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.
Muscular and Neurodegenerative Disease Unit, G. Gaslini Institute and University of Genova, Genova, Italy. roberta@biancheri.com
Roberta
R
Biancheri
Federico
F
Zara
Claudio
C
Bruno
Andrea
A
Rossi
Laura
L
Bordo
Elisabetta
E
Gazzerro
Federica
F
Sotgia
Marina
M
Pedemonte
Sara
S
Scapolan
Massimo
M
Bado
Graziella
G
Uziel
Marianna
M
Bugiani
Laura Doria
LD
Lamba
Valeria
V
Costa
Angelo
A
Schenone
Annemieke J M
AJ
Rozemuller
Paolo
P
Tortori-Donati
Michael P
MP
Lisanti
Marjo S
MS
van der Knaap
Carlo
C
Minetti
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