Cardiovascular

Adult-recognized 22q11.2 deletion syndrome in adult neurology practice: a brief report of two diagnostic pitfalls.

TL;DR

Two unrelated adults with progressive neurological presentations were found to have 22q11.2 deletion syndrome, highlighting diagnostic pitfalls when pyramidal, gait, or parkinsonism-mimicking features prompt neurological care rather than the classic congenital or developmental features of the syndrome.

Key Findings

Patient 1 with progressive neurological symptoms was found to carry a 2.67-Mb deletion at 22q11.21 detected by whole-exome sequencing-based copy-number variant analysis.

  • Clinical presentation included progressive lower-limb weakness, spastic unsteady gait, pyramidal signs, dysarthria, and ataxic features.
  • Additional syndromic clues included learning difficulty and palatal abnormalities.
  • Family history was notable for a maternal history of similar gait disturbance and suspected epilepsy.
  • Deletion size and coordinates represent WES-derived estimates, as orthogonal confirmation by chromosomal microarray, MLPA, qPCR, FISH, or CNV-seq was not available.

Patient 2 with parkinsonism-mimicking features was found to carry a 2.52-Mb deletion at 22q11.21 detected by whole-exome sequencing-based copy-number variant analysis.

  • Clinical presentation included progressive limb weakness, dysarthria, parkinsonism-mimicking rigidity and slowness.
  • Neuroimaging findings included bilateral basal ganglia calcification and abnormal globus pallidus MRI signals.
  • Additional syndromic clues included developmental delay, psychiatric symptoms, and craniofacial features.
  • Family history was notable for a maternal history of similar motor and cognitive impairment.
  • Deletion size and coordinates represent WES-derived estimates, as orthogonal confirmation was not available.

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.

  • Both cases were unrelated adults whose 22q11.2DS diagnoses were reached through neurological workup rather than through recognition of classic syndromic features.
  • The authors frame these as 'diagnostic pitfalls' rather than new mechanistic findings.
  • The cases were identified through retrospective review of clinical, imaging, and genetic findings.

Specific clinical features should prompt consideration of 22q11.2DS and genetic testing sensitive to copy-number variants in adult neurology practice.

  • The authors identify developmental history, palatal or craniofacial abnormalities, basal ganglia calcification, psychiatric symptoms, and family history as key syndromic clues.
  • Whole-exome sequencing-based CNV detection was the method used to identify deletions in both patients.
  • The authors note that genetic testing must be sensitive to copy-number variants, as standard sequencing approaches may miss deletions.

What This Means

This research describes two unrelated adults who were diagnosed with 22q11.2 deletion syndrome (also known as DiGeorge syndrome or velocardiofacial syndrome) only after they sought neurological care as adults. In both cases, the initial concern was a progressive movement or motor problem — one patient had spastic walking difficulties and coordination problems, while the other had symptoms resembling Parkinson's disease including stiffness and slowness, along with calcium deposits in a specific brain region. Genetic testing through whole-exome sequencing revealed that both patients had a deletion on chromosome 22, a genetic change that is typically associated with heart defects, immune problems, and developmental issues identified in childhood. The significance of these cases is that 22q11.2 deletion syndrome is commonly diagnosed in infancy or childhood based on distinctive physical features and organ abnormalities, but it can go unrecognized into adulthood when the presenting complaint is neurological. Both patients also had other subtle clues that, in retrospect, pointed toward the syndrome — including learning difficulties, abnormal palate or facial features, psychiatric symptoms, and family members with similar problems. The authors note that the genetic deletion sizes are estimates because full confirmatory testing was not performed, which is a limitation of the study. This research suggests that neurologists evaluating adults with progressive motor problems, movement difficulties, or brain imaging findings like basal ganglia calcification should consider asking about developmental history, look for physical features like palate abnormalities, and take a careful family history. When these features are present alongside neurological symptoms, genetic testing capable of detecting missing segments of chromosomes — not just point mutations — may be warranted to avoid missing a diagnosis of 22q11.2 deletion syndrome.

Have a question about this study?

Citation

Wu D, Wang Y, Sun D, Wang J, Wang X. (2026). Adult-recognized 22q11.2 deletion syndrome in adult neurology practice: a brief report of two diagnostic pitfalls.. Frontiers in neurology. https://doi.org/10.3389/fneur.2026.1933196