, radiation, or chemotherapy.
Prognosis: In most cases, symptoms of NF1 are mild, and individuals live normal and productive lives. In some cases, however, NF1 can be severely debilitating and may cause cosmetic and psychological issues.

NF2 is less common and is characterized by slow-growing tumors on the eighth cranial nerves. The tumors cause pressure damage to neighboring nerves. Tumors in the 8th nerve, cataracts at an early age or changes in the retina that may affect vision, other nervous system tumors are manifestations. It often starts in the teen years.
Treatment: MRIs can reveal tumors as small as a few millimeters in diameter, thus allowing early treatment. Surgery to remove tumors completely is one option but may result in hearing loss.
Prognosis: The course of NF2 varies greatly among individuals. In some cases of NF2, the damage to nearby vital structures, such as other cranial nerves and the brain stem, can be life-threatening.

Schwannomatosis is the rarest of the three types and is characterized by the development of multiple schwannomas everywhere in the body except on the vestibular branch of the 8th cranial nerve. The dominant symptom is pain, which develops as a schwannoma enlarges or compresses nerves or adjacent tissue. Some people may develop numbness, tingling, or weakness in the fingers and toes.
Treatment: There is no currently accepted medical treatment or drug for schwanomatosis, but surgical management is often effective. Pain usually subsides when tumors are removed completely.
Prognosis: Most individuals with schwannomatosis have significant pain. In some extreme cases the pain will be severe and disabling.

Oral lesions occur in 60-70% of cases and are characterized by multiple or isolated nodular neurofibromas, which vary in size. Tumors usually involve the tongue although other areas of mucosa may be affected. Enlargement of the fungiform papilla is common. Macroglossia is less common and lesions of the maxilla and mandible are relatively uncommon.

Marfan Syndrome

Definition: An autosomal dominant disorder of the connective tissue. MFS features can occur in many different parts of the body.

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, scoliosis and arachnodactyly. Arm span is much greater than their height. A chest that sinks in or sticks out -- funnel chest or pigeon breast. Flat feet, hypotonia, hyperflexible joints, learning disabilities, severe myopia or dislocation of the lens of the eye, aortic dilation or aortic aneurysm, heart valve problems, or collapsed lung.

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

Treatment: Vision problems should be 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. Some people may need surgical replacement of the aortic root and valve.

Dental Considerations: Antibiotic prophylaxis and orthodontic care.
Prognosis: Heart-related complications may shorten the lifespan of people with this disease. However, many patients survive well into their 60s. Good care and surgery may extend the lifespan further.

Beckwith-Wiedemann Syndrome

Syndrome: Beckwith Wiedemann Syndrome
Etiology: Congenital overgrowth disorder that is caused by a sporadic genetic mutation in 85% of cases. Genetics are complex, but chromosome 11 has been implicated as the problem area. BWS remains a clinical diagnosis because physicians cannot identify and test for all the genetic causes of BWS.
Five common features used to define BWS are: macroglossia (large tongue), macrosomia (birth weight and length >90th percentile), midline abdominal wall defects (omphalocele-intestines, liver, other organs remain outside the abdomen in a sac b/c of defect in abdominal wall muscles, umbilical hernia, diastasis recti-separation of rectus abdominis muscles into right/left halves), ear creases or ear pits, and neonatal hypoglycemia (low blood sugar after birth).
Diagnosis: Patients normally don’t present with all 5 features. Child is considered to have the syndrome if it has been diagnosed by a physician and they present with at least 2 of the 5 major features.
Systemic/Medical Conditions: Patients have higher risk of developing cancer, although 80% do not. Most common tumors are Wilms’ tumor (nephroblastoma) and hepatoblastoma. Both can usually be cured if diagnosed early.
Oral Manifestations: Macroglossia (one of the five principal features)
Dental needs/considerations: Macroglossia in BWS becomes less noticeable with age and often requires no treatment; but it does cause problems for some patients. In severe cases, macroglossia can cause respiratory, feeding, and speech difficulties. Children with BWS and significant macroglossia should be evaluated by a craniofacial team. Early orthodontic intervention can halt problems before they progress (open bite, mouth breathing, protrusion of teeth)
The best time to perform surgery for a large tongue is not known. Some surgeons recommend performing the surgery between 3 and 6 months of age. Surgery for macroglossia involves removing a small part of the tongue so that it fits within the mouth to allow for proper jaw and tooth development.

