Caudal regression and holoprosencephaly in a fetus of a diabetic mother

Abstract

It is well established that the risk of malformations in children born to women with overt diabetes is two to three times greater than the general population. Caudal regression (combining sacral agenesis and hypoplastic femurs) is a rare usually sporadic disorder that is most commonly associated with maternal diabetes. Holoprosencephaly is the abnormal formation and separation of the developing brain and is also known to be associated with maternal diabetes. Both anomalies have been mapped to 7q36 (Huggins, 1998, Strachan, 1998).

Case report: We describe a fetus with caudal regression and holoprosencephaly in a 30-year-old diabetic woman who was well controlled on insulin therapy. Ultrasound examination at 31.8 weeks revealed multiple anomalies including holoprosencephaly, hypotelorism, an abnormal nasal structure suggestive of a single nostril, abnormal sacrum, undetectable femurs, severe clubbing of the feet which appeared rocker-bottom, clinodactyly and clenched fingers. The 2150 g male fetus was stillborn at 34 weeks. Post-mortem examination revealed cardiomegaly and an absent left kidney, and confirmed the ultrasound findings of craniofacial and skeletal anomalies. Chromosome analysis on the tissue culture revealed a normal 46,XY male complement in all cells analyzed.

Conclusion: Although diabetic embryopathy cannot be excluded as the causative factor for these malformations, the presence of two rare anomalies which map to the same chromosome region is suggestive of a specific genetic defect. The human Sonic Hedgehog gene (SHH), which maps to 7q36, has recently been reported to be expressed not only in the CNS but also in human limb buds (Odent, 98). The possibility that an alteration in the SHH gene may be the cause of this combination of anomalies in this fetus is currently under investigation.