Case report: Central 22q11.2 Deletion Presenting in Adulthood with CAKUT, Malignant Hypertension and Thoracoabdominal Aortopathy

Abstract Background Congenital anomalies of the kidney and urinary tract (CAKUT) are among the leading causes of chronic kidney disease (CKD) and are increasingly recognized to have a genetic basis. Pathogenic copy number variants (CNVs), particularly those involving chromosome 22q11.2, represent important but frequently underrecognized causes of syndromic CAKUT. Central 22q11.2 deletions, which spare TBX1 while encompassing CRKL , often lack the classic manifestations of DiGeorge syndrome and may therefore remain undiagnosed until adulthood. Case presentation We report a 40-year-old woman with congenital solitary functioning kidney secondary to left kidney hypoplasia, longstanding resistant hypertension, and ischemic stroke in the setting of malignant hypertension. Vascular imaging demonstrated multifocal narrowing of the descending thoracic and abdominal aorta with extensive collateralization, consistent with developmental arteriopathy. Additional findings included craniofacial and dental abnormalities, learning difficulties, and a family history of chronic kidney disease, stroke and developmental delay. Comprehensive genomic testing using a CAKUT-focused next-generation sequencing panel with integrated CNV analysis identified a heterozygous pathogenic 954.8-kb central 22q11.21 deletion spanning the LCR22B–D interval and encompassing CRKL while sparing TBX1 . Conclusions This case expands the adult phenotype associated with central 22q11.2 deletion syndrome and illustrates how developmental kidney and vascular abnormalities may remain unrecognized for decades in the absence of the classic features of DiGeorge syndrome. Recognition of the underlying genomic disorder reclassified the patient's vascular disease as a developmental arteriopathy rather than an acquired inflammatory process, with important implications for surveillance, therapeutic decision-making, genetic counseling, and cascade testing. Central 22q11.2 deletions are an underrecognized cause of syndromic CAKUT in adults and as illustrated, may also underlie developmental large-vessel arteriopathy. Adults presenting with CAKUT, severe or resistant hypertension, unexplained large-vessel abnormalities, or additional extra-renal manifestations should undergo comprehensive genomic evaluation that includes CNV analysis to establish a molecular diagnosis and guide clinical management.