P 05.16: Family case of holoprosencephaly

Holoprosencephaly is a heterogeneous group of diseases. It is caused by a full or partial lack of separation of the embryonic prosencephalon into two different hemispheres. It may be associated with malformations in the central part of the face. It is often caused by the mother's exposure to teratogens in the first weeks of pregnancy or chromosomal aberrations or may be caused by multiple factors. Hereditary holoprosencephalies are described as autosomal dominant diseases with a varied penetration or autosomal recessive or X-linked syndromes. A 37-year-old white woman, II gravida, II para. Her first pregnancy was terminated by induced abortion for hypoplasia of the left heart (a different partner). In her second pregnancy, an ultrasound scan in the first trimester identified the absence of the falx cerebri in the frontal part, and the condition was diagnosed as semilobar holoprosencephaly. The parents decided to continue the pregnancy. Amniocentesis performed at GW 15 revealed normal karyotype 46, XY, array-CGH (Bluegnome) screening for microdeletion syndromes negative. Ultrasound finding of the fetus unchanged. At GW 16, the parents decided to terminate the pregnancy. At the parents' request, no autopsy was performed on the fetus, external fetus morphology revealed no pathologies. Genetic tests of both parents performed - normal karyotypes found. Both parents sent for a CT brain scan, which revealed a partial fusion of the parietal lobes in the midline over the body of the lateral ventricles in the female - lobar holoprosencephaly. She was without significant neurological problems and led a normal social life. According to a genetic consultation, she most likely suffers from an autosomal dominant disease with variable expressivity and a 50% risk of recurrence in the next pregnancy. In this work, we aim to draw attention to the possibility of familial occurrence of holoprosencephaly with potentially variable expression of the disease.