Clinical characteristics are variable across the five autosomal dominant cases. Each case possessed a different and novel de novo heterozygous GATAD2A variant, with this range of genotypes likely playing a factor in the range of phenotypic features. This range included issues with the CNS, heart, kidney, eye, and other organ systems. The most common features included global developmental delay (GDD; 4/5) and craniofacial dysmorphology (3/5).
GDD was associated with speech delay (4/4) and autistic features (1/4). Structural brain defects were noted in 2/5 cases (ventriculomegaly, thin corpus callosum), although 3/5 cases were not neuroimaged.
Craniofacial dysmorphisms included macrocephaly (2/3), prominent forehead (2/3), deep set eyes (2/3), broad nasal root (2/3), broad nasal tip (1/3) and hypertelorism (1/3).
Other variable phenotypic features included; heart defects (2/5; PDA, VSD, atrial enlargement), kidney defects (2/5; bilateral hydronephrosis, horseshoe kidney, and bilateral Wilms tumor), ophthalmologic defects (2/5; optic nerve coloboma, microphthalmia, small optic nerves on MRI); hemi-hypertrophy (2/5); and an imperforate anus (1/5).
Obviously, there is a need for more GARND cases to identify a more unifying phenotype if one exists. Our ongoing research hopes to find and report further cases with GATAD2A variants.
GATAD2A