Fetal holoprosencephaly: associated malformations and chromosomal defects

Area of Science:

• Medical Genetics
• Developmental Biology
• Prenatal Diagnosis

Background:

• Holoprosencephaly (HPE) is a congenital disorder resulting from incomplete separation of the forebrain.
• Genetic factors play a significant role in the etiology of HPE.
• Accurate genetic diagnosis is essential for prognosis and genetic counseling.

Purpose of the Study:

• To investigate the frequency of chromosomal abnormalities in fetuses diagnosed with holoprosencephaly.
• To correlate karyotype findings with the presence and type of fetal malformations.

Main Methods:

• Cordocentesis and fetal blood karyotyping were performed on 38 fetuses with diagnosed holoprosencephaly.
• Karyotypes were analyzed and correlated with the presence of isolated HPE, HPE with facial defects, and HPE with extrafacial malformations.

Main Results:

• All 12 cases of isolated HPE and 5 cases of HPE with facial defects only had normal karyotypes.
• Among 21 fetuses with HPE and extrafacial malformations, 11 (52%) exhibited chromosomal abnormalities, including trisomy 13 and trisomy 18.
• In the chromosomally normal group, parental consanguinity was noted in 2 cases and recurrence of HPE in 3 cases.

Conclusions:

• Chromosomal abnormalities are frequently identified in fetuses with holoprosencephaly, particularly when accompanied by extrafacial malformations.
• Karyotyping is a critical diagnostic tool for fetuses with HPE and associated anomalies.
• Genetic evaluation is important for understanding the recurrence risk and providing appropriate genetic counseling.