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Título

CENTRAL CONGENITAL HYPOTONIA: WHAT IS THE FIRST GENETIC TEST OF CHOICE?

Introdução

Hypotonia is a frequent neurological manifestation with numerous etiologies, but recognizing the cause is a challenge. First, it’s necessary to differentiate hypotonia as peripheral, central or mixed. Signs of central hypotonia are normo/hyperreflexia, developmental delay, cognitive delay and/or epileptic seizures associated and normal creatine phosphokinase (CPK). After ruling out environmental risk factors, genetic causes should be investigated. Brazil lacks epidemiological studies on these diseases. One of the factors that may influence is the difficulty to perform specific biochemical dosage and genetic testing due to the high cost and difficulty to access in the public health network.

Objetivo

To identify the main diagnostic genetic tests for non-environmental central congenital hypotonias.

Métodos

Descriptive, cross-sectional and retrospective study by reviewing medical records of children evaluated between 2017 and 2022 at the Neurogenetics outpatient clinic at the referral hospital in Salvador-BA. Inclusion criteria were central congenital hypotonia and etiologic diagnosis.

Resultados

Sixty-four children with hypotonia were selected and 14 children met the inclusion criteria. Of this sample, 50% are boys and the age at diagnosis was between 11 and 232 months. Central hypotonia was associated with other neurological syndromes, such as: cognitive (57%), epileptic (43%), neurodevelopment regression (36%), cerebellar (22%), and dyskinetic (14%). The genetic tests performed were karyotype (62.5%), SNP-array (14.5%), genetic panel (21%), whole exome sequencing (14.5%), and whole genome sequencing (50%). The diagnostic non-confirmation rate was 66% karyotype, 32% SNP-array and 7% for clinical exome. In some situations, the genome was the first choice to carry out the diagnostic investigation due to the availability at the reference center. Some patients have had more than one genetic test.

Conclusões

Genome sequencing had the highest diagnostic yield among all genetic tests. Anamnesis and neurological examination are important to guide the etiological investigation and genotype-phenotype correlation, especially in cases with dysmorphism or variants of uncertain significance.

Palavras chave

Central hypotonia, Molecular genetics, Genoma

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Área

Neurogenética