Hemihypertrophy (Hemihyperplasia)

Definition

Hemihypertrophy, more correctly termed hemihyperplasia, is defined as the enlargement of one side of the body or part of the body.

Description

Hemihypertrophy is characterized by unequal (asymmetric) growth of the cranium, face, trunk, limbs, and/or digits. Hemihypertrophy can be an isolated finding, or it can be associated with certain malformation syndromes. Isolated hemihypertrophy refers to hemihypertrophy for which no cause can be found. The degree of asymmetry is variable and very mild cases can go undiagnosed. There are three categories of hemihypertrophy, depending on the body parts involved. The size difference can involve only a specific part of the body such as a finger (called simple hemihypertrophy) or an entire half of the body (called total or complex hemihypertrophy). It usually involves only one side of the body, but can involve both sides (called crossed). There is also hemifacial hyperplasia, which involves one side of the face. Usually multiple organ systems are involved, i.e. the skin, vascular system, internal organs, or bones. In complex hemihypertrophy, the right side is more often involved than the left.

Hemihypertrophy may involve not only the part of the body that is visible, but also the underlying internal organs. Enlargement of one kidney, adrenal gland, testis, and ovary has been reported. The enlarged area usually also has thickened skin, more sebaceous (sweat) glands, more hair, may have pigmentary abnormalities, and the bones may be larger or may be deformed. In persons with facial involvement, the asymmetry can include cheek, lip, nose, ear, eye, tongue, jaw, roof of the mouth, or teeth.

The nervous system may also be affected, causing unilateral nerve enlargement or sciatic nerve inflammation. Occasionally a part of the brain is affected causing mental retardation (15% to 20% of cases). Many cases of hemihypertrophy have hamartomatous lesions (birth marks which involve blood vessels) or abnormalities of the genito-urinary system.

As with other overgrowth syndromes, there is an increased risk for childhood cancers in people with isolated hemihypertrophy (about 6%), particularly cancers of the kidney (Wilms tumor, 3% of individuals), adrenals, and liver.

Genetic profile

The cause and exact mechanism of isolated hemihypertrophy is not known. The asymmetry occurs most likely as a result of an increase in the rate of cell growth, or unregulated cell growth. Most cases of hemihypertrophy are not inherited, but there have been seven familial cases reported as of 2000 in which two or more persons were affected. These cases are not well documented and it is possible that the families actually had another genetic syndrome. Males and females are equally affected with this condition.

It is clear that there is not a single gene responsible for hemihypertrophy, but the exact number of genes and their locations and functions are not known. It has been suggested that isolated hemihypertrophy may be related to another condition, called Beckwith-Wiedemann syndrome , a genetic overgrowth syndrome that can include both hemihypertrophy and Wilms tumor. Beckwith-Wiedemann syndrome has been associated with abnormalities on chromosome 11, which contains genes involved with growth, development, and cancer .

Good data does not exist for recurrence risk for siblings of patients or for children of affected persons. Case reports suggest a slightly increased risk for siblings and for offspring of affected mothers.

Demographics

Hemihypertrophy occurs in about one in 15,000 live births. Isolated hemihypertrophy occurs in about one in 86,000 live births. There are approximately 200 cases reported. Females and males are affected equally.

Signs and symptoms

Hemihypertrophy is usually recognized at birth by physical examination, but can become more serious over time, especially during puberty. Very mild forms of this condition often go unnoticed and are very common.

Diagnosis

The diagnosis is made by clinical examination of body asymmetry. There are no laboratory tests available for this condition. X ray may show advanced bone age or larger bones in the hypertrophied limbs, supporting a diagnosis of hemihypertrophy, or characteristic bone changes supporting another diagnosis. Other genetic syndromes associated with asymmetry must be excluded, as must other causes of asymmetry, such as atrophy of one side of the body due to neurological disorder or skeletal abnormalities that cause asymmetric hand or limb enlargement.

Prenatal diagnosis is theoretically possible by ultrasound, provided that the difference in size is large enough to be detected or if an embryonic tumor is present, although a confirmed diagnosis is not possible until after birth.

Treatment and management

The treatment for hemihypertrophy is different for each individual and depends on the specific symptoms. If leg-length differences are present, corrective shoes can increase the sole for the unaffected leg to prevent scoliosis and walking difficulties. Orthopedic devices such as braces or, more rarely, surgery to lengthen the normal leg may be indicated. Surgery to retard growth of the over-grown leg is controversial and not recommended. Surgery for congenital defects or laser surgery for birth marks may be indicated. Plastic surgery may be considered to correct very discrepant facial features.

A protocol to screen for childhood cancers has been proposed, which includes abdominal ultrasound every three months until age six, every six months until puberty, and careful medical follow-up of patients into adulthood. Surgical intervention is appropriate if cancers are detected. Monitoring of serum alpha fetoprotein levels may also be useful as a marker of hepatic tumors.

Appropriate special education services are necessary for those with mental retardation. Counseling related to social stigmatism may be necessary if severe disfigurement is an issue.

Prognosis

Hemihypertrophy does not alter lifespan, although complications from associated abnormalities such as childhood cancer and mental retardation can cause problems. Asymmetry of the limbs can interfere with their proper function and cause pain. Insecurities due to disfigurement are possible and can be addressed through support groups or therapy.

Resources

BOOKS

Buyse, M.L., ed. "Hemihypertrophy." In Birth Defects Encyclopedia. Boston: Blackwell Scientific Publications, 1990.

Goodman, R.M., and R.J. Gorlin. "Hemihypertrophy." In The Malformed Infant and Child. New York: Oxford University Press, 1983.

PERIODICALS

Biesecker, L.G., et al. "Clinical Differentiation Between Proteus Syndrome and Hemihyperplasia: Description of a Distinct Form of Hemihyperplasia." American Journal of Medical Genetics 79 (1998): 311-318.

Hoyme, H.E., et al. "Isolated Hemihyperplasia (Hemihypertrophy): Report of a Prospective Multicenter of the Incidence of Neoplasia and Review." American Journal of Medical Genetics 79 (1998): 274-278.

ORGANIZATIONS

Klippel-Trenaunay Support Group. 5404 Dundee Rd., Edina, MN 55436. (612) 925-2596.

Proteus Syndrome Foundation. 6235 Whetstone Dr., Colorado Springs, CO 80918. (719) 264-8445. [email protected]. <http://www.kumc.edu/gec/support/proteus.html>.

WEBSITES

"Hemihypertrophy." Online Mendelian Inheritance in Man.<http://www.ncbi.nlm.nig.gov/entrez/dispomim.cgi?id=235000>.

National Organization of Rare Disorders. <http://www.rarediseases.org>.

Amy Vance, MS, CGC