HIVEP2 disorder is associated with various neurodevelopmental impairments and systemic features.
Neurodevelopmental features
The early childhood presentation of HIVEP2 disorder is characterized by global developmental delay with impairments in cognitive, language, and motor abilities. Language acquisition may be slowed, and sometimes affected individuals may be nonverbal. Hypotonia can accompany delayed acquisition of motor milestones. Gait may be wide-based and unsteady.
There is a spectrum of neurodevelopmental disorders associated with HIVEP2 disorder. Intellectual disability, of varying degrees of severity, and autism spectrum disorder are common. Behavioural features include attention deficit hyperactivity disorder, anxiety, and aggression.
Minor structural abnormalities of the brain have been reported. Affected individuals may have microcephaly. MRI of the brain may show non-specific abnormalities, such as dysgenesis of the corpus callosum.
Epilepsy occurs with a relatively low prevalence in HIVEP2 disorder. From previously published data, about 20% have a history of seizures. Seizure severity in HIVEP2 disorder can range from infrequent (once every few years) to frequent (multiple seizures/day). Both focal onset (focal onset impaired awareness seizures) and generalized seizures (generalized tonic clonic, myoclonic seizures) have been reported.
Facial dysmorphisms
Affected individuals have variable facial dysmorphisms. These include widely spaced eyes, broad nasal bridge, upturned nose, and tapering fingers.
Ophthalmological features
Mild ophthalmological features may be common in HIVEP2 disorder. These include strabismus, farsightedness, and astigmatism.
Gastrointestinal features
Gastroesophageal reflux and constipation are two associated gastrointestinal complications of HIVEP2 disorder.
Miscellaneous
Frequent ear infections may occur with HIVEP2 disorder.
In general, cardiovascular defects are not prominently associated. Renal and urogenital anomalies are not a common manifestation of HIVEP2 disorder, though there is one report of vesicoureteral reflux.