Edit concept Question Editor Create issue ticket

Sjögren-Larsson Syndrome

Sjogren-Larsson Syndrome

Sjögren-Larsson syndrome is a genetic disorder of lipid metabolism characterized by a triad of ichthyosis apparent at birth, spastic paraplegia, and mild-to-moderate intellectual impairment.


Presentation

Most patients with Sjögren-Larsson syndrome (SLS) usually present within the first few years after birth. However, there is no correlation between disease severity and increasing age in adults [1]. In addition, studies have demonstrated phenotypic heterogeneity occurring even within affected families, with some children manifesting a less severe form of the disease [2].

The usual clinical spectrum consists of cutaneous, neurological and ocular symptoms [2]. The severity of the dermatological features is in not related to the neurological symptomatology.

Patients usually present with skin manifestations as the earliest form of the disease, with skin erythema dominating at birth. The lack of keratinization leaves the skin dry and scaly, with a brown-to-yellow discoloration. The most common sites involved are usually the flexor aspects of the extremities, neck, umbilicus and axilla, with the face being largely unaffected. Pruritus is almost always present in patients with SLS [3].

Neurological symptoms present as motor deficits in the first 2 years of life, with the legs being more commonly involved than the arms [2]. The spasticity may lead to the development of joint contractures. Patients, though being able to walk, are quickly wheelchair-bound in adolescence.

A delay in developmental milestones and mental retardation characterize the cognitive deficits found in SLS. Acquired skills are usually intact in these patients. The motor and cognitive deficits may contribute to speech abnormalities in these patients, with pseudobulbar dysarthria seen as a significant finding [2].

SLS in early childhood may also cause retinal crystals to develop in the foveal regions, contributing to the loss of visual acuity. Photophobia is another common finding [2].

Other features may include seizures, premature births and short stature [2] [4].

Short Stature
  • Less common features are retinal changes, short stature, kyphoscoliosis, preterm birth, photophobia, reduction of visual acuity, seizures, and delayed speech.[ncbi.nlm.nih.gov]
  • Associated disorders may be sparse and brittle hair, short stature, pigmentary retinal degeneration, seizures, hypohidrosis, dysplasia of dental enamel, kyphosis, hypertelorism, and metaphyseal dysplasia with small irregular epiphyses.[whonamedit.com]
  • Other features may include seizures, premature births and short stature. SLS may be missed in early infancy or childhood, owing to the occult nature and diminished severity of clinical features.[symptoma.com]
  • Sjögren-Larsson syndrome An autosomal recessive condition (OMIM:270200) characterised by ichthyosiform erythroderma, spastic paralysis, mental retardation, retinal degeneration, sparse and brittle hair, enamel hypoplasia, short stature, ocular hypertelorism[medical-dictionary.thefreedictionary.com]
Dysphagia
  • By 19 years of age, she had developed dysphagia and became completely dependent on others for most activities of daily living.[ncbi.nlm.nih.gov]
Spastic Paraplegia
  • The Sjogren-Larsson syndrome is a neurocutaneous, autosomal recessive and disabling condition, characterized by congenital ichthyosis, spastic paraplegia and mental retardation.[ncbi.nlm.nih.gov]
  • Marinesco-Sjögren-Garland syndrome - see under Marinesco Marinesco-Sjögren syndrome - see under Marinesco Sjögren-Larsson syndrome - congenital ichthyosis in association with oligophrenia and spastic paraplegia.[medical-dictionary.thefreedictionary.com]
  • Case 2 A 7-year-old boy presented with ichthyosis and spastic paraplegia. He was born a month preterm, of a consanguineous marriage. Ichthyosis had been present since birth.[ijdvl.com]
  • SLS (Sjogren-Larsson syndrome): The Sjogren-Larsson syndrome is a genetic (inherited) disease usually characterized by a triad of clinical findings consisting of ichthyosis (thickened fish-like skin), spastic paraplegia (spasticity of the legs) and mental[medicinenet.com]
Dystonia
  • This report highlights a unique clinical feature of Sjogren-Larsson syndrome with progressive neurodegeneration associated with dystonia and tremor.[ncbi.nlm.nih.gov]
  • Dystonia secondary to Sjogren-Larsson syndrome. Neurology. 2000 Oct 24. 55(8):1236-7. [Medline]. Mirshahi A, Piri N. Fundus autofluorescence changes in two cases of Sjogren-Larsson syndrome. Int Ophthalmol. 2008 Oct 2.[emedicine.com]
Spastic Paralysis
  • Larsson, twentieth-century Swedish pediatrician a congenital condition inherited as an autosomal-recessive trait, characterized by ichthyosis, mental deficiency, and spastic paralysis.[medical-dictionary.thefreedictionary.com]
  • Other characteristics include congenital ichtyosis or ichtyosiform erythroderma, and spastic paralysis.[whonamedit.com]
  • Spastic paralysis, impairment of intelligence, and other neurologic changes were usually present.[jamanetwork.com]
Cognitive Deficit
  • The motor and cognitive deficits may contribute to speech abnormalities in these patients, with pseudobulbar dysarthria seen as a significant finding.[symptoma.com]

