© Kamla-Raj 2002 Int J Hum Genet, 2(4): 223-232 (2002) KEY WORDS Sjögren Larsson Syndrome; ALDH3A2; FALDH1; SLS ABSTRACT Sjögren Larsson syndrome (SLS) is a rare autosomal disorder that is characterised by congenital ichthyosis, spastic diplegia or qudriplegia and mental retardation. It is caused by the deficiency of the en- zyme, fatty aldehyde dehydrogenase (FALDH) that is required for the oxidation of fatty alcohol to fatty acid. The metabolism of leukotrine B4 (LTB4) has also been reported to be defective in SLS patients. The gene, ADLH3A2, encoding for FALDH has been localised at 17p11.2 and mutations in it cause SLS. The worldwide frequency of SLS is reported to be less than 1: 100,000 births but rarely a case has been reported from India. This article reviews the genetic factors in SLS and re- ports a case of SLS from India, with two similarly af- fected sibs. The management of SLS including genetic counselling and prenatal diagnostic possibilities are also discussed. INTRODUCTION Sjögren-Larsson Syndrome (SLS), sometimes called T. Sjögren syndrome to differentiate it from Sicca syndrome, is a rare neurocutaneous disorder that exhibits autosomal recessive inheritance. It is characterised by mental retardation, congenital ichthyosis, spastic diplegia or quadriplegia (Sjögren 1956; Sjögren and Larsson 1957). Mutations in the ADLH3A2 gene situated at 17p11.2 and encoding for fatty alcohol dehydrogenase (FALDH) are responsible for the causation of SLS. Worldwide the incidence of SLS is reported to be less than 1:100,000 births. However, its frequency amongst mentally retarded patients is observed as 1 in 1000 patients and 1 in 2500 amongst paediatric dermatology patients. Very high prevalence of SLS has been observed in north east of Sweden where an incident of 8.3:100,000 births has been reported (Jagell et al. 1981). However, there are no epidemiological reports on its frequency in the Indian population, and only rarely a case has been reported from here (Sood et al. 2002). The typical phenotype and clinical features of the SLS include congenital ichthysosis, lamellar-type hyperkeratosis, mental retardation, development delay, proportionate short stature, pigmentary abnormality of macula (Gilbert et al. 1968; Jagell et al. 1981), hypohidrotic or dry skin. However, symptoms like Dandy- Walker malformation (Fivenson et al. 1989), microcephaly, hypertelorism, juvenile macular dystrophy of retina (Willemsen et al. 2000a), enamel abnormalities, retinitis pigmentosa, chorioretinitis (Gilbert et al. 1968), widely spaced teeth, cataract, seizures, abnormal EEG, spasticity, and increased tendon reflex, have also been reported to be frequently associated with this syndrome (Winter and Baraitser 2000). Clinically ichthyosis is usually present at birth in patients with SLS, but in some it may be seen only after patients are one year old. There may be hyperkeratosis around the umbilicus, neck and the flexures. Mental retardation and spastic quadriplegia/diplegia are usually evident by the third year of life (Lacour 1996). Arms are usually less severely affected than the legs. About 20% of the cases show glistening spots on the macula (Theile 1974). The main biochemical defect underlying the SLS is the deficiency of the enzyme, fatty aldehyde dehydrogenase (FALDH), which is a component of the fatty alcohol:NAD oxidoreductase enzyme complex (FAO). The FALDH is a microsomal enzyme that is required Genetics of Sjögren Larsson Syndrome and a Case Report from India Arvind Rup Singh 1 , Jai Rup Singh 2 , Harshinder Kaur 3 , Gurpal Singh Sachdeva 4 , Anupam Kaur 2 and Amrita Darshan Singh 2 1. A-7, Guru Nanak Dev University Campus, Amritsar, India 2. Centre for Genetic Disorders, Guru Nanak Dev University, Amritsar, India 3. Department of Paediatrics, Govt Medical College, Patiala, India 4. Department of Medicine, Govt Medical College, Patiala, India Corresponding Author: Prof. Dr. Rup Singh, Coordina- tor, Centre for Genetic Disorders, Guru Nanak Dev University, Amritsar 143 005, India Phone: +91-183-258802 to 09 Extn. 3277 Fax: +91-183-258863, 258820, E-mail: jairup@vsnl.com & jairup@hotmail.com