Genetic Etiology in Children with Progressive Neuroregression.

OBJECTIVES

To determine the genetic etiology in children presenting with progressive neuroregression and to evaluate the utility of clinical examination, neuroradiology, biochemical and molecular tests in reaching a final diagnosis by pattern recognition and clinical correlation.

METHODS

This was an ambispective observational study conducted at a tertiary care genetic centre in New Delhi. The study comprised 130 patients upto age 18 y with progressive neuroregression with other neurological signs, in whom a genetic etiology was determined.

RESULTS

The overall diagnostic yield was 79.2% (103/130) with highest yield in age of onset < 1 y (84.3%, 43/51). The most common co-morbidity was abnormalities of tone (83%) followed by seizures (47%). A total of 43 different disorders were identified, with neurometabolic disorders comprising the largest group (85.4%) and lysosomal storage disorders comprising the largest sub-group (46.6% of total). The diagnosis was established by biochemical methods in 43 cases (42%), while molecular genetic tests determined the etiology in 60 cases (58%).

CONCLUSIONS

This is the first study describing the spectrum of disorders presenting with neuroregression in an Indian cohort. It also delineates the utility of different testing methodologies in achieving the final diagnosis, which helps define the diagnostic approach in resource limited settings for a rapid diagnosis. A confirmed genetic etiology aids in improved management as well as genetic counseling for recurrence risk assessment and future reproductive options.