Abstract
Webb–Dattani syndrome (WEDAS) is an autosomal recessive disorder caused by mutation
in the ARNT2 gene characterized by frontotemporal hypoplasia, globally delayed development, and
pituitary and hypothalamic insufficiency. The condition is reported to be associated
with consanguinity and with Saudi Arabian ancestry. Here we describe a family of three
affected siblings born to healthy second cousin parents of Saudi Arabian ancestry.
The children presented at 3 months of age with congenital central hypotonia and hypoventilation,
central diabetes insipidus, multiple pituitary hormone deficiency, severe developmental
delay, acquired microcephaly, cortical blindness with normal retinal examination,
seizures, and gastroesophageal reflux. Whole exome sequencing detected a homozygous
unclear variant (c.378C>T; p.G126G) in the ARNT2 gene in both the affected twins. According to splice prediction programs, this variant
results in the creation of a cryptic donor splice site, possibly leading to a loss
of function. These data support the role of the detected mutation in the ARNT2 gene in causing the described phenotype.
Keywords
WEDAS - Webb–Dattani -
ARNT2
