Multiple lentigenes syndrome is a rare genetic condition that causes the affected individual to have many dark brown or black freckle-like spots on the skin, as well as other symptoms.
Description
Multiple lentigenes syndrome is a genetic disorder that results in characteristic marking of the skin, abnormalities in the structure and function of the heart, hearing loss, wide-set eyes, and other symptoms. Other terms for multiple lentigenes syndrome include cardiomyopathic lentiginosis and LEOPARD syndrome. LEOPARD syndrome is an acronym for the seven most commonly observed symptoms of the disorder:
(L)entigenes, or small dark brown and black spots on the skin;
(E)lectrocardiographic conduction defects, or abnormalities of the muscle activity in the heart;
(O)cular hypertelorism, or eyes that are spaced farther apart than normal;
(P)ulmonary stenosis, or narrowing of the lower right ventricle of the heart;
(R)etarded growth leading to shortness of stature;
(D)eafness or hearing loss.
The lentigenes, or skin spots, observed in multiple lentigenes syndrome are similar in size and appearance to freckles, but unlike freckles, they are not affected by sun exposure.
Genetic profile
Multiple lentigenes syndrome is inherited as an autosomal dominant trait. Autosomal means that the syndrome is not carried on a sex chromosome, while dominant means that only one parent has to pass on the gene mutation in order for the child to be affected with the syndrome.
As of 2001, the specific gene mutation responsible for multiple lentigenes syndrome had not been identified.
Demographics
Multiple lentigenes syndrome is extremely rare. Due to the small number of reported cases, demographic trends for the disease have not been established. There does not seem to be any clear ethnic pattern to the disease. Both males and females appear to be affected with the same probability.
Signs and symptoms
The most characteristic symptom of the disease is the presence of many dark brown or black spots, ranging in size from barely visible to 5 cm in diameter, all over the face, neck, and chest. They may also be present on the arms and legs, genitalia, palms of the hands, and soles of the feet. The spots appear in infancy or early childhood and become more numerous until the age of puberty. There may also be lighter brown (café au lait) birthmarks on the skin.
Heart defects, such as the pulmonary stenosis and electrocardiographic conduction abnormalities described above, are another hallmark of multiple lentigenes syndrome. Other areas of narrowing (stenosis) in different areas of the heart may be present, as well as abnormalities in the atrial septum, the wall between the upper left and right chambers of the heart. There is an increased risk of heart disease and tumors of the heart.
In addition to the feature of widely spaced eyes, other facial abnormalities may include low-set or prominent ears, drooping eyelids, a short neck, or a projecting jaw. In some cases of multiple lentigenes syndrome, additional skeletal malformations have been reported, including a sunken breastbone, rib anomalies, curvature of the spine (scoliosis), and webbing of the fingers.
Deafness or hearing loss is observed in about 25% of the cases of multiple lentigenes syndrome. Some people affected with the syndrome also exhibit mild developmental delay. Other reported neurological findings include seizures, eye tics, and abnormal electrical activity in the brain.
People with multiple lentigenes syndrome often exhibit genital abnormalities such as undescended testicles or a small penis in men, or missing or underdeveloped ovaries in women. The onset of puberty may be delayed or even absent. Affected individuals are usually under the twenty-fifth percentile in height, although their body weight is in the normal range.
Diagnosis
Diagnosis is usually made based on the observation of multiple lentigenes and the presence of two or more of the other symptoms that form the LEOPARD acronym. A family history is also helpful since the syndrome has dominant inheritance. There is currently no medical test that can definitively confirm the diagnosis of multiple lentigenes syndrome.
Treatment and management
Treatment is directed toward the specific conditions of the individual. For example, heart conditions can be managed with the use of a pacemaker and appropriate medications, as well as regular medical monitoring. Hearing loss may be improved with the use of hearing aids.
Genetic counseling is recommended when there is a family history of freckle-like spotting of the skin and heart defects, as these suggest the possibility of inherited multiple lentigenes syndrome.
Prognosis
The prognosis for people with multiple lentigenes syndrome is good provided that the appropriate care for any associated medical conditions is available.
PERIODICALS
Abdelmalek, Nagla, and M. Alan Menter. "Marked cutaneous freckling and cardiac changes." Baylor University Medical Center Proceedings (December 1999): 272-274.
ORGANIZATIONS
National Organization for Rare Disorders (NORD). PO Box 8923, New Fairfield, CT 06812-8923. (203) 746-6518 or (800) 999-6673. Fax: (203) 746-6481. <http://www.rarediseases.org>.
WEBSITES
HealthlinkUSA Forum—LEOPARD Syndrome. http://www.healthlinkusa.com/forum/709_1.html (20 April 2001).
