Syndrome, Sjogren-Larsson

The Sjogren-Larsson syndrome is a genetic (inherited) disease usually characterized by a triad of clinical findings consisting of ichthyosis (thickened fish-like skin), spastic paraplegia (spasticity of the legs) and mental retardation. The skin changes in the Sjogren-Larsson syndrome are similar to those in congenital ichthyosiform erythroderma, a genetic disease that results in fish-like, reddened skin. Hyperkeratosis (thickening of the skin) is a regular feature. Ecchymoses (bruises) are present at birth or soon after in the Sjogren-Larsson syndrome. Sweating is normal. The spasticity can also affect the arms as well as the legs, resulting in spastic paraplegia. The mental retardation is significant. Most of the patients never walk. About half the patients have seizures. Eye problems are also part of the syndrome. About half of cases have pigmentary degeneration of the retina. Glistening white dots on the retina are characteristic. People with Sjogren-Larsson syndrome tend to be unusually short. Sjogren in 1956 (and Sjogren and Larsson in 1957) suggested that all Swedes with the syndrome are descended from one ancestor in whom a mutation (a genetic change) occurred about 600 years ago. This mutation is now present in at least 1% of the population in northern Sweden. This phenomenon is called founder effect (because everyone is descended from one "founder" within what was once a tiny group of people). The gene for the Sjogren-Larsson syndrome has been found situated on chromosome number 17 (in band 17p11.2). The presence in a person of one copy of the gene (the heterozygous state) is harmless. However, if two gene carriers (heterozygotes) mate, the risk for each of their children is one-quarter to receive both of their Sjorgren-Larsson genes and to have the syndrome. The inheritance of Sjogren-Larsson syndrome is thus termed autosomal (non-sexlinked) recessive. The laboratory findings are critically important. There is a deficiency of an enzyme called fatty aldehyde dehydrogenase 10 (FALDH10)in the Sjogren-Larsson syndrome. The syndrome is due to a deficit of FALDH10 and the gene for the Sjogren-Larsson syndrome gene is synonymous with the FALDH10 gene. Some clinical improvement has been reported to occur with fat restriction in the diet and supplementation with medium-chain triglycerides. Persons of diverse and different ethnic origins are now known with the Sjogren-Larsson syndrome. They include not only Swedes but, for example, members of families of other European, Arabic, and native American (AmerIndian) descent. This is evidence for genetic homogeneity (what appears clinically to be one genetic disease is in reality due to a diversity of mutations. All of the mutations causing Sjogren-Larsson syndrome have proved to be changes in the FALDH gene. The Sjogren-Larsson syndrome is sometimes called the T. Sjogren syndrome to distinguish it from the sicca syndrome, which was described by Henrick Sjogren, a Swedish ophthalmologist. The Sjogren of the Sjorgren-Larsson syndrome was Torsten Sjogren (1896-1974), professor of psychiatry at the celebrated Karolinska Hospital in Stockholm and a pioneer in modern psychiatry and medical genetics. Tage Larsson was similarly a Swedish physician. The Sjogren-Larsson syndrome is also known as SLS; the ichthyosis, spastic neurologic disorder, and oligophrenia (an old word for mental retardation) syndrome; fatty alcohol: NAD+ oxidoreductase deficiency (FAO deficiency); fatty aldehyde dehydrogenase deficiency (FALDH deficiency); or fatty aldehyde dehydrogenase 10 deficiency (FALDH10 deficiency). `