# Genetic and Epidemiological Aspects of Louis-Bar Syndrome Transmission: The Impact of Consanguineous Marriages on the Incidence of Hereditary Disorders

## TL;DR

This study examines how consanguineous marriages in Kyrgyzstan increase the risk of Louis-Bar syndrome, a hereditary disorder marked by neurological and immunological symptoms.

## Contribution

The study provides a clinical and genetic analysis of Louis-Bar syndrome in a consanguineous family, identifying a specific ATM gene mutation.

## Key findings

- Consanguineous marriages increase the risk of Louis-Bar syndrome by promoting inheritance of identical mutant alleles.
- A homozygous c.5932G > A mutation in the ATM gene was identified in three affected siblings.
- Clinical manifestations included cerebellar ataxia, telangiectasias, and immunodeficiency in all affected children.

## Abstract

The aim of this study was to investigate the genetic and epidemiological aspects of Louis-Bar syndrome transmission in the population of Kyrgyzstan, with a particular focus on the impact of consanguineous marriages.

The study presents a clinical case of a family with three children affected by this disorder. All children exhibited characteristic manifestations, including progressive cerebellar ataxia of varying severity; conjunctival and cutaneous telangiectasias; recurrent infections; and delayed psychomotor development. In the eldest child, the clinical presentation resembled the ataxic form of cerebral palsy. Standardised scales assessing motor, manual, and communicative functions were used to evaluate the severity of ataxia.

Brain magnetic resonance imaging confirmed cerebellar atrophy in the eldest child and cerebellar subatrophy in the middle and youngest children. All children demonstrated telangiectasias on the mucous membranes of the eyes and skin, as well as signs of immunodeficiency manifesting as frequent infections. Family pedigree analysis revealed consanguinity in the third generation (the maternal grandmother and paternal grandfather were biological siblings). Molecular genetic testing identified a homozygous c.5932G > A mutation in the ATM gene encoding a protein involved in DNA repair.

The findings confirm that consanguineous unions increase the risk of developing Louis-Bar syndrome, as they elevate the likelihood of inheriting identical mutant alleles. This study highlights the importance of medical-genetic counselling and prenatal diagnostics in families at high risk of hereditary diseases, particularly in regions with a high prevalence of consanguineous marriages.