A gene for autosomal dominant sacral agenesis maps to the holoprosencephaly region at 7q36

Sacral agenesis is a rare disorder of uncertain incidence that has been reported in diverse populations. Although usually sporadic and most commonly associated with maternal diabetes, there is a hereditary form which may occur in isolation or with a presacral mass (anterior meningocele and/or presacral teratoma) and anorectal abnormalities, which constitute the Currarino triad (MIM 176450). The radiological hallmark of hereditary sacral agenesis is a hemi-sacrum (sickle-shaped sacrum) with intact first sacral vertebra. Bowel obstruction is the usual neonatal presentation, but, unlike other neural tube defects, adult presentation is not uncommon. The major pathology is confined to the pelvic cavity and may present as a space-occupying lesion or meningitis due to ascending infection. All recurrences in families have been compatible with autosomal dominant inheritance except for those associated with the isomerism gene at Xq24-q27.1 (ref. 3). Several associated cytogenetic defects have been reported, including 7q deletions. Previous studies failed to detect linkage to HLA markers, but we now present evidence for a location on 7q36. The same region also contains a gene for holoprosencephaly, an early malformation of the extreme rostral end of the neural tube.