Rare Dermatology News

Disease Profile

Sjogren-Larsson syndrome

Prevalence
Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.
1-9 / 1 000 000

331 - 2,979

US Estimated

1-9 / 1 000 000

514 - 4,622

Europe Estimated

Age of onset

Infancy

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ICD-10

Q87.1

Inheritance

Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease

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Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype

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X-linked
dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

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X-linked
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder

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Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

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Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

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Not applicable

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Other names (AKA)

SLS; Fatty aldehyde dehydrogenase deficiency; FALDH deficiency;

Categories

Congenital and Genetic Diseases; Eye diseases; Metabolic disorders;

Summary

Sjogren-Larsson syndrome (SLS) is an inborn error of lipid metabolism, characterized by congenital ichthyosis (dry, scaly skin), intellectual disability, and spasticity (stiffness and involuntary muscle spasms). The syndrome is caused by mutations in the gene called FADH (fatty aldehyde dehydrogenase) and is inherited in an autosomal recessive fashion. Treatment is symptomatic.[1][2]

Symptoms

The signs and symptoms of SLS typically occur within the first two years of life. A primary feature of SLS is dry, scaly skin, which is called ichthyosis. In addition to ichthyosis, people can develop some or all of the following symptoms [1][2]:

  • Developmental delay
  • Intellectual disability
  • Speech difficulties
  • Seizures
  • Spastic diplegia/tetraplegia paralysis (diplegia is paralysis of both legs; tetraplegia is paralysis of all four limbs)
  • Spasticity in the legs: leg spasms, which can impair motor abilities and waking
  • Glistening white dots in the retina of the eye
  • Pruritus (itching)
  • Preterm birth

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

Medical Terms Other Names
Learn More:
HPO ID
80%-99% of people have these symptoms
Abnormal pyramidal sign
0007256
Dry skin
0000958
Erythema
0010783
Hyperkeratosis
0000962
Ichthyosis
0008064
Intellectual disability
Mental deficiency
Mental retardation
Mental retardation, nonspecific
Mental-retardation

[ more ]

0001249
Kyphosis
Hunched back
Round back

[ more ]

0002808
Skeletal dysplasia
0002652
Spastic diplegia
0001264
30%-79% of people have these symptoms
Abnormality of retinal pigmentation
0007703
Corneal erosion
Damage to outer layer of the cornea of the eye
0200020
Dysarthria
Difficulty articulating speech
0001260
Generalized hyperpigmentation
0007440
Inflammatory abnormality of the eye
0100533
Macular degeneration
0000608
Myopia
Close sighted
Near sighted
Near sightedness
Nearsightedness

[ more ]

0000545
Photophobia
Extreme sensitivity of the eyes to light
Light hypersensitivity

[ more ]

0000613
Retinopathy
Noninflammatory retina disease
0000488
Seizure
0001250
5%-29% of people have these symptoms
Abnormality of dental enamel
Abnormal tooth enamel
Enamel abnormalities
Enamel abnormality

[ more ]

0000682
Joint stiffness
Stiff joint
Stiff joints

[ more ]

0001387
Microcephaly
Abnormally small skull
Decreased circumference of cranium
Decreased size of skull
Reduced head circumference
Small head circumference

[ more ]

0000252
Muscular hypotonia
Low or weak muscle tone
0001252
Scoliosis
0002650
Short stature
Decreased body height
Small stature

[ more ]

0004322
Urticaria
Hives
0001025
Percent of people who have these symptoms is not available through HPO
Autosomal recessive inheritance
0000007
CNS demyelination
0007305
Hypoplasia of dental enamel
Underdeveloped teeth enamel
0006297
Opacification of the corneal epithelium
0007727
Retinal pigment epithelial atrophy
0007722
Retinal thinning
0030329
Spasticity
Involuntary muscle stiffness, contraction, or spasm
0001257
Thoracic kyphosis
0002942

Cause

SLS is caused mutations in the FADH (fatty aldehyde dehydrogenase) gene, which is located on chromosome 17 on the p arm at band 11.2. The enzyme made by the FADH gene is responsible for breaking down certain molecules called mediumand long-chain fatty aldehydes. If FADH is not functioning properly, these and related molecules build up in the body, specifically the membranes of the skin and brain, leading to the symptoms associated with SLS.[1][2]

Diagnosis

SLS can be diagnosed by a biochemical blood test that determines if FADH activity is normal. In addition, because mutations in FADH are known to cause SLS, the gene can be sequenced in order to determine if any mutations are present. This also provides the option of genetic and prenatal testing, which can allow parents to make informed decisions about having children.[1][2]

Testing Resources

  • The Genetic Testing Registry (GTR) provides information about the genetic tests for this condition. The intended audience for the GTR is health care providers and researchers. Patients and consumers with specific questions about a genetic test should contact a health care provider or a genetics professional.

    Treatment

    Topical application of various agents have been used to treat the ichthyosis.[2] Some clinical studies have found that a drug called zileuton can be beneficial in the treatment of SLS. In these studies, the drug successfully reduced the severity of the pruritis (itching), and improved the behavior of the treated child. While this drug does not cure SLS, it has the potential to greatly improve the quality of life of children with SLS.[1] Seizures usually respond well to anti-convulsant medications and spasticity is improved with surgery. Diets supplemented with medium-chain fatty acids have been reported to improve the skin, but the results are inconsistent.[2]

    More detailed information about treatment options for SLS can be accessed through the Treatment and Medication sections of Medscape Reference.

    Organizations

    Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

    Organizations Supporting this Disease

      Organizations Providing General Support

        Learn more

        These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

        Where to Start

        • DermNetNZ provides information on ichthyosis in general. DermNetNZ is an online resource about skin diseases developed by the New Zealand Dermatological Society Incorporated.
        • Genetics Home Reference (GHR) contains information on Sjogren-Larsson syndrome. This website is maintained by the National Library of Medicine.
        • The National Organization for Rare Disorders (NORD) has a report for patients and families about this condition. NORD is a patient advocacy organization for individuals with rare diseases and the organizations that serve them.

          In-Depth Information

          • Medscape Reference provides information on this topic. You may need to register to view the medical textbook, but registration is free.
          • The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
          • Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine. 
          • Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
          • PubMed is a searchable database of medical literature and lists journal articles that discuss Sjogren-Larsson syndrome. Click on the link to view a sample search on this topic.

            References

            1. Sjogren-Larsson Syndrome. United Leukodystrophy Foundation. https://ulf.org/sjogren-larsson-syndrome. Accessed 9/21/2012.
            2. Rizzo WB. Sjogren-Larsson Syndrome: Molecular Genetics and Biochemical Pathogenesis of Fatty Aldehyde Dehydrogenase Deficiency. Mol Genet Metab. September 22, 2006; https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1933507/?tool=pubmed. Accessed 9/21/2012.

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