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J Pediatr Genet 2022; 11(03): 253-256
DOI: 10.1055/s-0040-1718536
Case Report

Retrospective Diagnosis of Pontocerebellar Hypoplasia Type 1B in a Family with Two Deceased Newborn Children

Irena Bradinova 
1   National Genetic Laboratory, University Hospital of Obstetrics and Gynecology “Maichin dom,” Medical University Sofia, Bulgaria
,
Silvia Andonova
1   National Genetic Laboratory, University Hospital of Obstetrics and Gynecology “Maichin dom,” Medical University Sofia, Bulgaria
,
Alexey Savov
1   National Genetic Laboratory, University Hospital of Obstetrics and Gynecology “Maichin dom,” Medical University Sofia, Bulgaria
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Abstract

Pontocerebellar hypoplasia type 1B is a severe autosomal recessive neurologic disorder characterized by a combination of cerebellar and spinal motor neuron degeneration beginning at birth. Pontocerebellar hypoplasia type 1B is caused by mutations in EXOSC3 gene. High prevalence of the p.Gly31Ala mutation was found recently, especially in the Roma ethnic minority. We present a young Bulgarian Roma family with two deceased newborn children manifesting severe neuromuscular disorder including severe muscle weakness, respiratory distress, and multiple joint contractures. Based on the clinical signs and family's population characteristics, DNA testing for the previously described EXOSC3 in Bulgarian Roma mutation c.92G > C; p.Gly31Ala was performed on blood samples of both parents and they were found to be heterozygous carriers. This finding indirectly confirmed the diagnosis of pontocerebellar hypoplasia type B in the deceased offspring. Knowledge of population-specific molecular bases of genetic conditions was the key to final diagnosis in the presented family. Designing of population-based clinical-genetic panels may be a powerful diagnostic tool for patients with such origin. Preconception carrier screening in high-risk population groups is a feasible option to discuss.

Keywords

Pontocerebellar hypoplasia type 1B - EXOSC3 gene - spinal muscular atrophy - Roma population genetic diseases


Publication History

Received: 07 August 2020

Accepted: 01 September 2020

Article published online:
08 October 2020

© 2020. Thieme. All rights reserved.

Georg Thieme Verlag KG
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