Per our initial study, the clinical presentation of GAND subjects was relatively consistent between GAND individuals. One exception was that GAND individuals with a type of DNA variant called “missense variants” had an increased risk of developing seizures, compared to other types of variants (nonsense, frameshift).
Current research is evaluating larger numbers of GAND children with less typical variant types (missense and splice-site) to determine if these differences are consistent when examining larger groups of GAND individuals.
Pregnancies were mostly without complications, with the exception of increased amniotic fluid (polyhydramnios, 45%). Significantly enlarged head circumference was frequently present at birth (69%) and became more common as children got older (91.8%). All subjects had developmental delay and intellectual disability. All subjects had low tone during infancy and delayed motor milestones, such as sitting up and walking. Most children learned to ambulate. A majority of subjects were noted to have infantile feeding difficulties and reflux disease (82%).
These oro-mechanical issues were also associated with delayed and limited ability to speak in all subjects consistent with childhood apraxia of speech. The ability to understand language and words was not as severely affected, with most children being able to follow multistep commands at older ages.
Seizures were present in a minority of subjects (24%) with most children responding well to antiepileptic treatment.
Neuroimaging was abnormal in the majority of subjects (60%), with common features including enlarged spaces between the brain and skull along with decreased insulation of nerve projections and thin corpora callosi.
Almost all subjects made good eye contact and exhibited social reciprocity.
Toilet training was not attained in the majority of subjects.
Most subjects had eye and visual issues that included strabismus (88%), which was sometimes associated with other structural issues of the eye.
A minority of subjects were born with aortic valves that had only two instead of three leaflets (~10%, compared with 2% in the general population), with two subjects requiring surgical intervention to widen the valve opening.
Facial features were evaluated in 37 GAND children in our initial study with the distinct “GAND facial appearance” (in other words the children looked like siblings because they possessed these features) including a high wide forehead (100%), prominent browlines (62.2%), wide-set eyes (78.4%), downslanting eyes (45.6%), prominent or bulbous nasal tip (83.8%), short space between the nose and top of lip (philtrum; 51.3%) and a pointed chin (91.9%). These features have been consistent since the original publication.
GATAD2B