Adams-Oliver Syndrome

views updated

Adams-Oliver syndrome

Definition

Adams-Oliver syndrome (AOS) is a condition involving the combination of congenital scalp defects (called aplasia cutis congenita) and a specific type of limb defect.

Description

Adams-Oliver syndrome is a genetic condition characterized by aplasia cutis congenita, most commonly of the scalp and skull, and terminal transverse limb defects. Congenital heart disease has also been reported in individuals with this condition. The exact cause of the condition is not well-understood. There is extreme variability in the severity of problems between families with AOS.

Genetic profile

There have been both familial and non-familial cases of Adams-Oliver syndrome reported. The majority of genetic cases have been inherited in an autosomal dominant manner, but since autosomal recessive and sporadic inheritance have also been reported. A difference in the presentation of AOS in the dominant versus recessive form has not been documented.

Autosomal dominant inheritance means that only one abnormal gene copy is required for the disease to occur. For persons with a copy of the gene, the risk of passing it to their offspring is one in two or 50%.

Autosomal recessive inheritance means that two defective gene copies must be inherited, one from each parent, for the disease to manifest itself. Persons with only one gene mutation are carriers for the disorder. Individuals who are carriers for the recessive type of Adams-Oliver syndrome do not have any symptoms (asymptomatic) and do not know they are carriers unless they have had a child with the syndrome. Carrier testing is not available since the gene location is not known at this time. The likelihood that each member of a couple would be a carrier for a mutation in the same gene is higher in people who are related (called consanguineous). When both parents are carriers for the recessive type of Adams-Oliver syndrome, there is a one in four chance (25%) in each pregnancy for a child to have the disease. There is a two in three chance that a healthy sibling of an affected child is a carrier.

Sporadic occurrences of AOS may be caused by a dominant gene with variable expressivity (no one else in the family has symptoms, but some are actually gene carriers), a new (dominant) mutation occurring during the formation of the embryo where neither parent is a carrier, or the existence of both genetic and non-genetic causes for the same syndrome.

Different mechanisms have been postulated to explain how Adams-Oliver syndrome occurs. They include trauma, uterine compression, amniotic band sequence (a condition resulting from strands of the amnion membrane causing amputation of parts of the fetus), vascular disruption (blockage of blood flow to a developing part or parts of the fetus), and a large blood clot in the placenta which blocks certain important blood vessels and interrupts blood supply to developing structures. Recently, Adams-Oliver syndrome has been hypothesized to occur as a result of abnormalities in small vessel structures that occur very early in embryo formation. The vascular anomaly could be the result of a genetic defect causing decreased stability of embryonic blood vessels in the presence of specific forces.

Demographics

Adams-Oliver syndrome was first described in 1945. There have been over 125 cases reported in the medical literature. There does not appear to be any ethnic difference in prevalence of this condition.

Signs and symptoms

Limb defects are the most common occurrence in Adams-Oliver syndrome, affecting about 84% of patients. The type of limb defect is usually asymmetrical (not the same on both sides), with a tendency to involve both sides of the body (bilateral), more often the lower limbs than the upper limbs. There is a wide range of severity in the limb defects, from something minimal like small or missing finger or toenails (called nail hypoplasia), to the more severe absence of hands, feet, or lower legs. Other more moderate limb defects that have been reported include webbing (syndactyly) of the skin (cutaneous syndactyly) or bones (bony syndactyly) of the fingers or toes, claw-hand malformation (ectrodactly), and brachydactyly (shortened fingers or toes). Brachydactyly is the most common limb defect in AOS.

Congenital cutis aplasia is the second most common problem and is present in about 75% of patients with Adams-Oliver syndrome. In 64% of patients with congenital cutis aplasia, there is also an underlying scull defect. More rarely, scull defects can be seen without scalp defects and may be mistaken for an enlarged soft spot (fontanelle).

Congenital heart defects have been reported to occur in between 13%-20% of patients with Adams-Oliver syndrome.

Many different types of vascular (involving the blood vessels) and valvular (with heart valves) problems have been reported in these patients.

Other clinical features seen with AOS, include short stature, kidney (renal) malformations, cleft palate, small eyes (micropthalmia), spina bifida occulta, extra (accessory) nipples, undescended testes, skin lesions, and neurological abnormalities. Mental retardation is present in a few cases.

Diagnosis

Aplasia cutis congenita is a physical finding that has many causes. To determine whether a patient has Adams-Oliver syndrome clinically, all individuals with aplasia cutis congenita should have a complete pregnancy and family history taken, as well as a complete medical evaluation. When possible, relevant family members should be examined for evidence of the condition. When aplasia cutis congenita is discovered at birth, the placenta should be evaluated. Physical exam of the affected infant includes evaluation of other related structures, specifically teeth, hair, and other areas of skin, nails, and central nervous system. Once this evaluation has been completed and a specific diagnosis of Adams-Oliver syndrome has been established or refuted, genetic counseling can be provided.

Prenatal diagnosis by ultrasound of the limb defects and possibly some other abnormalities associated with AOS is possible, but clinical confirmation of the diagnosis occurs after birth. Since the gene (or genes) causing AOS have not been isolated, prenatal diagnostic procedures such as amniocentesis or chorionic villus sampling are not indicated.

Treatment and management

The treatment for AOS is different for each individual and is tailored to the specific symptoms. If leg-length discrepancy is present, corrective shoes that increase the sole for the unaffected leg to prevent scoliosis and ambulation difficulties can be worn. Orthopedic devices such as prostheses are sometimes recommended. Patients should be referred to a physician specializing in treating patients with limb defects early in life. Surgery for congenital defects and skin grafting for scalp defects may be necessary (about 30% of patients required skin grafting in one study).

Special devices for writing or other activities may be necessary if hand malformations are present.

About 30% of patients in one study suffered major hemmorrhage from the scalp defect. Twenty percent of patients had local infection of the scalp defect. Treatment such as transfusion or antibiotic therapy may be required in these cases.

Appropriate special education services are necessary for those with mental retardation. Counseling and support related to limb defeciency issues are essential for coping. Support groups can provide valuable peer referrals and information.

Prognosis

AOS does not usually alter life span, although complications from associated abnormalities such as mental retardation can cause problems. About 5% of the scalp defects that hemorrhaged severely were fatal. Rare cases of meningitis as a result of infection of the scalp defect have been reported. Asymmetry of the limbs can interfere with their proper function and cause pain. Psychological issues relating to disfigurement are possible.

Resources

BOOKS

Sybert, V. P. "Aplasia cutis congenita: A report of 12 new families and review of the literature." Pediatric Dermatology, volume 3. Blackwell Scientific Publications, 1985, pps 1-14.

PERIODICALS

Amor, D., R. J. Leventer, S. Hayllar, and A. Bankier. "Polymicrogyria associated with scalp and limb defects: Variant of Adams-Oliver syndrome." American Journal of Medical Genetics 93 (2000): 328.

Swartz, E. N., S. Sanatani, G. S. Sandor, and R. A. Schreiber. "Vascular abnormalities in Adams-Oliver syndrome: Cause or effect?" American Journal of Medical Genetics 82 (1999): 49.