Endocrine Abstracts

Microdeletions or microduplications in the 22q11.2 region cause a variety of disorders, including DiGeorge syndrome (DGS; MIM 188400), velocardiofacial syndrome (VCFS; MIM 192430) and cat-eye syndrome (CES; MIM 115470). DGS and VCFS clinically overlap and are both caused by three million-base pair (Mb) deletions on the chromosome region 22q11.2, flanked by low copy number repeats (LCRs) labeled ‘A-D’. The most common deletion, present in 85% of individuals, extends from A to D and includes TBX1, a gene deemed responsible for typically associated features, in particular conotruncal cardiac anomalies. The remaining 15% of affected individuals have atypical ‘nested’ deletions. Deletion of genes within the DiGeorge chromosome region (DGCR) is the only genetic abnormality known to be associated with 22q11.2. The 22q11.2 deletion syndrome is suspected in individuals with a range of findings including congenital heart disease (particularly conotruncal defects), palatal abnormalities, hypocalcemia, immune deficiency, learning difficulties, hearing loss and characteristic facial features, among other structural anomalies. We report a 24-year-old female patient with severe primary hypoparathyroidism (PHP), seizures during the 1st and 2nd year of life, intellectual disability, bilateral sensorineural hearing loss, microcephaly, dysmorphic facial features, severe myopia and recurrent infections. Heart ultrasound has not been performed yet. Her father is known to have hearing loss, intellectual disability, arthritis, myopia and astigmatism. The patient was diagnosed with PHP at 12 years old, when she required multiple hospitalizations in an Intensive Care Unit for symptomatic hypocalcemia resistant to oral treatment. She was medicated with calcium citrate 3.8 g orally per day, Calcium Carbonate 1.5 g orally per day and Calcitriol 3 ucg. She required weekly hospitalizations for hypocalcemia, receiving IV calcium gluconate with regular clinical and metabolic response and digestive intolerance. She started with recombinant PTH 1-84, 50 ucg diary, with a good clinical and biochemical improvement. We performed molecular diagnosis consisting of MLPA (multiple ligation probe amplification) employing the SALSA P250 MLPA kit. The analysis of copy number variations, revealed a deletion of 1.5 Mb in the 22q11 region ranging from LCR22-A to LCR22-B. Since the approximately 10 percent of cases is inherited, a molecular study was performed in the patient’s parents with pending results.