P15.11: Holoprosencephaly at prenatal ultrasound: different etiologies for the same ultrasound finding

Abstract

Objectives: To assess the possibility of finding an etiology in a prenatal diagnosis of holoprosencephaly. Methods: From 1996–2009, 11116 prenatal diagnoses through CVS or amniocentesis were performed in a single center. Every diagnosis of holoprosencephaly at ultrasound was considered. Gestational age, ultrasound findings and karyotype were recorded. When relevant, molecular diagnosis or parental karyotype was studied. Results: 22 fetuses were diagnosed with holoprosencephaly (0.19%). Mean gestational age was 19 weeks. All cases had additional ultrasound findings (100%). A definitive etiology was found in 18 cases (81.8%): Karyotype was abnormal in 14 cases (63.6%) and normal in 8 (36.4%). There were 10 free trisomies (9 trisomies 13 and 1 trisomy 18), 4 structural chromosomal anomalies (3 inherited from parental balanced translocations and one de novo). In the group with normal karyotype: one autosomal dominant mutation of gene SIX was diagnosed. Both parents tested negative. One case had a postnatal diagnosis of dysgnathia complex. Two fetuses had Smith Lemli Opitz: low cholesterol levels at cordocentesis and 2 mutations at the gene DHCR were found. Both parents were carriers. In four cases with normal karyotype no etiology was found: in one case, no results were achieved due to a cytogenetic culture failure and in three other cases no etiology could be found. Conclusions: Our results showed that a definitive etiology can be achieved in 8 out of 10 cases when holoprosencephaly is found at a prenatal ultrasound. The fact that holoprosencephaly is strongly associated with chromosomal anomalies was supported with our data. However, in euploid fetuses, the searching for a molecular diagnosis is warranted since different genes with different patterns of inheritance may be responsible for this malformation. The finding of parents carrying mutations or structural chromosome balanced rearrangements is crucial for planning PGD in future pregnancies.