Adult-recognized 22q11.2 deletion syndrome in adult neurology practice: a brief report of two diagnostic pitfalls
Background 22q11.2 deletion syndrome (22q11.2DS) may be overlooked in adults when neurological care is prompted by pyramidal, gait, or parkinsonism-mimicking presentations rather than by congenital, developmental, psychiatric, or systemic features. Methods We retrospectively reviewed the clinical, imaging, and genetic findings of two unrelated adults whose neurological presentations led to whole-exome sequencing-based copy-number variant (CNV) detection of 22q11.21 deletions. Orthogonal confirmation by chromosomal microarray, multiplex ligation-dependent probe amplification (MLPA), quantitative polymerase chain reaction (qPCR), fluorescence in situ hybridization (FISH), or copy-number variation sequencing (CNV-seq) was not available; therefore, the reported deletion sizes and coordinates represent WES-derived estimates. Results Patient 1 presented with progressive lower-limb weakness, a spastic unsteady gait, pyramidal signs, dysarthria, and ataxic features, together with learning difficulty, palatal abnormalities, and a maternal history of similar gait disturbance and suspected epilepsy; analysis identified a 2.67-Mb deletion at 22q11.21. Patient 2 presented with progressive limb weakness, dysarthria, parkinsonism-mimicking rigidity and slowness, bilateral basal ganglia calcification, abnormal globus pallidus MRI signals, developmental delay, psychiatric symptoms, craniofacial features, and a maternal history of similar motor and cognitive impairment; analysis identified a 2.52-Mb deletion at 22q11.21. Conclusion These cases highlight diagnostic pitfalls and syndromic clues rather than establish a new mechanism. In adult neurology practice, developmental history, palatal or craniofacial abnormalities, basal ganglia calcification, psychiatric symptoms, and family history should prompt consideration of 22q11.2DS and genetic testing that is sensitive to copy-number variants.