Case Report Heterogeneity of Marinesco-Sjögren Syndrome: Report of Two Cases Uluç Yis ¸ MD a, * , Sebahattin Cirak MD b , Semra Hız MD c , Handan Çakmakçı MD d , Eray Dirik MD c a Department of Pediatric Neurology, Gaziantep Children’s Hospital, Gaziantep, Turkey b Dubowitz Neuromuscular Centre, University College London Institute of Child Health, London, United Kingdom c Department of Pediatric Neurology, School of Medicine, Dokuz Eylul University, _ Izmir, Turkey d Department of Radiology, School of Medicine, Dokuz Eylul University, _ Izmir, Turkey article information Article history: Received 26 February 2011 Accepted 29 August 2011 abstract Marinesco-Sjögren syndrome is an autosomal recessive, multiorgan disorder with cardinal features of cerebellar ataxia, congenital or early childhood cataracts, psychomotor retardation, myopathy, and short stature. Mutations in the SIL1 gene on chromosome 5q31 were demonstrated to cause Marinesco-Sjögren syndrome. We describe two Turkish patients with clinical characteristics of Marinesco-Sjögren syndrome, but without mutations in SIL1 . These two patients also manifested cerebral white matter involvement in cranial imaging, which was previously described in Marinesco-Sjögren syndrome. Marinesco-Sjögren syndrome is genetically heterogeneous, and mutations of SIL1 are often not evident. Consequently, we presume that new genes for Marinesco-Sjögren syndrome await discovery. New genes hold the promise of furthering the mechanistic understanding of the condition, enabling clinically meaningful genetic classification schemes to be designed. Ó 2011 Elsevier Inc. All rights reserved. Introduction Marinesco-Sjögren syndrome is an autosomal recessive disorder first described by Marinesco et al. in a Romanian family [1]. Cerebellar ataxia, bilateral cataracts, mild to moderate mental retardation, short stature, hypergonadotropic hypogonadism, and skeletal abnormali- ties comprise the cardinal features of the disease [1]. Mutations in the SIL1 gene on chromosome 5q31 were demonstrated to cause Marinesco-Sjögren syndrome, but are often not evident [2,3]. Cere- bellar atrophy, especially of the vermis, is considered an important neuroradiologic finding in Marinesco-Sjögren syndrome, but it is not a universal feature [4,5]. The diagnosis in this genetically and clinically heterogeneous disorder ultimately rests on the clinical phenotype. We present two patients with congenital cataracts, cerebellar ataxia, and neuroradiologic features consistent with the clinical phenotype of Marinesco-Sjögren syndrome, but who did not manifest mutations in SIL1 . Case Report Patient 1 This 6-year-old girl is the fourth child of consanguineous parents. She was born at term after an uneventful pregnancy. Bilateral cataracts were observed on routine examination at age 3 months, and were surgically treated at age 4 months. She began to walk late (independently at 2.5 years old). Gait ataxia was observed by her parents at age 3 years. Her development of receptive language abilities and social interaction skills is poor relative to that of her siblings. She is currently able to say a limited number of words, and a physical examination revealed short stature (104 cm; 5th percentile) but normal body weight and head circumference, with no dysmorphic features. Positive cerebellar signs included gait ataxia, dysmetria, and dysdiadochokinesis. Her deep tendon reflexes were hyperactive, with mild spasticity in the legs. Her level of serum creatine kinase was 500 IU/L, and electromyography revealed myopathic changes in all tested muscle groups. Metabolic investigations, including serum and urine amino acids, urine organic acids, serum lactate, pyruvate, and ammonia, indicated no abnormalities. Cranial magnetic resonance imaging at age 4 years revealed cerebellar atrophy, which was more prominent in the cerebellar vermis. A gliotic focus was evident in the right periventricular white matter, along with lateral ventricular enlargement (Fig 1a-c). The patient’s signs and findings have not been progressive so far. Patient 2 This 4-year-old boy is the second child of nonconsanguineous parents. He was born at term after an uneventful pregnancy. Congenital cataracts were evident immediately after birth because of his lack of the “red reflex,” and were extracted at age 3 months. He exhibited a global delay of development from infancy. Head control was achieved at age 6 months, unsupported sitting at age 12 months, and independent walking at age 2 years. Gait ataxia was present from that time. The ataxia has not been progressive. At age 4 years, he manifested three generalized seizures, which responded well to treatment with phenobarbital. A physical examination revealed short stature (92 cm; 5th percentile), but normal body weight and head circumference, without dysmorphic features. Gait ataxia and intention tremor were present. His deep tendon reflexes were hyperac- tive, with mild spasticity in the legs. * Communications should be addressed to: Dr. Yis ¸ ; Department of Pediatric Neurology; Gaziantep Children’s Hospital; Gaziantep, Turkey 27000. E-mail address: ulyis@yahoo.com Contents lists available at ScienceDirect Pediatric Neurology journal homepage: www.elsevier.com/locate/pnu 0887-8994/$ - see front matter Ó 2011 Elsevier Inc. All rights reserved. doi:10.1016/j.pediatrneurol.2011.08.015 Pediatric Neurology 45 (2011) 409e411