Phenotypic characterization of hypomyelination and congenital cataract.
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.


CONCLUSIONS
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.
Biancheri
Roberta
R
Muscular and Neurodegenerative Disease Unit, G. Gaslini Institute and University of Genova, Genova, Italy. roberta@biancheri.com
Zara
Federico
F
Bruno
Claudio
C
Rossi
Andrea
A
Bordo
Laura
L
Gazzerro
Elisabetta
E
Sotgia
Federica
F
Pedemonte
Marina
M
Scapolan
Sara
S
Bado
Massimo
M
Uziel
Graziella
G
Bugiani
Marianna
M
Lamba
Laura Doria
LD
Costa
Valeria
V
Schenone
Angelo
A
Rozemuller
Annemieke J M
AJ
Tortori-Donati
Paolo
P
Lisanti
Michael P
MP
van der Knaap
Marjo S
MS
Minetti
Carlo
C
D001706:Biopsy; D002386:Cataract / Q000150:complications / Q000151:congenital* / Q000235:genetics / Q000503:physiopathology*; D002524:Cerebellar Ataxia / Q000209:etiology; D003711:Demyelinating Diseases / Q000150:complications / Q000235:genetics / Q000503:physiopathology*; D005260:Female; D005808:Genes, Recessive; D020279:Hereditary Central Nervous System Demyelinating Diseases / Q000150:complications / Q000175:diagnosis / Q000235:genetics / Q000503:physiopathology*; D006801:Humans; D008607:Intellectual Disability / Q000209:etiology; D047908:Intracellular Signaling Peptides and Proteins / Q000172:deficiency; D008279:Magnetic Resonance Imaging; D008297:Male; D008565:Membrane Proteins / Q000172:deficiency; D009128:Muscle Spasticity / Q000209:etiology; D009420:Nervous System / Q000473:pathology / Q000503:physiopathology; D009431:Neural Conduction; D010523:Peripheral Nervous System Diseases / Q000150:complications / Q000235:genetics / Q000503:physiopathology*; D010641:Phenotype; D012189:Retrospective Studies; D016037:Single-Blind Method; D013497:Sural Nerve / Q000473:pathology
D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; C412048:HYCC1 protein, human