Cases of holoprosencephaly which occurred in the west of Scotland over
the past 20 years were ascertained from genetics, paediatric, and pat
hology department records. Fifty cases were identified of which 17 had
an underlying cytogenetic abnormality. Of the remaining 33 cases, 26
were delivered after 28 weeks' gestation giving a birth prevalence of
1 in 26 730. Twenty-one babies were liveborn and nine children are cur
rently alive. All survivors are profoundly mentally retarded and most
have seizures. Twenty-eight patients with non-chromosomal holoprosence
phaly had a total of 23 sibs and three families were identified where
there was either recurrence of holoprosencephaly (one family), a relat
ed cerebral malformation (one family), or mental handicap (one family)
giving an overall recurrence risk for serious neurological disability
of 12% (standard error 7%). We conclude that holoprosencephaly does n
ot necessarily breed true and this observation should be taken into ac
count when giving genetic counselling and attempting ultrasound prenat
al diagnosis after the birth of an affected child.