Dermatologic Manifestations of Sjogren-Larsson Syndrome

Updated: Jul 19, 2017
  • Author: Robert A Schwartz, MD, MPH; Chief Editor: William D James, MD  more...
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Overview

Background

Sjögren-Larsson syndrome (SLS) is a rare autosomal recessive neurocutaneous disorder characterized by mental retardation, diplegia or tetraplegia, and congenital ichthyosis. The ichthyosis (usually evident at birth) may be seen in some patients after the first year of life. [1]

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Pathophysiology

Sjögren-Larsson syndrome (SLS) is due to deficient activity of fatty aldehyde dehydrogenase (FALDH), an enzyme required to oxidize fatty alcohol to fatty acid. This syndrome is a result of mutations in the gene that codes for fatty aldehyde dehydrogenase. [2, 3, 4, 5, 6] It catalyzes the oxidation of medium- and long-chain fatty aldehydes to their corresponding carboxylic acids.

The gene encoding FALDH is called the ALDH3A2 gene (or ALDH10) and has been mapped to the Sjögren-Larsson syndrome locus on band 17p11.2. FALDH is involved in the last step of the conversion of 22-hydroxy-C22:0 into the dicarboxylic acid of C22:0 (C22:0-DCA).

Current results show a large variety of mutant alleles carrying different mutations (>72), including amino acid substitutions, small and large contiguous gene deletions, insertions, and splicing errors in this gene. Most mutations are private, but many common mutations reflect founder effects, consanguinity, or recurrent mutationalevents. [7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17]

Beyond mutations, the neurologic and other phenotypic characteristics may result from unidentified epigenetic/environmental factors, gene modifiers, or other mechanisms. [2]

Accumulation of long-chain fatty alcohols and modification of macromolecules by an excess of fatty aldehydes are thought to be the pathophysiologic mechanisms causing the manifestations of Sjögren-Larsson syndrome. This accumulation may lead to alteration of the epidermal water barrier and increased transepidermal water loss, subsequently leading to ichthyosis. Permeability barrier abnormality localizes to the stratum corneum interstices and presents as abnormalities in lamellar body formation and secretion.

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Epidemiology

Frequency

United States

Detailed epidemiologic studies have not been conducted; however, in regions where the population is inbred, Sjögren-Larsson syndrome is much more common (eg, in the Haliwas of Halifax County and Warren County in North Carolina).

International

An unusually high incidence of patients with Sjögren-Larsson syndrome is observed in areas where consanguineous marriages are noted (eg, Vasterbotten County and Norrbotten County in Sweden, where a mutation was introduced around the 13th century).

The prevalence of patients with Sjögren-Larsson syndrome in northern Sweden is 8.3 cases per 100,000 births, whereas the prevalence of heterozygotes is 2% and the gene frequency is 0.01%. The overall incidence in Sweden is estimated to be around 0.6 cases per 100,000 births. A lower incidence (<1 case per 100,000 births) has been observed worldwide.

Sjögren-Larsson syndrome is estimated to be observed in 1 in every 1000 patients with mental retardation and in 1 in every 2500 pediatric dermatologic patients.

Race

No apparent racial predilection exists. Consanguinity seems to be the most important factor.

Sex

No sexual predilection exists.

Age

Newborns usually manifest symptoms and signs of Sjögren-Larsson syndrome (first ichthyosis, subsequently neurologic symptoms). The latter develop in patients aged 4-30 months. [18, 19]

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Prognosis

Sjögren-Larsson syndrome is not lethal. Patients with Sjögren-Larsson syndrome typically do not show a progressive neurodegenerative course. Most patients survive into adulthood.

After neurologic symptoms appear (age 1-2 y), the developmental milestones are progressively delayed. The initial ability to walk a short distance alone is lost, which is caused by progressive spasticity. No progression of the neurologic findings or mental retardation occurs after puberty. Symptoms tend to appear earlier in patients who will be more severely affected in the future.

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Patient Education

Active involvement of a third party (eg, parents, family) is mandatory for the continuous special care of patients with Sjögren-Larsson syndrome. Special schooling is necessary.

For patient education resources, see the patient education article Sjögren Syndrome.

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