Sjögren-Larsson Syndrome

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Sjögren-Larsson syndrome

Definition

Sjögren-Larsson syndrome is an inherited disorder characterized by ichthyosis (scaly skin), speech abnormalities, mental retardation, and spasticity (a state of increased muscle tone with heightened reflexes). Severity is variable.

Description

Sjögren-Larsson syndrome is a rare genetic disorder inherited in an autosomal recessive fashion. First characterized by Swedish psychiatrist Torsten Sjögren in 1956 Sjögren and Tage Larsson in 1957), they suggested that all Swedes with the syndrome are descended from one ancestor in whom a mutation (a genetic change) occurred about 600 years ago. The highest incidence of the disease occurs in northern Sweden.

In infancy, development of various degrees of scaling and reddened skin occurs, often accompanied by hyperkeratosis (thickening of the skin) on the outer skin layer. After infancy, skin on the arms, legs and abdomen often is dark, scaly, and lacking redness. Seizures and speech abnormalities may accompany skin symptoms. About half of children affected with the syndrome experience degeneration of the pigment in the retina of the eye. (and by Sjögren-Larsson syndrome is also sometimes known as SLS; congenital ichthyosis-mental retardation-spasticity syndrome; ichthyosis-spastic neurologic disorder-oligophrenia syndrome; fatty aldehyde dehydrogenase deficiency (FALDH deficiency); fatty aldehyde dehydrogenase 10 deficiency (FALDH10 deficiency); or disorder of cornification 10 (Sjögren-Larsson Type).

Sjögren-Larsson syndrome is not to be confused with Sjögren syndrome; it is sometimes called the T. Sjögren syndrome to distinguish it from Sjögren syndrome (characterized by dry eyes and mouth), which was described by Swedish ophthalmologist Henrick Sjögren.

Genetic profile

Inheritance of Sjögren-Larsson syndrome is autosomal recessive. In autosomal recessive inheritance, a single abnormal gene on one of the autosomal chromosomes (one of the first 22 "non-sex" chromosomes) from both parents can cause the disease. Both of the parents must be carriers in order for the child to inherit the disease since recessive genes are expressed only when both copies in the pair have the same recessive instruction. Neither of the parents has the disease (since it is recessive).

A child with both parents who carry the disease has a 25% chance having the disease; a 50% chance of being a carrier of the disease (but not affected by the disease, having both one normal gene and one gene with the mutation for the disorder); and a 25% chance of receiving both normal genes, one from each parent, and being genetically normal for that particular trait.

The gene for the Sjögren-Larsson syndrome, FALDH, is located on chromosome number 17 in band 17p11.2. The gene mutation that is responsible for the disorder is located near the center of the chromosome and is strongly associated the gene markers called D17S805 and ALDH10.

Demographics

Sjögren-Larsson syndrome is a rare disorder. The highest incidence occurs in northern Sweden. The mutation responsible for the disease is present in approximately 1% of the population in northern Sweden. All Swedes with the syndrome are believed to be descendents of one ancestor in whom a genetic change occurred about 600 years ago. (The phenomenon wherein everyone is descended from one person within what was once a tiny group of people is called founder effect.) The disease also occurs in members of families of other European, Arabic, and native American descent, but is less prevalent. Sjögren-Larsson syndrome affects both males and females.

Signs and symptoms

There are several signs and symptoms of Sjögren-Larsson syndrome. The major features of the disorder are the following:

Skin: In infancy, development of various degrees of scaling and reddened skin occurs (ichthyosis), often accompanied by hyperkeratosis (thickening of the skin) on the outer skin layer. After infancy, skin on the arms, legs, and abdomen is often dark and scaly and lacking redness. Bruises are present at birth or soon after.
Hair: Hair may be brittle.
Extremities: Joint contracture and hypertonia cause resistance of joints to movement and of muscles to stretching. Most individuals with the syndrome never walk.
Eyes: About half of the individuals with this syndrome have retinitis pigmentosa (pigmentary degeneration of the retina). Glistening white or yellow-white dots on the retina (ocular fundus) are characteristic. They may be an early sign of the disease, presenting at age 1–2, and may increase with age.
Nervous system: Spastic diplegia or tetraplegia (paralysis) affecting arms and/or legs. About half of the individuals with this disorder have seizures.
Urogenital system: Kidney diseases may be associated with this syndrome.
Growth and development: Individuals with the disorder tend to be unusually short in stature. Mental retardation is characteristic. Speech disorders may be present.

Speech abnormalities, mental retardation, and seizures usually occur during the first two or three years of life.

Diagnosis

The clinical features of Sjögren-Larsson syndrome are often distinctive, and a pattern of anomalies may suggest the diagnosis. In addition to ichthyosis and spasticity at birth, glistening white or yellow-white dots on the retina may be an early sign of the disease, presenting in the first or second year of life. If they occur, speech abnormalities, mental retardation, and seizures present during the first two or three years of life.

