Abstract
Autosomal recessive variants in the adenosine deaminase, tRNA specific 3 (ADAT3) gene cause a syndromic form of intellectual disability due to a loss of ADAT3 function.
This disorder is characterized by developmental delay, intellectual disability, speech
delay, abnormal brain structure, strabismus, microcephaly, and failure to thrive.
A small subset of individuals with ADAT3 deficiency have other structural birth defects
including atrial septal defect, patent ductus arteriosus, hypospadias, cryptorchidism,
and micropenis. Here, we report a sibling pair with novel compound heterozygous missense
variants that affect a conserved amino acid in the deaminase domain of ADAT3. These
siblings have many of the features characteristic of this syndrome, including, intellectual
disability, hypotonia, esotropia, failure to thrive, and microcephaly. Both had gastroesophageal
reflux disease (GERD), feeding problems, and aspiration requiring thickening of feeds.
Although they have no words, their communication abilities progressed rapidly when
they began to use augmentative and alternative communication (AAC) devices. One of
these siblings was born with an anterior congenital diaphragmatic hernia, which has
not been reported previously in association with ADAT3 deficiency. We conclude that
individuals with ADAT3 deficiency should be monitored for GERD, feeding problems,
and aspiration in infancy. They may also benefit from the use of AAC devices and individualized
educational programs that take into account their capacity for nonverbal language
development. Additional studies in humans or animal models will be needed to determine
if ADAT3 deficiency predisposes to the development of structural birth defects.
Keywords
ADAT3 - mental retardation autosomal recessive 36 - syndromic intellectual disability
- congenital diaphragmatic hernia - augmentative and alternative communication devices
