GATAD2B-associated Neurodevelopmental Disorder or GAND, is an autosomal dominant disorder characterized by infantile hypotonia, subjective feeding issues (including in utero polyhydramnios), minor heart defects, strabismus, motor delays, intellectual disability, apraxia of speech, epilepsy and macrocephaly associated with a large broad forehead.
The GATAD2B protein is a subunit paralog in the Nucleosome Remodeling and Deacetylase (NuRD) Complex. The NuRD complex is a multiprotein complex that is intrinsically involved in gene regulation. All NuRD subunits have 2-3 paralogs, which adds complexity to the system; however, some NuRD subtypes have specific roles or expression profiles (GATAD2B-NuRD) that make them very important during neurogenesis and corticogenesis.
The disorder currently has about 400-500 known cases identified (May 2025).
The macrocephaly is not typically associated with megalencephaly, as early neuroimaging shows increased extra-axial spaces (containing CSF fluid) and enlarged ventricles. Other neuroimaging changes can include hypomyelination and white matter signal abnormalities.
Epilepsy can be either focal-onset or primary generalized-onset and is typically responsive to medication, although a few GAND individuals have intractable epilepsy. Epilepsy was seen at a higher incidence with GATAD2B missense variants than other variant subtypes (although sample was low and this is currently under additional investigation).
Minor heart defects tend to involve the aortic valve (bicuspid instead of tricuspid valves) in 8-10% of the initially reported GAND cohort, two of whom required therapeutic intervention for stenotic valves.
There is a somewhat broad range of intellectual disability with some children having significant cognitive disability, while others can perform well with basic tasks. Speech is a limiting feature, with childhood apraxia of speech (CAS) being seen in all GAND individuals. CAS is also associated with other oro-mechanical issues in GAND children, for example neonatal feeding issues and polyhydramnios and sialorrhea.
GATAD2B