title: Holoprosencephaly: an antenatally-diagnosed case series and subject review.
abstract: 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.
authors.affiliation: Cytogenetics Laboratory, Department of Pathology, Singapore General Hospital, Singapore. alvin.lim.s.t@sgh.com.sg
authors.forename: Alvin S T
authors.initials: AS
authors.lastname: Lim
authors.forename: Tse Hui
authors.initials: TH
authors.lastname: Lim
authors.forename: Su Keyau
authors.initials: SK
authors.lastname: Kee
authors.forename: Patrick
authors.initials: P
authors.lastname: Chia
authors.forename: Subramaniam
authors.initials: S
authors.lastname: Raman
authors.forename: Elizabeth L P
authors.initials: EL
authors.lastname: Eu
authors.forename: Jessie Y C
authors.initials: JY
authors.lastname: Lim
authors.forename: Sim Leng
authors.initials: SL
authors.lastname: Tien
mesh_terms: D000328:Adult; D002869:Chromosome Aberrations; D005260:Female; D016142:Holoprosencephaly / Q000175:diagnosis* / Q000235:genetics*; D006801:Humans; D007621:Karyotyping; D011247:Pregnancy; D011296:Prenatal Diagnosis; D014314:Trisomy