Inbreeding as a Cause of Congenital Hydrocephalus

Ab s t r Ac t Aim: The aim of the study was to determine the role of inbreeding in occurrence of lethal congenital hydrocephalus (LCH) and congenital abnormalities associated with it. Materials and methods: There was an examination of 182 fetuses born with LCH, out of which 69 were diagnosed with isolated and 113 fetuses were diagnosed with associated hydrocephalus resulting in 38% and 62% occurrences, respectively. All the fetuses were the result of spontaneous abortions, stillbirths, neonatal deaths and the pregnancy terminations due to medical reasons. The fetal autopsy was performed immediately after the fetal expulsion. The brain examination was performed after being preserved in 10% formalin solution for the period of 6 months. Measurements were taken on the ventricles in their central parts. Ventricles with the enlargements over 10 mm were determined as hydrocephalus and severe ventriculomegaly if the ventricular dimensions were over 15 mm. Results: Lethal congenital hydrocephalus associated with were the presence of previous pregnancies with inbreeding and malformations [OR = 7.309 CI 95% (1.806–29.584)]; the maternal age over 40 and the third-degree inbreeding in fetus [OR = 18.500 CI 95% (1.410–638.150)]; agenesis of the corpus callosum in fetuses born from mothers in close relative marriages [OR = 30.000 CI 95% (1.410–638.150)]; aqueductal stenosis [OR = 9.867 CI 95% (1.328–73.296)]; skeletal dysplasia [OR = 6.727 CI 95% (1.203–37.609)]; and Dandy–Walker syndrome [OR = 6.250 CI 95% (0.803–48.671)]. Conclusion: The obtained results unambiguously prove the importance and significance of inbreeding as a risk factor of LCH appearance and its increase in association with other risk factors which should be taken into consideration when observing such pregnancies. Clinical significance: Lethal congenital hydrocephalus is the result of a significant number of risk factors and is often associated with other malformations. Currently, prenatal ultrasound is able to visualize ventriculomegaly. It is important to gather information about the previous pregnancies and the type of marriage among close relatives. In case of ventriculomegaly it is imperative to carry out MRI and genetic testing that can provide additional information. In the case of medical abortion, stillbirth or neonatal death, a fetopathological study must be carried out which enriches our knowledge of malformations, complements and directs the ultrasound examination, modifies genetic counseling and determines the behavior to be followed when taking responsibility for a new, subsequent pregnancy.