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Phenotypic characterization of hypomyelination and congenital cataract
Author(s) -
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,
Sche Angelo,
Rozemuller Annemieke J. M.,
TortoriDonati Paolo,
Lisanti Michael P.,
van der Knaap Marjo S.,
Minetti Carlo
Publication year - 2007
Publication title -
annals of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.764
H-Index - 296
eISSN - 1531-8249
pISSN - 0364-5134
DOI - 10.1002/ana.21175
Subject(s) - white matter , ataxia , pathology , medicine , myelin , spasticity , neuroimaging , optic nerve , neuroscience , central nervous system , anatomy , psychology , magnetic resonance imaging , anesthesia , radiology
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