Background: West syndrome (WS) is characterized
by the onset of epileptic spasms usually within the first year of life.
Global developmental delay with/without regression is common. Advances in
high-throughput sequencing have supported the genetic heterogeneity of this
condition. To better understand the genetic causes of this disorder, we
investigated the results of targeted exome sequencing in 29 patients with
WS. Methods: Whole exome sequencing (WES) was
performed on an Ion ProtonTM and variant reporting was
restricted to sequences of 620 known epilepsy genes. Diagnostic yield and
treatment impact are described for 29 patients with WS.
Results: A definitely/likely diagnosis was made
in 10 patients (34%), which included 10 different genes (ALG13,
PAFAH1B1, SLC35A2, DYNC1H1, ADSL, DEPDC5, ARX, CDKL5, SCN8A,
STXBP1) known to be associated with epilepsy or WS. Most
variants were de novo dominant
(X-linked/autosomal) except for ARX (X-linked
recessive) and ADSL (autosomal recessive). 4 out
of 10 (40%) had a genetic diagnosis with potential treatment implications.
Conclusions: These results emphasize the genetic
heterogeneity of WS. The high diagnostic yield, along with the significant
genetic variability, and the potential for treatment impact, supports the
early use of this testing in patients with unexplained WS.
Community‐based recruitment and exome sequencing indicates high diagnostic yield in adults with intellectual disability
