Beare-Stevenson cutis gyrata syndrome

Definition

Beare-Stevenson Cutis gyrata syndrome is a serious, extremely rare inherited disorder affecting the skin, skull, genitals, navel, and anus. This condition often results in early death.

Description

Beare-Stevenson cutis gyrata syndrome is also known as Beare-Stevenson syndrome and cutis gyrata syndrome of Beare and Stevenson. This very rare inherited disease causes serious physical problems affecting many body parts. Cutis gyrata is characterized by an unusual ridging pattern in the skin resembling corrugation in cardboard. This skin corrugation is present from birth and commonly occurs on the head and arms.

All people with Beare-Stevenson cutis gyrata syndrome are mentally retarded or developmentally delayed. The brain, skull, face, respiratory system, and genitals are often malformed. Death at an early age is common.

Genetic profile

Beare-Stevenson cutis gyrata syndrome is an autosomal dominant disorder, meaning that a person needs a change, or mutation, in only one of two copies of the gene involved to manifest the disorder. As of 2001, all reported cases have been sporadic, or random, occurrences, happening in families with no family history of the disease. This syndrome is associated with mutations in FGFR2, a fibroblast growth factor receptor gene. The fibroblast growth factor receptor genes serve as blueprints for proteins important to inhibition of cell growth during and after embryonic development. FGFR2 is located on human chromosome 10 in an area designated as 10q26.

Demographics

As of 2001, less than 10 cases of Beare-Stevenson cutis gyrata syndrome have been reported. Both males and females are affected. The few cases documented in the medical literature suggest that some cases of this disease might be associated with advanced paternal age, or older fathers.

Signs and symptoms

All people with Beare-Stevenson cutis gyrata syndrome are developmentally delayed or mentally retarded. There may be excess fluid on the brain (hydrocephalus ), and the nerve connection between the two halves of the brain (the corpus callosum) may be absent or underdeveloped.

A cloverleaf-shaped skull is a very unusual birth abnormality that is common in infants with Beare-Stevenson cutis gyrata syndrome. Abnormalities in skull shape happen when the sutures (open seams between the bony plates that form the skull) fuse before they typically would. Premature closure of the skull sutures is known as craniosynostosis . Growth of the brain pushes outward on skull plates that have not yet fused, causing characteristic bulges in those areas.

The characteristic face of someone with Beare-Stevenson cutis gyrata syndrome has prominent, bulging eyes that slant downward with droopy eyelids. The middle third of the face is underdeveloped and may appear somewhat flattened. The ears are positioned lower and rotated backward from where they would typically be. Skin ridges may be found in front of the ear. Infants with this condition may be born with teeth.

The most recognizable physical symptom of this syndrome is the unusual ridging, or corrugation, of the skin. This cutis gyrata affects the skin on the scalp, face, ears, lips, and limbs and is usually evident at birth. Patches of skin on the armpits, neck, and groin may also display acanthosis nigricans, unusually dark, thickened patches of skin with multiple delicate growths. Skin tags may be present on the surface of the skin and on the tissues lining the mouth. Affected children usually have a prominent navel and may have extra nipples.

People with this disorder may not be able to fully straighten their arms at the elbow. The skin of the palms of the hands and the soles of the feet often show deep ridging. Affected individuals may have small, underdeveloped fingernails.

Children with Beare-Stevenson cutis gyrata syndrome may have breathing problems and narrowing of the roof of the mouth (cleft palate). The anus may be positioned more forward than normal. The genitals are often malformed and surrounded by corrugated skin. An abnormal stomach valve may cause feeding problems.

Diagnosis

Diagnosis of Beare-Stevenson cutis gyrata syndrome is based on visible hallmark characteristics of the disease. As of 2001, all reported cases have shown hallmark characteristics from birth. DNA testing is available for Beare-Stevenson cutis gyrata syndrome. This testing is performed on a blood sample to confirm a diagnosis made on physical features. Prenatal genetic testing is also available. Beare-Stevenson cutis gyrata may be suspected in an unborn fetus if a hallmark characteristic, like a cloverleaf skull, is visible on prenatal ultrasound.

Treatment and management

There is no cure for Beare-Stevenson cutis gyrata syndrome. Of less than 10 reported cases in the literature, many died early in life. So few people have been diagnosed with this disease that there is no published information regarding its treatment and management.

Prognosis

Early death is common in people with Beare-Stevenson cutis gyrata syndrome, especially among those with a cloverleaf skull.

Resources

PERIODICALS

Hall, B. D., et al. "Beare-Stevenson Cutis Gyrata Syndrome." American Journal of Medical Genetics 44 (1992): 82-89.

Krepelova, Anna, et al. "FGFR2 Gene Mutation (Tyr375Cys) in a New Case of Beare-Stevenson Syndrome." American Journal of Medical Genetics 76 (1998): 362-64.

ORGANIZATIONS

Children's Craniofacial Association. PO Box 280297, Dallas, TX 75243-4522. (972) 994-9902 or (800) 535-3643. contactcca@ccakids.com. <http://www.ccakids.com>.

FACES. The National Craniofacial Assocation. PO Box 11082, Chattanooga, TN 37401. (423) 266-1632 or (800) 332-2373. faces@faces-cranio.org. <http://www.faces-cranio.org/>.

WEBSITES

"Cutis Gyrata Syndrome of Beare and Stevenson." OMIM—Online Mendelian Inheritance in Man.<http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=123790>.

Judy C. Hawkins, MS