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HEREDITARY MONOGENIC DISEASES

           

Sjögren-Larsson syndrome

The Sjögren-Larsson syndrome is a neurocutaneous disease due to an inborn abnormality of lipid metabolism and characterized by congenital ichthyosis, intellectual deficit and spasticity. This syndrome is due to mutations ALDH3A2 gene (17p11.2) encoding fatty aldehyde dehydrogenase (FALDH), an enzyme required in the oxidation of fatty alcohols in fatty acid.

The prevalence is estimated at 1 / 250,000 and is highest in Sweden due to a founder effect.

Clinical features develop prenatally and during infancy. Patients are often born prematurely. At birth, there is often a slight hyperkeratosis that evolves into a generalized ichthyosis, more developed in the areas of flexion, neck, trunk and extremities. Unlike other forms of ichthyosis, pruritus is very frequent. It is also common at the time of birth erythroderma, which usually disappears with age. Neurological signs appear during the first or second year of life and result in psychomotor retardation, due to spastic diplegia or, much less commonly, in a spastic quadriplegia. Half of patients are unable to walk about. Seizures occur in 40% of cases. Intellectual deficit varies from moderate to severe, although there have been a few cases with normal intelligence. Dysarthria are common and delayed speech. Usually it is given an ophthalmologic involvement, characterized by crystalline inclusions of the retina around the fovea, photophobia and myopia are frequent. Dermatoglyphs abnormal described.

The syndrome is diagnosed by measuring the activity of FALDH or FAO in cultured fibroblasts obtained from skin biopsies. Diagnosis can be confirmed by a screening of known mutations using PCR specific allele, or by direct sequencing of the gene ALDH3A2.

In children not affected by spasticity, the differential diagnosis includes other forms of congenital ichthyosis, such as lamellar ichthyosis or congenital ichthyosiform erythroderma. Once neurologic symptoms appear, the differential diagnosis includes various neuro-ictiósicos, syndromes such as lipidosis with impaired storage of triglycerides (Chanarin-Dorfman syndrome), the mucosulfatidosis and Refsum disease.

Prenatal diagnosis is possible from biochemical or genetic in amniocytes or chorionic villus cells analysis.

Management involves the intervention of a multidisciplinary team of neurologists, dermatologists, ophthalmologists, orthopedic surgeons and physiotherapists.
Treating ichthyosis involves topical application of keratolytic or systemic retinoids administration. In general, seizures respond favorably to antiepileptic treatments and spasticity is relieved by surgery. Neurological symptoms and intellectual deficits do not evolve more after puberty.

Patients often live into adulthood but require lifelong care. Patients with early symptoms tend to be more severely affected.

GENE OR REGION STUDIED


  • ALDH3A2