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Dermatologic Manifestations of Sjogren-Larsson Syndrome

  • Author: Anna Zalewska, MD, PhD; Chief Editor: William D James, MD  more...
 
Updated: Sep 18, 2013
 

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.

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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.[1] 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.[2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12]

Beyond mutations, the neurologic and other phenotypic characteristics may result from unidentified epigenetic/environmental factors, gene modifiers, or other mechanisms.[1]

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.

Mortality/Morbidity

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

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.

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Contributor Information and Disclosures
Author

Anna Zalewska, MD, PhD Professor of Dermatology and Venereology, Psychodermatology Department, Chair of Clinical Immunology and Microbiology, Medical University of Lodz, Poland

Disclosure: Nothing to disclose.

Coauthor(s)

Robert A Schwartz, MD, MPH Professor and Head of Dermatology, Professor of Pathology, Pediatrics, Medicine, and Preventive Medicine and Community Health, Rutgers New Jersey Medical School; Visiting Professor, Rutgers University School of Public Affairs and Administration

Robert A Schwartz, MD, MPH is a member of the following medical societies: Alpha Omega Alpha, New York Academy of Medicine, American Academy of Dermatology, American College of Physicians, Sigma Xi

Disclosure: Nothing to disclose.

Specialty Editor Board

David F Butler, MD Section Chief of Dermatology, Central Texas Veterans Healthcare System; Professor of Dermatology, Texas A&M University College of Medicine; Founding Chair, Department of Dermatology, Scott and White Clinic

David F Butler, MD is a member of the following medical societies: American Medical Association, Alpha Omega Alpha, Association of Military Dermatologists, American Academy of Dermatology, American Society for Dermatologic Surgery, American Society for MOHS Surgery, Phi Beta Kappa

Disclosure: Nothing to disclose.

Jeffrey P Callen, MD Professor of Medicine (Dermatology), Chief, Division of Dermatology, University of Louisville School of Medicine

Jeffrey P Callen, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American College of Physicians, American College of Rheumatology

Disclosure: Received income in an amount equal to or greater than $250 from: XOMA; Biogen/IDEC; Novartis; Janssen Biotech, Abbvie, CSL pharma<br/>Received honoraria from UpToDate for author/editor; Received honoraria from JAMA Dermatology for associate editor and intermittent author; Received royalty from Elsevier for book author/editor; Received dividends from trust accounts, but I do not control these accounts, and have directed our managers to divest pharmaceutical stocks as is fiscally prudent from Stock holdings in various trust accounts include some pharmaceutical companies and device makers for i inherited these trust accounts; for: Celgene; Pfizer; 3M; Johnson and Johnson; Merck; Abbott Laboratories; AbbVie; Procter and Gamble; Amgen.

Chief Editor

William D James, MD Paul R Gross Professor of Dermatology, Vice-Chairman, Residency Program Director, Department of Dermatology, University of Pennsylvania School of Medicine

William D James, MD is a member of the following medical societies: American Academy of Dermatology, Society for Investigative Dermatology

Disclosure: Nothing to disclose.

Additional Contributors

Jacek C Szepietowski, MD, PhD Professor, Vice-Head, Department of Dermatology, Venereology and Allergology, Wroclaw Medical University; Director of the Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Poland

Disclosure: Received consulting fee from Orfagen for consulting; Received consulting fee from Maruho for consulting; Received consulting fee from Astellas for consulting; Received consulting fee from Abbott for consulting; Received consulting fee from Leo Pharma for consulting; Received consulting fee from Biogenoma for consulting; Received honoraria from Janssen for speaking and teaching; Received honoraria from Medac for speaking and teaching; Received consulting fee from Dignity Sciences for consulting; .

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