Laboratory findings are important in diagnosing Sjögren-Larsson syndrome. A laboratory test for deficiency of an enzyme (a protein that catalyzes chemical reactions in the human body) called fatty aldehyde dehydrogenase 10 (FALDH10) will determine presence of the disease. Sjögren-Larsson is due to a deficiency of FALDH10, and the gene for the Sjögren-Larsson syndrome is the same as the FALDH10 gene.

Positive laboratory results for Sjögren-Larsson will include the following findings:

Hexadeconal elevated in fibroblasts.
Fatty alcohol NAD+ deficient in drome fibroblasts. Sjögren-Larsson syndrome fibroblasts.
Fatty aldehyde dehydrogenase (FALDH) deficiency.

Genetic counseling

Individuals with a family history of Sjögren-Larsson syndrome may benefit from genetic counseling to learn about the condition including treatments, inheritance, testing, and options available to them so that they can make informed decisions appropriate to their families. A child with both parents who carry the Sjögren-Larsson gene mutation has a 25% chance having the disorder. Couples who have had one affected child have a 25% risk of having another child with the disorder in each pregnancy.

Prenatal testing

Families at risk to have a child with Sjögren-Larsson syndrome may have the option of prenatal diagnosis. DNA can be extracted from fetal cells obtained by either chorionic villus sampling (usually done until 12 weeks gestation) or amniocentesis (usually done at 16–18 weeks gestation) and tested to determine if the altered gene in the family is present. These techniques usually require that the alteration in the gene has been identified previously in an affected family member.

Chorionic villus sampling is a procedure to obtain chorionic villi tissue for testing. Chorionic villi are microscopic, finger-like projections that emerge from the chorionic membrane and eventually form the placenta. The cells of the chorionic villi are of fetal origin so laboratory analysis can identify a number of genetic abnormalities of the fetus. Because the villi are attached to the uterus, however, there is a chance that maternal tissue may be analyzed rather than the fetal cells. If the sample is too small, it may be necessary to repeat the procedure. In addition, the quality of the chromosome analysis is usually not as good with chorionic villus sampling as with amniocentesis. The chromosomes may not be as long, and so it may not be possible to identify some of the smaller bands on the chromosomes.

Amniocentesis is a procedure that involves inserting a thin needle into the uterus, into the amniotic sac, and withdrawing a small amount of amniotic fluid (a liquid produced by the fetal membranes and the fetus that surrounds the fetus throughout pregnancy). DNA can be extracted from the fetal cells contained in the amniotic fluid and tested for the specific mutation known to cause Sjögren-Larsson syndrome.

Treatment and management

Individuals with Sjögren-Larsson syndrome should be under routine health supervision by a physician who is familiar with the disorder, its complications, and its treatment. Supportive resources for individuals with Sjögren-Larsson syndrome and their families should be provided. Some clinical improvement has been reported to occur with fat restriction in the diet and supplementation with medium-chain triglycerides.

Other treatment of the disorder is generally symptomatic.

For dermatologic symptoms, various skin softening ointments are useful in reducing symptoms. Plain petroleum jelly may be effective, especially when applied while the skin is still moist, such as after bathing. Salicylic acid gel may also be effective. When using the ointment, skin is covered at night with an airtight, waterproof dressing. Lactate lotion is another effective treatment for the dermatologic symptoms.
For ocular symptoms, regular care from a qualified ophthalmologist is important.
To control seizures, anti-convulsant medications may be helpful.
Speech therapy and special education services may be helpful.

Prognosis

Prognosis is variable depending upon the severity of the disease. Sjögren-Larsson does not generally lead to shortened life span.

Resources

BOOKS

Medical Genetics, edited by Lynn B. Jorde, et al. 2nd ed. St. Louis: Mosby, 1999.

PERIODICALS

Rizzo, W.B. "Inherited Disorders of Fatty Alcohol Metabolism." Molecular Genetics and Metabolism (1998) 65: 63-73.

Rizzo, W.B., G. Carney, and Z. Lin. "The Molecular Basis of Sjögren-Larsson Syndrome: Mutation Analysis of the Fatty Aldehyde Dehydrogenase Gene." American Journal of Human Genetics 65 (December 1999): 1547-60.

Willemsen, M.A., et al. "Sjögren-Larsson Syndrome." Journal of Pediatrics 136 (February 2000): 261.

ORGANIZATIONS

Arc (a National Organization on Mental Retardation). 1010 Wayne Ave., Suite 650, Silver Spring, MD 20910. (800) 433-5255. <http://www.thearclink.org>.

Foundation for Ichthyosis and Related Skin Types. 650 N. Cannon Ave., Suite 17, Landsdale, PA 19446. (215) 631-1411 or (800) 545-3286. Fax: (215) 631-1413. <http://www.scalyskin.org>.

National Institute of Arthritis and Musculoskeletal and Skin Diseases. National Institutes of Health, One AMS Circle, Bethesda, MD 20892. <http://www.nih.gov/niams>.