Sjogren-Larsson syndrome
This autosomal recessive syndrome combines icthyosis with mental retardation and spastic paralysis. Sjogren & Larsson (1957) estimated its incidence as one in 10 000 births in the area of northern Sweden in which their 28 cases were found. These 28 patients comprised 14 pairs of siblings and the consanguinity rate in their families was high.
The cutaneous hallmark is icthyosis, usually from birth, and the child may present as a 'Collodion' baby. Hyperkeratosis and scaling of the skin are widespread over the trunk and limbs and involves the hands and feet. Facial lesions are usually mild. The skin is thick and patterned like leather, often with a 'fish-scale' appearance.
The neurological features are mental retardation, which seems invariable and is often severe, and spastic diplegia with symmetrical involvement of both sides, more marked in the legs than the arms. In about 75% of reported cases, walking has been impossible without support and many patients are chair- or bed-bound. Seizures of various kinds are common. Pigmentary degeneration in the macular region occurs in about 25% of patients.
A review of all 35 Sjogren-Larsson syndrome patients in Sweden alive in 1978 (Jagell & Heijbel 1982), showed that 32 had pronounced or severe spastic diplegia and two had severe tetraplegia. The most motor handicapped were also the most mentally handicapped, but the degree of icthyosis and ocular fundal changes varied independently of the cerebral symptoms. CT showed no morphological abnormalities of the brain. Signs of spasticity and mental retardation present before the age of 3 years were clinical confirmation of the diagnosis.
The main neuropathological features noted in the few autopsied cases are degeneration and loss of neurons in the cortex and basal ganglia, demyelination in cerebral white matter, corticospinal and vestibulospinal tracts and Pur- kinje cell loss with focal atrophy in the cerebellum (McLennan et al 1974).
Recent reports have shown that a proportion of these patients have an abnormality of fatty alcohol metabolism with a defect of fatty alcohol oxidoreductase in cultured fibroblasts and leucocytes (Rizzo et al 1988) as well as in the skin (Lake et al 1989, Harper et al 1994) (Fig. 21.19).
Fetal skin biopsy has proved reliable and safe for prenatal diagnosis.
The case of a 19-year-old woman with icthyosis, mental retardation and mild spasticity, with normal fatty acid metabolism, was reported by Koone et al (1990). Ultrastructural studies of her skin showed abnormal epidermal lamellar bodies, not unlike those seen in neutral lipid storage disease, and the authors suggest that she has a new neurocutaneous syndrome secondary to abnormal lipid metabolism.
