CASE REPORT Sjo ¨gren–Larsson syndrome: phenotypic variability in two brothers with a neurocutaneous disorder Luciana Losito • Leonarda Gennaro • Marta De Rinaldis • Marilena Cacudi • Antonio Trabacca Received: 24 December 2011 / Accepted: 14 January 2012 / Published online: 2 February 2012 Ó Belgian Neurological Society 2012 Abstract Sjo ¨gren–Larsson syndrome (SLS) is a rare autosomal recessively inherited neurocutaneous disorder caused by mutations in the ALDH3A2 gene that encodes fatty aldehyde dehydrogenase, an enzyme that catalyzes the oxidation of fatty aldehyde to fatty acid. It is charac- terized by an unusual combination of cutaneous and neu- rologic signs and symptoms. The authors describe two brothers of consanguineous parents with SLS, one of whom was born from a dizygotic twin pregnancy (with an apparently normal sister), and they focus on the variability of the clinical findings of the syndrome even among sib- lings and twins. Keywords Sjo ¨gren–Larsson syndrome Á Neurocutaneous disorder Á Ichthyosis Introduction Sjo ¨gren–Larsson syndrome (SLS; MIM #270200) is a rare autosomal recessively inherited neurocutaneous disorder caused by mutations in the ALDH3A2 gene that encodes fatty aldehyde dehydrogenase, an enzyme that catalyzes the oxidation of fatty aldehyde to fatty acid. It is charac- terized by an unusual combination of symptoms including congenital ichthyosis, mental retardation, and spastic diplegia or tetraplegia [1]. The pathogenesis of the cutaneous and neurologic symptoms is thought to result from abnormal lipid accumulation in the membranes of skin and brain [2]. Patients with SLS also accumulate leukotriene B4 and its omega-hydroxy metabolite, which are probably responsible for pruritus [3]. More than 70 mutations in ALDH3A2 have been discovered in patients with SLS, including amino acid substitutions, deletions, insertions, and splicing errors [4]. Its prevalence has been estimated to be 0.4/100.000 individuals [5]. This paper reports on two brothers of consanguineous parents with SLS, one of whom born from a dizygotic twin pregnancy (with a normal sister). Case study The family pedigree is shown in Fig. 1. Patient 1 is a 18-year-old boy with spastic quadriplegia. He is the first child of healthy consanguineous parents (first cousins); the father is 55 years old, the mother is 48 years old. Family history was unremarkable. Maternal pregnancy history were unremarkable but the mother had five miscarriages. Patient 1 was delivered with labor dystocia at 37 weeks of gestation and he received orotracheal intubation for 2 weeks. His motor development was severely delayed: the severity of his motor disability was assessed to be at level 5 of the gross motor function classification system (GMFCS) [6]. A psychological examination showed profound intel- lectual disability and delayed speech development. Fur- thermore, this patient presented with short stature, moderate kyphoscoliosis and lamellar ichthyosis on the abdomen (Fig. 2a), back (Fig. 2b) and, in particular, on the extensor surfaces of both legs. He also had pruritus and had been taking an antihistaminic drug. Brain magnetic reso- nance imaging (bMRI) showed agenesis of corpus L. Losito Á L. Gennaro Á M. De Rinaldis Á M. Cacudi Á A. Trabacca (&) Scientific Institute I.R.C.C.S. ‘‘Eugenio Medea’’, ‘‘La Nostra Famiglia’’, Unit of Neurorehabilitation I (Developmental Neurology and Functional Rehabilitation), Brindisi Research Centre, Piazza ‘‘A. Di Summa’’, 72100 Brindisi, Italy e-mail: antonio.trabacca@os.lnf.it 123 Acta Neurol Belg (2012) 112:205–208 DOI 10.1007/s13760-012-0035-z