Sjögren-larsson syndromeQ87.13

Autosomal recessive, rare, syndromal ichthyosis with combination of oligophrenia, ichthyosis, central coordination disorder usually in the form of spastic di-, rarely tetraplegia.

Autosomal recessive mutations of the ALDH3A2 gene(aldehyde dehydrogenase 3 A2 gene; gene locus: 17p11.2) with consecutive reduction in the activity of the fatty alcohol NAD+ oxidoreductase complex (FALDH), in particular dehydrogenase. By converting fatty aldehydes into fatty acids, FALDH prevents the accumulation of toxic fatty aldehydes. Due to the reduced enzyme activity, the mutation leads to the accumulation of aldehyde-modified lipids or fatty alcohols, which can impair skin and brain function. Furthermore, the toxicity of long-chain aldehydes in FALDH-deficient cells appears to lead to hyperproliferation of keratinocytes (ichthyosis) (Xu YC et al. 2020).

Skin changes corresponding to ichthyosis congenita, hypohidrosis and di- or tetraplegia manifesting in the first year of life, short stature, oligophrenia, skeletal, dental and retinal changes may occur.

Variable clinic with oligophrenia, generalized ichthyosis (up to the development of erythroderma), possibly also hyperpigmentation, progressive cerebral tone and movement disorders (diplegia, tetraplegia) and speech disorders. In individual cases, ocular fundus abnormalities, in particular retinitis pigmentosa and macular degeneration as well as glistening spots.

Other associations include thoracic kyphosis, epilepsy or oligoepilepsy, gingivitis and periodontitis, tooth enamel defects, degenerative stigmata such as hypertelorism or epicanthus.

Clinical presentation with syndromal symptoms; molecular genetic diagnosis with wet detection of the mutation.

1. Akdeniz N et al. (2003) Report of a Turkish child with Sjoren-Larsson syndrome associated with peripheral nerve involvement. J Dermatol 30: 222-225
2. Blanchet-Bardon CB et al. (1991) Acitretin in the treatment of severe disorders of keratinization. J Am Acad Dermatol 24: 982-86
3. DiGiovanna JJ et al (2003) Ichthyosis: etiology, diagnosis, and management. Am J Clin Dermatol 4: 81-95
4. Kelson TL et al. (1992) Carrier detection for Sjögren-Larsson syndrome: J Inherit Metab Dis 15(1): 105-111
5. Mohrenschlager M et al (2000) Sjogren-Larsson syndrome. Dermatology 51: 250-255
6. Scalais E et al. (1992) Sjögren-Larsson-like syndrome with bone dysplasia and normal fatty alcohol N-oxidoreductase activity. Pediatr Neurol 8: 459-465
7. Sjögren T, Larsson T (1957) Oligophrenia in combination with congenital ichthyosis and spastic disorders. A clinical and genetic study. Acta psychiat neurol scand 32(Suppl113): 9-105
8. Tabsh K et al. (1993) Sjögren-Larsson syndrome: technique and timing of prenatal diagnosis. Obstet Gynecol 82 (Suppl): 700-703
9. Theile U (1974) Sjögren-Larsson syndrome. Oligophrenia-Ichthyosis-Di-/Tetraplegia. Human Genetics 22: 91-118

10. Xu YC et al (2020) Sjogren-Larsson syndrome associated hypermelanosis. J Cosmet Dermatol 19:789-798.