Holoprosencephaly, sacral anomalies, and situs ambiguus in an infant with partial monosomy 7q/trisomy 2p and SHH and HLXB9 haploinsufficiency

We report an infant with holoprosencephaly (HPE), sacral anomalies, and sit us ambiguus with a 46,XY,der(7)t(2;7)(p23.2;q36.1) karyotype as a result of an adjacent-1 segregation of a t(2;7)pat. The chromosomal abnormality was diagnosed prenatally after sonographic detection of HPE in the fetus. The b aby was born at 37 weeks gestation, and died in the newborn period; he had dysmorphic features consistent with HPE sequence. Postmortem internal evalu ation showed semilobar MPE, abdominal situs ambiguus, multiple segments of bowel atresia, dilatation of the ureters, and bony sacral anomalies. Molecu lar analysis confirmed hemizygosity for the SHH and HLXB9 genes, which are likely to be responsible for the HPE and sacral phenotypes. respectively. I mmunohistochemical studies showed intact dopaminergic pathways in the mesen cephalon, suggesting that midbrain dopamine neuron induction appears to req uire only one functioning SHH allele.