Holoprosencephaly at prenatal diagnosis: analysis of 28 cases regarding etiopathogenic diagnoses

Abstract

Objective: To assess the likelihood of finding an etiopathogenic cause in an ultrasonographic prenatal diagnosis of holoprosencephaly.

Materials and methods: From January 1996 to June 2010, 13 883 prenatal diagnoses through chorionic villus sampling or amniocentesis were made. Every fetus with holoprosencephaly at ultrasound was evaluated. Gestational age, additional ultrasound findings, and fetal karyotype were recorded. Molecular diagnosis and parental karyotype were studied, if relevant.

Results: Twenty-eight fetuses were diagnosed with holoprosencephaly (0.20%). All cases had additional ultrasound findings (100%). A definitive etiology was found in 23 cases (82.14%): karyotype was abnormal in 19 (67.9%) and normal in 8 (28.5%) cases. In the normal karyotype group, although molecular testing was performed in a few cases, one mutation of gene SIX 3 was diagnosed, one diagnosis of dysgnathia complex was made, and two fetuses presented Smith-Lemli-Opitz syndrome. No etiopathogenic diagnosis was made in five fetuses.

Conclusions: Our results showed that a definitive etiology can be established in most cases of prenatal holoprosencephaly. Chromosomal anomalies were the most frequent finding. However, in euploid fetuses, molecular diagnosis is worthwhile, as different genes with different inheritance patterns may be responsible for this malformation. Thorough evaluation proved beneficial for assessing more accurate prognosis and recurrence risks.