Genetic counseling and "molecular" prenatal diagnosis of holoprosencephaly (HPE)

Area of Science:

• Developmental Biology
• Medical Genetics
• Prenatal Diagnosis

Background:

• Holoprosencephaly (HPE) is a severe congenital brain malformation with variable phenotypes and causes.
• Accurate genetic counseling and diagnosis are crucial for affected families due to HPE's poor prognosis in severe forms.
• Traditional diagnosis relies on fetal imaging, but molecular testing is increasingly important.

Purpose of the Study:

• To evaluate the utility of molecular prenatal diagnosis for holoprosencephaly (HPE).
• To assess the accuracy of molecular testing in reassuring parents or identifying affected fetuses.
• To analyze the correlation between molecular findings and clinical outcomes in HPE cases.

Main Methods:

• Performed 15 molecular prenatal diagnoses using chorionic villi or amniotic fluid.
• Tested for previously identified HPE-associated mutations in fetuses.
• Correlated molecular results with subsequent fetal imaging (ultrasound, MRI) and postnatal outcomes.

Main Results:

• In 8 cases, the absence of a known mutation reassured parents; subsequent fetal MRI was normal, and children were healthy.
• In 7 cases, the mutation was detected; 4 children were born asymptomatic or with less severe forms than the index case.
• Molecular prenatal diagnosis provided crucial information for family counseling and management decisions.

Conclusions:

• Molecular prenatal diagnosis is a valuable tool for holoprosencephaly (HPE), complementing fetal imaging.
• Testing for known mutations can effectively reassure families or identify affected fetuses, guiding clinical management.
• Interpreting molecular results requires caution due to incomplete genotype-phenotype correlations.