Workup

SLS may be missed in early infancy or childhood, owing to the occult nature and diminished severity of clinical features.

The definitive diagnosis of SLS is made by the demonstration of reduced activity of fatty aldehyde dehydrogenase (FALDH) (less than 15% of normal value) in skin fibroblasts or white blood cells [5].

In addition, mutations in the ALDH3A2 gene (that codes for FALDH) may be detected via genetic analyses. Amniocentesis or chorionic villus sampling may help in prenatal diagnosis by demonstrating reduced activity of FALDH in amniocytes and cultured chorionic villi cells respectively [6].

Delayed myelination may be diagnosed by magnetic resonance imaging (MRI) in patients with SLS, usually presenting as hyperintensities in the periventricular areas on T2-weighted images [7]. Magnetic resonance spectroscopy (MRS) may be useful to show high lipid densities in the white matter around the ventricles. Gliosis is another significant finding seen on MRS [8].

Gross examination of brain sections shows diffuse atrophy with gliosis, without any significant axonal loss. The lack of myelin may be seen in the cerebral and cerebellar white matter regions [9].

Lipid deposits may also be seen on microscopy in subpial and subependymal glial cell layers, with the brainstem being involved in a few cases. Breakdown products of lipids (in the form of lipofuscin-laden macrophages) and astrocytes (in the form of ellipsoid bodies) are usually seen in SLS. Axonal injury, represented by spheroid bodies, are also noted to occur [10].

Dyslipidemia
  • […] prominent neurologics signs, unclassified primitive or secondary maculopathy, metabolic disease with cataract, metabolic disease with pigmentary retinitis, syndromic ichthyosis associated with ocular features, hereditary retinal dystrophy, syndromic dyslipidemia[commons.wikimedia.org]

Treatment

  • The current treatment of spasticity in patients with Sjögren-Larsson syndrome is largely symptomatic, given that no effective causal therapy treatments are available.[ncbi.nlm.nih.gov]
  • The material is in no way intended to replace professional medical care by a qualified specialist and should not be used as a basis for diagnosis or treatment.[orpha.net]

Prognosis

  • Neuroradiological examinations, including CT, are of no practical value at present for the diagnosis, therapy or prognosis of the disease.[ncbi.nlm.nih.gov]
  • Prognosis Patients usually survive until adulthood but require life-long care. No progression of the neurologic findings or intellectual deficit occurs after puberty. Patients with early symptoms tend to be more severely affected.[orpha.net]
  • Prognosis - Sjögren-Larsson syndrome Not supplied. Treatment - Sjögren-Larsson syndrome Topical application of various agents have been used to treat the ichthyosis.[checkorphan.org]

Etiology

  • Etiology SLS is caused by mutations in the ALDH3A2 gene (17p11.2) encoding fatty aldehyde dehydrogenase (FALDH), an enzyme that catalyzes the oxidation of fatty aldehydes to fatty acids.[orpha.net]
  • Etiology 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.[emedicine.com]

Epidemiology

  • Summary Epidemiology Prevalence is estimated at 1/250,000 worldwide, but the syndrome is more common in Sweden due to a founder effect. Clinical description Clinical features develop prenatally and during infancy.[orpha.net]
  • 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[emedicine.com]
Sex distribution
Age distribution

