Holoprosencephaly: an antenatally-diagnosed case series and subject review.
BACKGROUND
Holoprosencephaly (HPE) is an uncommon congenital failure of forebrain development. Although the aetiology is heterogeneous, chromosomal abnormalities or a monogenic defect are the major causes, accounting for about 40% to 50% of HPE cases. At least 7 genes have been positively implicated, including SHH, ZIC2, SIX3, TGIF, PTCH1, GLI2, and TDGF1.


METHODS
Twelve antenatally- and 1 postnatally-diagnosed cases are presented in this study. These comprised 6 amniotic fluid, 3 chorionic villus, 2 fetal blood, 1 peripheral blood, and 1 product of conception.


RESULTS
The total chromosome abnormality rate was 92.3%, comprising predominantly trisomy 13 (66.7%). There was 1 case of trisomy 18, and 3 cases of structural abnormalities, including del13q, del18p, and add4q.


CONCLUSIONS
Despite the poor outcome of an antenatally-diagnosed HPE and the likely decision by parents to opt for a termination of pregnancy, karyotyping and/or genetic studies should be performed to determine if a specific familial genetic or chromosomal abnormality is the cause. At the very least, a detailed chromosome analysis should be carried out on the affected individual. If the result of high resolution karyotyping is normal, Fluorescence in situ hybridisation (FISH) and/or syndrome-specific testing or isolated holoprosencephaly genetic testing may be performed. This information can be useful in making a prognosis and predicting the risk of recurrence.
Lim
Alvin S T
AS
Cytogenetics Laboratory, Department of Pathology, Singapore General Hospital, Singapore. alvin.lim.s.t@sgh.com.sg
Lim
Tse Hui
TH
Kee
Su Keyau
SK
Chia
Patrick
P
Raman
Subramaniam
S
Eu
Elizabeth L P
EL
Lim
Jessie Y C
JY
Tien
Sim Leng
SL
D000328:Adult; D002869:Chromosome Aberrations; D005260:Female; D016142:Holoprosencephaly / Q000175:diagnosis* / Q000235:genetics*; D006801:Humans; D007621:Karyotyping; D011247:Pregnancy; D011296:Prenatal Diagnosis; D014314:Trisomy