Description
Sjögren-Larsson syndrome is a condition that affects the skin and eyes as well as the brain and spinal cord (central nervous system).
Infants with Sjögren-Larsson syndrome tend to be born prematurely. At birth, the skin may be thicker than normal (hyperkeratosis) and red (erythema), but it typically becomes dry and scaly (ichthyosis). Mild to severe itchiness (pruritus) is also common. The skin abnormalities generally affect the neck, torso, arms, and legs. The face is usually not affected.
Tiny crystals in the light-sensitive tissue at the back of the eye (retina
) can be seen during an eye exam in most affected individuals who are older than 3 to 4 years of age. This feature is unique to people with Sjögren-Larsson syndrome and can be used to diagnose the condition. These retinal crystals are often called “glistening white dots.” People with Sjögren-Larsson syndrome may also have nearsightedness (myopia
) or an increased sensitivity to light (photophobia).
People with Sjögren-Larsson syndrome may have neurological signs and symptoms. Affected individuals often have leukoencephalopathy, which is a change in a type of brain tissue called white matter. White matter consists of nerve fibers
that are covered by a substance (myelin) that insulates and protects the nerves. Leukoencephalopathy is thought to contribute to many of the neurological signs and symptoms seen in people with Sjögren-Larsson syndrome.
Most people with Sjögren-Larsson syndrome have intellectual disabilities, which can vary from mild to severe. Speech difficulties (dysarthria) are common, and speech development is often delayed. Affected individuals typically have more trouble speaking than understanding language. Approximately 35 to 40 percent of people with Sjögren-Larsson syndrome have seizures.
Children with Sjögren-Larsson syndrome typically experience abnormal muscle stiffness (spasticity) in their legs and, less commonly, in their arms. The spasticity may cause a delay in the development of motor skills such as sitting, crawling, and walking. Joint deformities (contractures) are also common. Approximately 50 percent of people with Sjögren-Larsson syndrome will require wheelchair assistance.
Frequency
Sjögren-Larsson syndrome affects approximately 1 in 100,000 individuals in Sweden, where the disease was first identified. Although this disease is found all over the world, the prevalence of Sjögren-Larsson syndrome in other countries is unknown.
Causes
Variants (also called mutations) in the ALDH3A2 gene cause Sjögren-Larsson syndrome. The ALDH3A2 gene provides instructions for making an enzyme that is part of a multistep process called fatty acid oxidation in which fats are broken down and converted into energy. Specifically, the ALDH3A2 enzyme breaks down molecules called fatty aldehydes into fatty acids.
Variants in the ALDH3A2 gene can cause cells to produce a version of the ALDH3A2 enzyme that is unable to break down fatty aldehyde molecules. As a result, fat molecules build up inside the cell. Within skin cells, the accumulation of fat molecules disrupts the structure and function of cell membranes. Because cell membranes act as protective barriers, these impaired skin cells cannot control fluid loss, which contributes to the dry and scaly skin seen in people with Sjögren-Larsson syndrome.
In the brain, the accumulation of fat molecules likely disrupts the structure and function of myelin, which acts as a protective barrier for nerve cells. Because myelin plays an important role in the transmission of nerve impulses, these changes likely lead to the intellectual disabilities and developmental delays seen in people with Sjögren-Larsson syndrome.
Inheritance
This condition is inherited in an autosomal recessive pattern
, which means both copies of the gene in each cell must have a variant to cause the disorder. The parents of an individual with an autosomal recessive condition each carry one copy of the altered gene, but they typically do not show signs and symptoms of the condition.
Other Names for This Condition
- FALDH deficiency
- Fatty acid alcohol oxidoreductase deficiency
- Fatty alcohol-nicotinamide adenine dinucleotide oxidoreductase deficiency
- Fatty aldehyde dehydrogenase deficiency
- Ichthyosis oligophrenia syndrome
- Ichthyosis, spastic neurologic disorder, and oligophrenia
- Sjogren-Larsson syndrome
- SLS
Additional Information & Resources
Genetic Testing Information
Genetic and Rare Diseases Information Center
Patient Support and Advocacy Resources
Clinical Trials
Catalog of Genes and Diseases from OMIM
Scientific Articles on PubMed
References
- Bindu PS. Sjogren-Larsson Syndrome: Mechanisms and Management. Appl Clin Genet. 2020 Jan 7;13:13-24. doi: 10.2147/TACG.S193969. eCollection 2020. Citation on PubMed
- Fuijkschot J, Theelen T, Seyger MM, van der Graaf M, de Groot IJ, Wevers RA, Wanders RJ, Waterham HR, Willemsen MA. Sjogren-Larsson syndrome in clinical practice. J Inherit Metab Dis. 2012 Nov;35(6):955-62. doi: 10.1007/s10545-012-9518-6. Epub 2012 Jul 26. Citation on PubMed
- Ganemo A, Jagell S, Vahlquist A. Sjogren-larsson syndrome: a study of clinical symptoms and dermatological treatment in 34 Swedish patients. Acta Derm Venereol. 2009;89(1):68-73. doi: 10.2340/00015555-0561. Citation on PubMed
- Jagell S, Gustavson KH, Holmgren G. Sjogren-Larsson syndrome in Sweden. A clinical, genetic and epidemiological study. Clin Genet. 1981 Apr;19(4):233-56. doi: 10.1111/j.1399-0004.1981.tb00704.x. Citation on PubMed
- Lossos A, Khoury M, Rizzo WB, Gomori JM, Banin E, Zlotogorski A, Jaber S, Abramsky O, Argov Z, Rosenmann H. Phenotypic variability among adult siblings with Sjogren-Larsson syndrome. Arch Neurol. 2006 Feb;63(2):278-80. doi: 10.1001/archneur.63.2.278. Citation on PubMed or Free article on PubMed Central
- Rizzo WB, S'Aulis D, Jennings MA, Crumrine DA, Williams ML, Elias PM. Ichthyosis in Sjogren-Larsson syndrome reflects defective barrier function due to abnormal lamellar body structure and secretion. Arch Dermatol Res. 2010 Aug;302(6):443-51. doi: 10.1007/s00403-009-1022-y. Epub 2010 Jan 5. Citation on PubMed or Free article on PubMed Central
- Rizzo WB. Genetics and prospective therapeutic targets for Sjogren-Larsson Syndrome. Expert Opin Orphan Drugs. 2016 Apr;4(4):395-406. doi: 10.1517/21678707.2016.1154453. Epub 2016 Mar 10. Citation on PubMed
- Rizzo WB. Sjogren-Larsson syndrome: molecular genetics and biochemical pathogenesis of fatty aldehyde dehydrogenase deficiency. Mol Genet Metab. 2007 Jan;90(1):1-9. doi: 10.1016/j.ymgme.2006.08.006. Epub 2006 Sep 22. Citation on PubMed or Free article on PubMed Central
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