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  Table of Contents  
CASE REPORT
Year : 2014  |  Volume : 5  |  Issue : 2  |  Page : 185-188  

Sjögren-Larsson syndrome: A study of clinical symptoms in six children


1 Department of Pediatric Dermatology, Indira Gandhi Institute of Child Health, Bangalore, Karnataka, India
2 Department of Pediatric Neurology, Indira Gandhi Institute of Child Health, Bangalore, Karnataka, India

Date of Web Publication21-Apr-2014

Correspondence Address:
Sahana M Srinivas
Department of Pediatric Dermatology, Indira Gandhi Institute of Child Health, Bangalore, Karnataka
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/2229-5178.131099

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   Abstract 

Sjögren-Larsson syndrome (SLS) is a rare autosomal recessive disorder characterized by triad of congenital ichthyosis, spastic paresis, and mental retardation. It is an inborn error of lipid metabolism caused by deficiency of the enzyme fatty aldehyde dehydrogenase. We report our observations of six children with SLS.

Keywords: Congenital ichthyosis, mental retardation, spastic paresis


How to cite this article:
Srinivas SM, Raju KV, Hiremagalore R. Sjögren-Larsson syndrome: A study of clinical symptoms in six children. Indian Dermatol Online J 2014;5:185-8

How to cite this URL:
Srinivas SM, Raju KV, Hiremagalore R. Sjögren-Larsson syndrome: A study of clinical symptoms in six children. Indian Dermatol Online J [serial online] 2014 [cited 2019 Dec 13];5:185-8. Available from: http://www.idoj.in/text.asp?2014/5/2/185/131099


   Introduction Top


Sjögren-Larsson syndrome (SLS) is an autosomal recessive neurocutaneous disorder characterized by clinical triad of congenital ichthyosis, diplegia or tetraplegia, and learning disability/mental retardation. [1] SLS is caused by mutation in the gene for fatty aldehyde dehydrogenase (FALDH) which catalyzes oxidation of long chain aliphatic alcohols to corresponding fatty acids. This leads to accumulation of aldehyde-modified lipids or fatty alcohol which probably disrupts the barrier function of skin and white matter of brain. [2] We describe a series of six children with SLS seen over a period of 1 year to highlight their varied clinical presentation.


   Case Report Top


The study comprised six children, ranging from 1 to 12 years with an equal gender ratio diagnosed as SLS seen during the period January 2012 to December 2012, referred from pediatric neurology department. The clinical summary of patients is described in [Table 1]. Four children were born of consanguineous marriage. Five children were born prematurely. History of collodion membrane was present in one child. All the children had ichthyosis since birth and were associated with delayed milestones and speech abnormalities [Table 1]. There was generalized ichthyosis in all patients with relative sparing of face [Figure 1]. Type of scales varied from fine [Figure 2] and [Figure 3] to lamellar type [Figure 4] and [Figure 5]. Pruritus was present only in two children. Five children had seizures and were on anticonvulsants. Spastic diplegia was present in four cases and two children had spastic quadriplegia [Figure 6]. One child (case 1) had cardiomegaly with congenital heart disease. One child had nystagmus. None of our children had any other ocular findings. Skin biopsy was done in all children; features showed hyperkeratosis, parakeratosis, and normal to thinned out granular layer with mild perivascular lymphocytic infiltrate in dermis consistent with ichthyosis [Figure 7]. Brain magnetic resonance imaging (MRI) in all children revealed delayed myelination with signal changes in periventricular region predominantly involving occipital region [Figure 8].
Table 1: Clinical summary of patients

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Figure 1: Case 1-Fine scaling over extremities with sparing of face in a 1.5-year-old female child

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Figure 2: Case 2-X-linked type of ichthyosis over extremities

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Figure 3: Case 3-Fine scaling over extremities similar to ichthyosis vulgaris

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Figure 4: Case 4-Three-year-old male child with lamellar type of scales over the extremities

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Figure 5: Case 5-Lamellar type of scaling over extremities

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Figure 6: Case 6-Generalized ichthyosis (lamellar type scales) with spastic quadriplegia

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Figure 7: Epidermis shows hyperkeratosis, parakeratosis, thinned out granular layer with mild perivascular lymphocytic infiltrate in dermis (H and E, ×40)

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Figure 8: T2-weighted magnetic resonance imaging (MRI) showing signal changes in bilateral peritrigonal regions

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   Discussion Top


In 1957, Sjögren and Larsson described the disorder affecting 28 patients from a highly consanguineous population in a remote area of Sweden with clinical triad of mental retardation, spastic diplegia, and congenital ichthyosis. [1] The incidence of SLS is 1 in 200,000 births in Sweden, but it occurs more rarely worldwide. SLS is caused due to recessive mutations in the fatty aldehyde dehydrogenase (FALDH) gene FALDH3A2 on the short arm of chromosome 17p11. [2] More than 72 mutations in FALDH3A2 are known in SLS patients. [3]

