Microcephaly and simplified gyral pattern of the brain associated with early onset insulin-dependent diabetes mellitus.
Two families are presented with a child suffering from microcephaly with a simplified gyral pattern of the brain (SGP) and early onset insulin dependent diabetes mellitus (IDDM). The first patient was diagnosed postmortally with Wolcott-Rallison syndrome, after her younger brother developed IDDM, and a homozygous mutation in the eukaryotic translation initiation factor 2-alpha kinase 3 was found. The younger brother did not undergo magnetic resonance imaging (MRI). The patient from the second family has no EIF2AK3 mutation. SGP is considered to arise from decreased neuronal proliferation or increased apoptosis at an early stage of embryonal development, but insight into the pathways involved is minimal. EIF2AK3 is involved in translation initiation. It has been proposed that loss of function mutations reduce the ability of the cell to respond to endoplasmic reticulum stress, resulting in apoptosis of pancreatic Langerhans cells. Our findings suggest that in some cases, early onset IDDM and SGP can arise from common mechanisms leading to increased apoptosis.
de Wit
M C Y
MC
Department of Pediatric Neurology, Erasmus Medical Center Sophia Children's Hospital, Rotterdam, The Netherlands.
de Coo
I F M
IF
Julier
C
C
Delépine
M
M
Lequin
M H
MH
van de Laar
I
I
Sibbles
B J
BJ
Bruining
G J
GJ
Mancini
G M S
GM
D017668:Age of Onset; D002540:Cerebral Cortex / Q000002:abnormalities* / Q000473:pathology; D003922:Diabetes Mellitus, Type 1 / Q000150:complications*; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008279:Magnetic Resonance Imaging; D008297:Male; D008831:Microcephaly / Q000150:complications* / Q000473:pathology*; D010009:Osteochondrodysplasias / Q000000981:diagnostic imaging; D010024:Osteoporosis / Q000000981:diagnostic imaging; D011859:Radiography