Dermatologic Manifestations of Sjogren-Larsson Syndrome 

  • Author: Anna Zalewska, MD, PhD; Chief Editor: William D James, MD   more...
 
Updated: Aug 17, 2011
 

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. Also see the eMedicine Pediatrics article Sjögren-Larsson Syndrome.

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

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.

Defective metabolism of leukotriene B4 (LTB4) is the first biochemical pathway demonstrated to be distorted in patients with Sjögren-Larsson syndrome. Distorted inactivation of LTB4 might form one of the mediator pathways responsible for considerable pruritus in patients with Sjögren-Larsson syndrome.[12, 13]

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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, Dermatology, Professor of Pathology, Pediatrics, Medicine, and Preventive Medicine and Community Health, University of Medicine and Dentistry of New Jersey-New Jersey Medical School

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

Disclosure: Nothing to disclose.

Specialty Editor Board

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: Stiefel GSK Company Salary Employment; Orfagen Consulting fee Consulting; Maruho Consulting fee Consulting; Astellas Consulting fee Consulting; Abbott Consulting fee Consulting; Leo Pharma Consulting fee Consulting

David F Butler, MD  Professor of Dermatology, Texas A&M University College of Medicine; Chair, Department of Dermatology, Director, Dermatology Residency Training Program, Scott and White Clinic, Northside Clinic

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

Disclosure: Amgen Honoraria Consulting; Abbott Honoraria Consulting; Electrical Optical Sciences Consulting fee Consulting; Celgene Honoraria Safety Monitoring Committee; GSK - Glaxo Smith Kline Consulting fee Consulting; TenXBioPharma Consulting fee Safety Monitoring Committee

Catherine M Quirk, MD  Clinical Assistant Professor, Department of Dermatology, University of Pennsylvania

Catherine M Quirk, MD is a member of the following medical societies: Alpha Omega Alpha and American Academy of Dermatology

Disclosure: Nothing to disclose.

Chief Editor

William D James, MD  Paul R Gross Professor of Dermatology, University of Pennsylvania School of Medicine; Vice-Chair, Program Director, Department of Dermatology, University of Pennsylvania Health System

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

Disclosure: Elsevier Royalty Other

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