The disorder presents at birth or in the neonatal period with varying degrees of erythema and ichthyosis, but a collodion membrane is rarely seen. Infants with SLS tend to be born prematurely. Although erythema may be present at birth, it is usually not evident after a year of age. Persistent pruritus is common. The morphology of the scaling may be fine, dandruff-like similar to ichthyosis vulgaris or X-linked recessive ichthyosis or lamellar similar to autosomal recessive congenital ichthyosis. [4] The ichthyosis is generalized, but sites more predominantly affected are lower abdomen, sides and nape of neck, and flexures. A distinctive sign is periumbilical hyperkeratosis with radiating furrows. [5] Palmoplantar keratoderma is seen in 50% of cases. The diagnosis of SLS is delayed until the onset of neurological symptoms, because only cutaneous manifestations are present at birth.

The neurological symptoms appear in the first or second year of life. Speech and motor delays are the common initial signs. Spasticity appears before 3 years of age and is more severe in lower limbs. Seizures are present in one-third of patients. There is no progression of neurological findings or mental retardation after puberty. [6] Neuroimaging studies of the cerebral white matter and corticospinal tracts shows white matter disease, delayed myelination, periventricular gliosis, and a permanent myelin deficit. [7] One-third of patients present with perifoveal glistening dots in the ocular fundus which appear after several years of age. [8] None of the children in our cohort had retinal changes. Long-term follow-up is necessary to document retinal changes.

The histopathological features are nonspecific and include hyperkeratosis and acanthosis with a normal granular layer. The diagnosis of SLS can be confirmed by measurement of enzyme activity in cultured skin fibroblasts or leucocytes. Sequence analysis of FALDH3A2 gene causing mutations is highly sensitive and also detects possible carrier. [9]

There is no permanent cure for SLS and no specific therapy. Multidisciplinary approach includes team of dermatologist, neurologist, ophthalmologist, orthopaedician, and physiotherapist. Topical emollients, keratolytics, calcipotriol, and oral retinoids can be used to improve the cutaneous symptoms. [10] All our patients were managed symptomatically with topical emollients and keratolytics. Cutaneous symptoms improved after treatment.

In our case series, one child had congenital heart disease and cardiomegaly that has not been described in earlier reports. Due to the limited availability of diagnostic laboratories, enzyme analysis was not done in our study. High index of suspicion is necessary for the diagnosis of SLS. Any case of congenital ichthyosis with spastic paresis and mental retardation should be evaluated for SLS.

 
   References Top

1.Sjogren T, Larsson T. Oligophrenia in combination with congenital ichthyosis and spastic disorder; a clinical and genetic study. Acta Psychiatr Neurol Scand Suppl 1957;113:1-112.  Back to cited text no. 1
[PUBMED]    
2.De Laurenzi V, Rogers GR, Hamrock DJ, Marekov LN, Steinert PM, Compton JG, et al. Sjögren-Larsson syndrome is caused by mutations in the fatty aldehyde dehydrogenase gene. Nat Genet 1996;12:52-7.  Back to cited text no. 2
    
3.Rizzo WB. Sjogren-Larsson syndrome: Molecular genetics and biochemical pathogenesis of fatty aldehyde dehydrogenase deficiency. Mol Genet Metab 2007;90:1-9.  Back to cited text no. 3
[PUBMED]    
4.Jagell S, Lidén S. Ichthyosis in the Sjögren-Larsson syndrome. Clin Genet 1982;21:243-52.  Back to cited text no. 4
    
5.Lacour M. Update on Sjögren-Larsson syndrome. Dermatology 1996;193:77-82.  Back to cited text no. 5
[PUBMED]    
6.Verhoog J, Fuijkschot J, Willemsen M, Ketelaar M, Rotteveel J, Gorter JW. Sjögren-Larsson syndrome: Motor performance and everyday functioning in 17 patients. Dev Med Child Neurol 2008;50:38-43.  Back to cited text no. 6
    
7.Nakayama M, Távora DG, Alvim TC, Araújo AC, Gama RL. MRI and 1H-MRS findings of three patients with Sjögren-Larsson syndrome. Arq Neuropsiquiatr 2006;64 (2B):398-401.  Back to cited text no. 7
    
8.Willemsen MA, Cruysberg JR, Rotteveel JJ, Aandekerk AL, Van Domburg PH, Deutman AF. Juvenile macular dystrophy associated with deficient activity of fatty aldehyde dehydrogenase in Sjögren-Larsson syndrome. Am J Ophthalmol 2000;130:782-9.  Back to cited text no. 8
    
9.Gordon N. Sjogren-Larsson syndrome. Dev Med Child Neurol 2007;49:152-4.  Back to cited text no. 9
[PUBMED]    
10.Gånemo A, Jagell S, Vahlquist A. Sjögren-Larsson syndrome: A study of clinical symptoms and dermatological treatment in 34 Swedish patients. Acta Derm Venereol 2009;89:68-73.  Back to cited text no. 10
    


    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6], [Figure 7], [Figure 8]
 
 
    Tables

  [Table 1]


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