Rothmund-Thomson syndrome

Definition

Rothmund-Thomson syndrome (RTS) is an extremely rare inherited disorder that appears in infancy and features skin degeneration (atrophic dermatosis), clouding of the lenses of the eyes (juvenile cataracts), skeletal abnormalities, short stature, and an increased risk of skin and bone cancers.

Description

Rothmund-Thomson syndrome is usually first apparent between three and six months of age. This disorder is characterized by early sun sensitivity and progressive degeneration or wasting (atrophy) of the skin as well as scarring and abnormal pigmentation of the skin. Other characteristic signs include sparse hair, clouding of the lenses of the eyes (juvenile cataracts), short stature, malformations of the face and head, teeth, nails, and bone, and other physical abnormalities. In rare cases, mental retardation may be present.

The syndrome was first described in 1868 by August von Rothmund, a German ophthalmologist, and in both 1923 and 1936 by Matthew S. Thomson, a British dermatologist. Both independently noted a familial disorder with cataracts, saddle nose, and skin degeneration. It is believed that Thomson's finding was the same disease that was seen long before by Rothmund. Other names for Rothmund-Thomson syndrome include poikiloderma congenita and poikiloderma atrophicans with cataract.

Genetic profile

Rothmund-Thomson is attributed to a mutation in a gene located on chromosome 8. Mutations in the gene RecQL4 (chromosomal locus 8q24), also called the Rothmund-Thomson gene, have been identified in four patients with Rothmund-Thomson syndrome.

Rothmund-Thomson syndrome is inherited as an autosomal recessive trait. This means that both parents have one copy of the Rothmund-Thomson gene but do not have the disease. Each of their children has a 25% chance of not having the gene, a 50% chance of having one Rothmund-Thomson gene (and, like the parents, being unaffected), and a 25% risk of having both Rothmund-Thomson genes and the disease.

Demographics

There is no specific population group that is at greater risk for this disorder, although it is more common in women (2:1). Evidence of Rothmund-Thomson syndrome has been found to occur in all races and many nationalities. The majority of affected people are from full-term pregnancies. As of the year 2001, a total of approximately 250 cases have been reported in English-speaking medical literature. The number of carriers for Rothmund-Thomson syndrome is unknown.

Signs and symptoms

The major characteristics of Rothmund-Thomson syndrome are skin abnormalities, short stature, juvenile cataracts, small hands, and delayed activities of the ovaries in females or testes in males. Symptoms vary from individual to individual.

Skin abnormalities usually appear in infancy, between three and six months of age. Skin changes begin as red inflamed patches, occasionally with blistering, on the cheeks along with swelling and then spread to other areas of the face, the arms and legs, and buttocks. Skin inflammation eventually subsides and a condition develops known as poikiloderma, characterized by abnormal widening (dilation) of groups of small blood vessels (telangiectasia), skin tissue degradation (atrophy), and patchy areas of abnormally decreased and/or unusually increased brown pigmentation (depigmentation and hyperpigmentation), giving the skin a mottled look. Skin that is exposed to the sun usually shows greater abnormalities. Sun sensitivity typically continues throughout the affected person's life. Those with extreme sun sensitivity can develop thickening of the skin (keratosis) of the face, hands, and feet, or cancerous skin changes later in life. Affected individuals are at increased risk of developing skin cancers (basal cell carcinoma and squamous cell carcinoma) and bone cancer (osteosarcoma).

There are many other physical abnormalities that affect people with Rothmund-Thomson syndrome. Juvenile cataracts, the clouding of the lenses of the eyes, develop in almost half of the people with RTS between the ages of four and seven. Severe growth delays result in short stature throughout life. Skeletal abnormalities such as unusually small hands and feet are common. Less typical are stubby fingers and toes, underdeveloped (hypoplastic) or absent thumbs, and/or underdeveloped (hypoplastic) or missing forearm bones (ulna and radii). Hypogonadism, the deficient activity of the ovaries in females or testes in males, causes irregular menstruation in females, and delayed sexual development and reduced fertility in both males and females. Facial skeletal abnormalities include a triangular-shaped face with a prominent forehead (frontal bossing), a sunken nasal bridge (saddle nose), and a protruding lower jaw (prognathism). Scalp hair is usually thin and fine, although alopecia (balding) occasionally occurs in early childhood. Often the eyebrows and eyelashes are sparse or absent. Dental abnormalities include excessive cavities, unusually small teeth (microdontia), or delayed or failure of teeth to erupt. Dysplastic, or abnormally developed nails are also seen in many people with Rothmund-Thomson syndrome.

Diagnosis

A diagnosis of Rothmund-Thomson syndrome is made based on clinical examination. There are no laboratory diagnostic tests. Mutations of the RecQL4 gene have been found in a few individuals with RTS. However, as of the year 2001, genetic testing is still on a research basis and is not available for diagnostic purposes.

There are no published diagnostic criteria. Diagnosis is usually based on the presence of the characteristic poikilodermatous rash in childhood, along with one or more of the following features: small stature, sparse or absent hair, cataracts, and cancer.

Treatment and management

Essential management of Rothmund-Thomson syndrome includes avoiding sun exposure and diligently using sunscreen that has both UVA and UVB protection.

An ophthalmologic evaluation for the detection and management of cataracts is recommended for affected people on an annual basis up to age 15. Surgical removal of significant cataracts may be necessary.

Because skin cancer is a risk, it is important to monitor the affected individual closely for lesions with unusual color or texture. They should also be watched carefully for any signs and symptoms of osteosarcoma, a cancerous bone tumor, including bone pain, swelling, or a growing lesion on the arms or legs.

Pulsed-dye laser therapy has been used to treat the widening of small blood vessels (telangiectases). Medications called retinoids can reduce the potential for skin cancer. Keratolytic drugs are used to cause thick skin to swell, soften, and then fall away.

Prognosis

Individuals with Rothmund-Thomson syndrome usually have a normal life span, although an increased risk for bone and skin cancer has been found. Most affected individuals will have normal intelligence, however learning disabilities and mental retardation have been reported in a small number of patients.

Resources

PERIODICALS

Hall, Judith G., et al. "Rothmund-Thomson Syndrome with Severe Dwarfism." American Journal of Diseases of Children 134 (1980): 165–169.

Starr D. G., et al. "Non-Dermatological Complications and Genetic Aspects of the Rothmund-Thomson Syndrome." Clinical Genetics 27 (1985): 102–104.

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

Plon, Sharon E., MD, PhD, and Lisa L. Wang, MD. (October 6, 1999). "Rothmund-Thomson syndrome." GeneClinics. University of Washington, Seattle. <http://www.geneclinics.org/profiles/rts>.

Nina B. Sherak, MS, CHES