X-linked lissencephaly with absent corpus callosum and ambiguous genitalia.
Lissencephaly has been described in over 10 distinct malformation syndromes. Recently, we have recognized 5 children from four unrelated families with an almost identical disorder comprising lissencephaly with a posterior-to-anterior gradient and only moderate increase in thickness of the cortex, absent corpus callosum, neonatal-onset epilepsy, hypothalamic dysfunction including deficient temperature regulation, and ambiguous genitalia in genotypic males. Our observation of 5 affected males in one of these families is consistent with an X-linked pattern of inheritance. However, it differs in many regards from the X-linked form of isolated lissencephaly sequence that is associated with mutations of the XLIS (DCX) gene. Therefore, we propose that this disorder comprises a new X-linked malformation syndrome, which we refer to as X-linked lissencephaly with ambiguous genitalia (XLA-G).
Dobyns
W B
WB
Departments of Human Genetics, Neurology, and Pediatrics, The University of Chicago, Chicago, Illinois 60637, USA. wbd@genetics.uchicago.edu
Berry-Kravis
E
E
Havernick
N J
NJ
Holden
K R
KR
Viskochil
D
D
D061085:Agenesis of Corpus Callosum; D001921:Brain / Q000473:pathology; D002540:Cerebral Cortex / Q000002:abnormalities*; D002675:Child, Preschool; D004827:Epilepsy / Q000235:genetics; D005260:Female; D008040:Genetic Linkage; D005835:Genitalia / Q000002:abnormalities*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008279:Magnetic Resonance Imaging; D008297:Male; D010641:Phenotype; D013577:Syndrome; D014960:X Chromosome / Q000235:genetics*