Congenital hydrocephalus (CH) affects 1 in 1000 births, is a major cause of morbidity, and costs the US health care system $2 billion annually.1 More than 40% of CH cases are thought to have a genetic etiology. However, only less than 5% of CH cases are associated with a defined gene mutation,1 limiting the utility of genetic testing with targeted approaches and underscoring the need for CH gene discovery. The X-linked recessive form of hydrocephalus associated with aqueductal stenosis (OMIM #307000) owing to mutation of L1 cell adhesion molecule (L1CAM) is the most common form of CH (approximately 3% of total cases),1 and variably presents in male patients with mental retardation, spastic paraparesis, and adducted thumbs as part of L1 syndrome.2 Currently, L1CAM is the only gene for which targeted screening is advised and routinely clinically available for CH; however, there is little consensus on testing criteria or methods.3 Moreover, patients with no family history who present with perinatal CH are most commonly assessed, if at all, by karyotype or microarray analysis aimed at detecting chromosomal abnormalities or copy number variants but unable to identify de novo or inherited rare mutations.4
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Sullivan W, Reeves BC, Duy PQ, et al. Exome Sequencing as a Potential Diagnostic Adjunct in Sporadic Congenital Hydrocephalus. JAMA Pediatr. Published online November 16, 2020. doi:10.1001/jamapediatrics.2020.4878
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