Chromosome 1p32-p31 deletion syndrome: prenatal diagnosis by array comparative genomic hybridization using uncultured amniocytes and association with NFIA haploinsufficiency, ventriculomegaly, corpus callosum hypogenesis, abnormal external genitalia, and intrauterine growth restriction.
OBJECTIVE
To present prenatal diagnosis of chromosome 1p32-p31 deletion syndrome with NFIA haploinsufficiency, ventriculomegaly, corpus callosum hypogenesis, abnormal external genitalia, and intrauterine growth restriction and to review the literature.


RESULTS
A 26-year-old, primigravid woman was referred for amniocentesis at 30 weeks of gestation because of hydrocephalus and short limbs. Prenatal ultrasound showed macrocephaly, prominent forehead, ventriculomegaly, corpus callosum hypogenesis, micrognathia, and ambiguous external genitalia. Amniocentesis was performed, and array comparative genomic hybridization using uncultured amniocytes revealed a 22.2-Mb deletion of 1p32.3-p31.1 [arr cgh 1p32.3p31.1 (55,500,291 bp-77,711,982 bp)×1] encompassing the genes of NFIA, GPR177, and 89 additional genes. Cytogenetic analysis revealed a karyotype of 46,XX,del(1)(p31.1p32.3)dn. At 33 weeks of gestation, a dead fetus was delivered with a body weight of 1536g (<5(th) centile); relative macrocephaly; a broad face; prominent forehead; hypertelorism; anteverted nostrils; micrognathia; low-set ears; and abnormal female external genitalia with labial fusion, labial hypertrophy, absence of vaginal opening, and clitoral hypertrophy. Polymorphic DNA marker analysis determined a paternal origin of the deletion.


CONCLUSIONS
Prenatal diagnosis of ventriculomegaly with an abnormal corpus callosum should alert subtle chromosome aberrations and prompt molecular cytogenetic investigation if necessary. Fetuses with chromosome 1p32-p31 deletion syndrome and haploinsufficiency of the NFIA gene may present ventriculomegaly, corpus callosum hypogenesis, abnormal external genitalia, and intrauterine growth restriction in the third trimester.
Department of Obstetrics and Gynecology, Mackay Memorial Hospital, Taipei, Taiwan. cpc_mmh@yahoo.com
Chih-Ping
CP
Chen
Yi-Ning
YN
Su
Yi-Yung
YY
Chen
Schu-Rern
SR
Chern
Yu-Peng
YP
Liu
Pei-Chen
PC
Wu
Chen-Chi
CC
Lee
Yu-Ting
YT
Chen
Wayseen
W
Wang
D000015:Abnormalities, Multiple / Q000175:diagnosis* / Q000235:genetics*; D000328:Adult; D061085:Agenesis of Corpus Callosum / Q000175:diagnosis / Q000235:genetics; D000649:Amniocentesis / Q000379:methods; D002872:Chromosome Deletion; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics*; D055028:Comparative Genomic Hybridization; D012734:Disorders of Sex Development / Q000175:diagnosis / Q000235:genetics; D005260:Female; D005317:Fetal Growth Retardation / Q000175:diagnosis / Q000235:genetics; D005836:Genitalia, Female / Q000002:abnormalities; D057895:Haploinsufficiency / Q000235:genetics; D006801:Humans; D006849:Hydrocephalus / Q000175:diagnosis / Q000235:genetics; D051839:NFI Transcription Factors / Q000235:genetics*; D011247:Pregnancy; D011296:Prenatal Diagnosis
D051839:NFI Transcription Factors; C497592:NFIA protein, human