Development:
• Severe global developmental delay (all individuals)
• Profound motor delay, no independent ambulation achieved (all individuals)
• Absent functional speech (most individuals)
• Psychomotor regression (most individuals)
• Sleep disturbances (most individuals)
• Behavioural symptoms (some individuals)
Seizures:
• Early-onset intractable seizures, onset in the first year of life (all individuals)
• Recurrent status epilepticus (some individuals)
• Poor response to antiseizure medications (all individuals)
• EEG: generalised slowing and encephalopathy pattern (all individuals)
Neurological Examination:
• Severe infantile hypotonia (all individuals)
• Brisk deep tendon reflexes (most individuals)
• Abnormal involuntary movements (most individuals)
Neuroimaging:
• Delayed or incomplete myelination (all individuals)
• Progressive cerebral atrophy with white matter volume loss and ventricular dilatation (all individuals)
• Increased cerebral subarachnoid spaces (all individuals)
• Reduced basal ganglia volume, particularly caudate nuclei and thalami (all individuals)
• Small hippocampi (some individuals)
Craniofacial features:
• Frontal prominence (all individuals)
• High anterior hairline and high forehead (most individuals)
• Dolichocephaly (some individuals)
• Intertemporal narrowing (some individuals)
• Thin, highly arched eyebrows, occasionally with medial flare (most individuals)
• Strabismus (most individuals)
• Upslanting palpebral fissures (some individuals)
• Long eyelashes (some individuals)
• Broad nasal bridge (most individuals)
• Bulbous nasal tip (most individuals)
• Tented upper lip (most individuals)
• Large, low-set ears with prominent antihelix (most individuals)
Prognosis:
• Progressive disease course
• Early mortality in infancy and childhood reported across multiple families
MDGA2