P 1008. Neuronal Migration Disorders in Infants with 22q11.2 Deletion Syndrome—Two Case Reports

Background: First described in 1996, 22q11.2 microdeletion syndrome rarely may be associated with complex neuronal migration disorders such as cortical dysplasia of pachygyria–polymicrogyria spectrum. Currently, 30 cases are known in the literature, as well as single cases of associated CNS anomalies including agenesis of corpus callosum, hippocampal malrotation, and cerebellar hypoplasia. Here, we report on two patients with pachygyria–polymicrogyria and 22q11.2 deletion without cardiac or immunological manifestation.

Case Report: Two male infants presented for further evaluation of global psychomotor retardation. Patient 1 (male) presented at the age of 4 months with hypertonic developmental coordination disorder, opisthotonus, anorectal malformation, retrognathism, and nutritional problems. Ophthalmological findings were normal. Head growth was below normal range for age (2 perc.,−2,1 SDS). Standardized developmental assessments at the age of 12 months were not feasible due to significant mental and motor retardation. Metabolic etiology was unlikely based on laboratory screening tests. Epileptiform discharges were repeatedly found in the right frontocentral region without evidence of clinical seizures. Cranial magnetic resonance imaging (MRI) revealed bilateral pachygyria–polymicrogyria. Microarray analysis for specific anomalies detected a 2.8 Mb sized copy reduction in the long arm of chromosome 22 (22q11.2). Cardiac and immunological evaluations were without pathological findings.

Patient 2 (male) presented at the age of 7 months for further evaluation of secondary microcephaly (head circumference <1 percentile, −3.9 SDS), psychomotor retardation, and hypertonic movement disorder. History of perinatal asphyxia and hypoxic-ischemic encephalopathy (HIE) was reported. There were no signs of facial dysmorphia. Repeated EEG showed epileptiform discharges in the right centroparietal region without evident clinical seizures. Cranial MRI showed bilateral pachygyria–polymicrogyria without classical findings of perinatal HIE. Microarray analysis detected 22q11.2 microdeletion. Cardiac and immunological evaluations were without pathological findings.

Conclusion: Our case reports confirm the rare association of pachygyria–polymicrogyria spectrum with 22q11.2 microdeletion without classical main features such as heart disease, immunodeficiency, hypocalcemia, and hypoparathyroidism. Incomplete phenotypes of 22q11.2 deletion syndrome may be limited to neuronal migration disorders and refractory epilepsy without cardiac or immunological manifestations. Confirming diagnosis is of clinical significance regarding therapeutic as well as preventive options.