Pathophysiology

  • Author information 1 Department of Pediatrics, Radboud University Medical Centre, Nijmegen, The Netherlands. j.fuijkschot@cukz.umcn.nl Abstract This review article gives a state-of-the-art synopsis of current pathophysiological concepts in Sjögren-Larsson[ncbi.nlm.nih.gov]
  • Defective fatty alcohol oxidation because of deficiency of fatty aldehyde dehydrogenase (FALDH) is the underlying pathophysiologic mechanism that gives rise to the symptoms.2,3 There also is evidence of defective leukotriene B4 (LTB4) degradation caused[mdedge.com]
  • The ichthyosis (usually evident at birth) may be seen in some patients after the first year of life. [1, 2] Pathophysiology Sjögren-Larsson syndrome (SLS) is due to deficient activity of fatty aldehyde dehydrogenase (FALDH), an enzyme required to oxidize[emedicine.com]

Prevention

  • Congenital icthyosis mental retardation spasticity syndrome, Ichthyosis oligophrenia syndrome, Fatty aldehyde dehydrogenase deficiency, FALDH deficiency, FADH deficiency, FAO deficiency Symptoms - Sjögren-Larsson syndrome Causes - Sjögren-Larsson syndrome Prevention[checkorphan.org]
  • It has been noted that administration of aldehyde traps has the potential to treat active disease, prevent disease, and slow progression of chronic disease.[raredr.com]
  • By sequestering fatty aldehydes when applied topically to the skin, reproxalap could significantly lower RASP levels - thereby preventing lipid modification and the ensuing moisture barrier dysfunction that causes ichthyosis in SLS patients.[aldeyra.com]
  • Patients with Sjögren-Larsson syndrome typically benefit from regular physical therapy to maintain ambulation and to prevent contractures from progressing.[emedicine.medscape.com]
  • Most patients show generalized ichthyosis, mild to moderate mental retardation, and spastic diplegia that often prevents or impedes walking.[ommbid.mhmedical.com]

References

Article

  1. Lossos A, Khoury M, Rizzo WB, et al. Phenotypic variability among adult siblings with Sjögren-Larsson syndrome. Arch Neurol. 2006; 63:278.
  2. van Domburg PH, Willemsen MA, Rotteveel JJ, et al. Sjögren-Larsson syndrome: clinical and MRI/MRS findings in FALDH-deficient patients. Neurology. 1999; 52:1345.
  3. Gordon N. Sjögren-Larsson syndrome. Dev Med Child Neurol. 2007; 49:152.
  4. Willemsen MA, Rotteveel JJ, van Domburg PH, et al. Preterm birth in Sjogren-Larsson syndrome. Neuropediatrics. 1999 Dec. 30(6):325-7.
  5. Rizzo WB, Craft DA. Sjögren-Larsson syndrome. Deficient activity of the fatty aldehyde dehydrogenase component of fatty alcohol:NAD+ oxidoreductase in cultured fibroblasts. J Clin Invest. 1991; 88:1643.
  6. Rizzo WB. Sjögren-Larsson syndrome. Semin Dermatol. 1993; 12:210.
  7. Willemsen MA, Van Der Graaf M, Van Der Knaap MS, et al. MR imaging and proton MR spectroscopic studies in Sjogren-Larsson syndrome: characterization of the leukoencephalopathy. AJNR Am J Neuroradiol. 2004 Apr. 25(4):649-57.
  8. Willemsen MA, Rotteveel JJ, de Jong JG, et al. Defective metabolism of leukotriene B4 in the Sjogren-Larsson syndrome. J Neurol Sci. 2001 Jan 15; 183(1):61-7
  9. McLennan JE, Gilles FH, Robb RM. Neuropathological correlation in Sjögren-Larsson syndrome. Oligophrenia, ichthyosis and spasticity. Brain. 1974; 97:693.
  10. Yamaguchi K, Handa T. Sjögren-Larsson syndrome: postmortem brain abnormalities. Pediatr Neurol. 1998; 18:338.

Ask Question

5000 Characters left Format the text using: # Heading, **bold**, _italic_. HTML code is not allowed.
By publishing this question you agree to the TOS and Privacy policy.
• Use a precise title for your question.
• Ask a specific question and provide age, sex, symptoms, type and duration of treatment.
• Respect your own and other people's privacy, never post full names or contact information.
• Inappropriate questions will be deleted.
• In urgent cases contact a physician, visit a hospital or call an emergency service!
Last updated: 2019-07-11 20:36