Phenotypic characterization of hypomyelination and congenital cataract

• Published in: Annals of neurology 2007-08, Vol.62 (2), p.121-127
• Main Authors: Biancheri, Roberta, Zara, Federico, Bruno, Claudio, Rossi, Andrea, Bordo, Laura, Gazzerro, Elisabetta, Sotgia, Federica, Pedemonte, Marina, Scapolan, Sara, Bado, Massimo, Uziel, Graziella, Bugiani, Marianna, Lamba, Laura Doria, Costa, Valeria, Schenone, Angelo, Rozemuller, Annemieke J. M., Tortori-Donati, Paolo, Lisanti, Michael P., van der Knaap, Marjo S., Minetti, Carlo
• Format: Article
• Language: English
• Subjects: Biological and medical sciences; Biopsy; Cataract - complications; Cataract - congenital; Cataract - genetics; Cataract - physiopathology; Cerebellar Ataxia - etiology; Complex syndromes; Demyelinating Diseases - complications; Demyelinating Diseases - genetics; Demyelinating Diseases - physiopathology; Diseases of striated muscles. Neuromuscular diseases; Female; Genes, Recessive; Hereditary Central Nervous System Demyelinating Diseases - complications; Hereditary Central Nervous System Demyelinating Diseases - diagnosis; Hereditary Central Nervous System Demyelinating Diseases - genetics; Hereditary Central Nervous System Demyelinating Diseases - physiopathology; Humans; Intellectual Disability - etiology; Intracellular Signaling Peptides and Proteins - deficiency; Magnetic Resonance Imaging; Male; Medical genetics; Medical sciences; Membrane Proteins - deficiency; Muscle Spasticity - etiology; Nervous System - pathology; Nervous System - physiopathology; Neural Conduction; Neurology; Peripheral Nervous System Diseases - complications; Peripheral Nervous System Diseases - genetics; Peripheral Nervous System Diseases - physiopathology; Phenotype; Retrospective Studies; Single-Blind Method; Sural Nerve - pathology
• ISSN: 0364-5134; 1531-8249
• DOI: 10.1002/ana.21175

Objective To define the clinical and laboratory findings in a novel autosomal recessive white matter disorder called hypomyelination and congenital cataract, recently found to be caused by a deficiency of a membrane protein, hyccin, encoded by the DRCTNNB1A gene located on chromosome 7p21.3‐p15.3. Methods We performed neurological examination, neurophysiological, neuroimaging, and neuropathological studies on sural nerve biopsy in 10 hypomyelination and congenital cataract patients from 5 unrelated families. Results The clinical picture was characterized by bilateral congenital cataract, developmental delay, and slowly progressive neurological impairment with spasticity, cerebellar ataxia, and mild‐to‐moderate mental retardation. Neurophysiological studies showed a slightly to markedly slowed motor nerve conduction velocity in 9 of 10 patients, and multimodal evoked potentials indicated increased central conduction times. Neuroimaging studies demonstrated a diffuse supratentorial hypomyelination, with in some patients, additional areas of more prominent signal change in the frontal region. Sural nerve biopsy showed a slight‐to‐severe reduction in myelinated fiber density, with several axons surrounded by a thin myelin sheath or devoid of myelin. Interpretation Hypomyelination and congenital cataract is a novel autosomal recessive white matter disorder characterized by the unique association of congenital cataract and hypomyelination of the central and peripheral nervous system. Ann Neurol 2007