eMedicine Specialties > Dermatology > Pediatric Diseases

Sjogren-Larsson Syndrome

Author: Anna Zalewska, MD, PhD, Assistant Professor, Adjunct Professor, Department of Dermatology and Venereology, Medical University of Lodz, Poland
Coauthor(s): Robert A Schwartz, MD, MPH, Professor and Head, Dermatology, Professor of Pathology, Pediatrics, Medicine, and Preventive Medicine and Community Health, UMDNJ-New Jersey Medical School
Contributor Information and Disclosures

Updated: Jun 19, 2009

Introduction

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.

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, 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

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.

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.11,12

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.

Clinical

History

Most Sjögren-Larsson syndrome (SLS) patients are born preterm and have erythema at birth.13 The diagnosis of Sjögren-Larsson syndrome is almost always delayed because only cutaneous symptoms (eg, scaling, hyperkeratosis) are usually present at birth.

  • A family history of siblings affected by Sjögren-Larsson syndrome or a consanguineous marriage of the parents is sometimes present.
  • Pruritus is a prominent feature that is not found in other types of ichthyosis.
  • Photophobia is a common complaint.
  • The skin gradually becomes thickened and scaly in the first year of life.
    • Desquamation of the palms and the soles is observed in some cases.
    • Later, a wrinkled brownish yellow hyperkeratosis gradually develops, with a predilection on the main flexor folds of the extremities.
    • Ichthyosis is seen at birth and worsens with time.
  • At first, the neurologic signs are nonspecific (eg, mental retardation, spasticity); however, severe neuromotor and mental developmental delay is usually obvious by the time the patient is aged 1-2 years. It gradually progresses to reach a plateau phase.
    • Neck posturing seems to be apparent by the time the patient is aged 3 years.
    • Involuntary jaw opening while eating is usually observed by the time the patient is aged 6 years.
    • Seizures usually develop later in childhood.

Physical

The key triad of symptoms for Sjögren-Larsson syndrome (SLS) includes nonbullous congenital ichthyosiform erythroderma, spastic diplegia or quadriplegia, and mental retardation. An additional group of signs comprises other dermatologic symptoms, ophthalmologic signs, speech defects, epilepsy, dental problems, and skeletal abnormalities.

  • Skin involvement (type of lesions)
    • Ichthyosis is generalized, with the trunk, the flexures, and the dorsal aspects of the hands and the feet most severely affected. It may present as fine, furfuraceous (dandrufflike) scaling; lamellar-type hyperkeratosis with thin scales; or nonscaly thickening in the stratum corneum.
    • A yellow discoloration may occur with extensive thickening of the skin and is mostly pronounced around the umbilicus and the main flexures.
    • The face is mostly spared.
    • Hair and nails are usually normal.
    • Dermatoglyphic alterations (eg, simian creases, palmar hyperlinearity) may be present.
  • Dental findings: Enamel hypoplasia may be present.
  • Skeletal findings14 : Skeletal abnormalities (eg, short stature, kyphoscoliosis) may be observed.
  • Neurologic signs15,16
    • Spasticity may be apparent before age 3 years and is more severe in the lower limbs than in other parts of the body.
    • Mental retardation is moderate to severe and mostly progressive (intelligence quotient [IQ] <50 in about 70% of patients).
    • Seizures (epilepsy) occur in about 30-50% of patients with Sjögren-Larsson syndrome.
    • Delayed or impaired speech may be present.
    • Hyperreflexia (tendon reflexes) is increased, and a positive bilateral Babinski reflex may occur.
    • Joint hyperextensibility may be observed.
  • Ophthalmologic signs
    • Glistening dots on the macular region of the retina are pathognomonic for Sjögren-Larsson syndrome.
    • Other ophthalmologic findings include subnormal visual acuity, conjunctivitis, blepharitis, punctate erosions of the cornea, and fundus autoreflectance changes.17

Causes

Sjögren-Larsson syndrome (SLS) is caused by a heterogenous group of mutations in the ALDH3A2 gene, which encodes FALDH and is located on band 17p11.2. The ALDH10 gene consists of 11 exons and is widely expressed in tissues.

  • Sjögren-Larsson syndrome is due to a genetic block in the oxidation of fatty alcohol to fatty acid because of deficient activity of FALDH, a component of the fatty alcohol:NAD oxidoreductase enzyme complex (FAO).
  • FALDH catalyzes the oxidation of medium- and long-chain (aliphatic) fatty aldehydes derived from fatty alcohols.

More on Sjogren-Larsson Syndrome

Overview: Sjogren-Larsson Syndrome
Differential Diagnoses & Workup: Sjogren-Larsson Syndrome
Treatment & Medication: Sjogren-Larsson Syndrome
Follow-up: Sjogren-Larsson Syndrome
References
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References

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  15. Akdeniz N, Calka O, Anlar O, et al. Report of a Turkish child with Sjogren-Larsson syndrome associated with peripheral nerve involvement. J Dermatol. Mar 2003;30(3):222-5. [Medline].

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  30. Gloerich J, Ijlst L, Wanders RJ, Ferdinandusse S. Bezafibrate induces FALDH in human fibroblasts; implications for Sjogren-Larsson syndrome. Mol Genet Metab. Sep-Oct 2006;89(1-2):111-5. [Medline].

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Further Reading

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Keywords

Sjögren-Larsson syndrome, Sjogren-Larsson syndrome, SLS, neurocutaneous disorder

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Contributor Information and Disclosures

Author

Anna Zalewska, MD, PhD, Assistant Professor, Adjunct Professor, Department of Dermatology and Venereology, 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, UMDNJ-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.

Medical Editor

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 Salary Employment; Orfagen Consulting fee Consulting; Maruho Consulting fee Consulting; Astellas Consulting fee Consulting

Pharmacy Editor

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.

Managing Editor

Jeffrey P Callen, MD, Professor of Medicine, 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 Honoraria Consulting; Centocor Honoraria Consulting; Genetech Honoraria Consulting; Celgene Honoraria Consulting

CME Editor

Catherine Quirk, MD, Clinical Assistant Professor, Department of Dermatology, Brown University
Catherine Quirk, MD is a member of the following medical societies: Alpha Omega Alpha and American Academy of Dermatology
Disclosure: Nothing to disclose.

Chief Editor

Dirk M Elston, MD, Director, Department of Dermatology, Geisinger Medical Center
Dirk M Elston, MD is a member of the following medical societies: American Academy of Dermatology
Disclosure: Nothing to disclose.

 
 
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