de Lange Syndrome

Syndrome: De Lange Syndrome (Cornelia de Lange Syndrome)
Etiology: Genetic disorder that can lead to serious developmental anomalies, affecting both physical and intellectual development of a child. Most due to spontaneous mutations. No specific gene associated.
Diagnosis: solely a clinical diagnosis right now. There are no biochemical or chromosomal markers for DLS yet.
Systemic/Medical Conditions:
• Low birth weight (usually under 5 pounds / 2.5 kilograms)
• Delayed growth and small stature
• Developmental delay
• Limb differences (missing limbs or portions of limbs)
• Small head size (microcephaly)
• Thick eyebrows, which typically meet at midline (synophrys)
• Long eyelashes
• Short upturned nose and thin downturned lips
• Long philtrum
• Excessive body hair
• Small hands and feet
• Small widely spaced teeth
• Low-set ears
• Hearing impairments
• Vision abnormalities (e.g., ptosis, nystagmus, high myopia, hypertropia)
• Partial joining of the second and third toes
• Incurved 5th fingers
• Gastroesophageal reflux
• Seizures
• Heart defects
• Cleft palate
• Feeding problems
Children with this syndrome are often found to have long eyelashes, bushy eyebrows and synophrys- Unibrow!
Children with CdLS often suffer from gastrointestinal tract difficulties, particularly gastroesophageal reflux. Vomiting, intermittent poor appetite, constipation, diarrhea or gaseous distention are known to be a regularity in cases where the GE tract problems are acute. However, symptoms may range from mild to severe.
Oral Manifestations: Some dental abnormalities reported include delayed eruption, spacing and macro- or microdontia.
Recent Info: 2009 study out of Turkey found possible correlation between CdLS and Hutchinson’s teeth.

Trisomy 9 Mosaicism

Definition: 9th chromosome appears three times (trisomy) rather than twice in some cells of the body. The term "mosaic" indicates that some cells contain the extra chromosome 9, while others have the normal chromosomal pair.

Etiology: Errors during meiosis or mitosis

Frequency: Rare

Diagnosis: Take samples from multiple tissues for diagnosis

Clinical features: Associated symptoms and findings may vary greatly in range and severity, depending on the percentage of cells with the extra chromosome.

Growth deficiency before birth, mental retardation, congenital heart defects, craniofacial abnormalities (sloping forehead, bulbous nose, short palpebral fissures, deeply set eyes, and low-set ears, small jaw, large fontanels), musculoskeletal, genital, kidney issues.

Rubenstein-Taybi Syndrome

Other names: Broad thumb-hallux syndrome or Rubinstein syndrome

Definition: Condition characterized by short stature, moderate to severe learning difficulties, distinctive facial features, and broad thumb and first toes.

Etiology: Autosomal Dominant

Frequency: Uncommon 1:125,000

Clinical features: Broad thumbs and broad first toes, mental disability, small height, bone growth, small head, cryptorchidism in males (absence of one or both testes from the scrotum), unusual facial features (flat red birthmark on forehead, widely spaced eyes, downward slant of eyes, strabismus (cross eyed), droopy eyelids, high arched eyebrows, beaked nose, broad nasal bridge, extra fold of skin on either side of nose, malformed ears, high-arched palate, crowded teeth, small lower jaw), hirsutism (excess hair on body), hyperextensible joints, small tilted pelvis, seizures, slow development of cognitive and motor skills along with low muscle function, unsteady gait, feeding difficulties, respiratory infections, eye infections, heart defects, vertebral abnormalities, G.I. reflux, and kidney problems

Increased risk of noncancerous and cancerous tumors, leukemia, and lymphoma

Treatment: Individuals with RTS have a range of mild to severe symptoms. Most children will benefit from speech therapy. Some children may not be able to speak verbally, and therefore, would may need to learn sign language.