Chromosome 22q11.2 deletion syndrome, also known as velocardiofacial syndrome, DiGeorge syndrome, and CATCH-22, as well as by other names, is one of the most common multiple-anomaly syndromes. The prevalence is often quoted as 1 in 4000, a likely underestimate. Shprintzen estimates that the true prevalence is 1 in 600. The most frequently observed deletion is a 3.0-Mb deletion with the loss of about 40 genes. The phenotypic spectrum varies considerably, and >180 clinical features have been described. Although the inheritance is autosomal dominant, the majority of newly diagnosed cases occur de novo.
The 22q11.2 deletions are mostly frequently identified in infancy or childhood. Evaluation for 22q11.2 deletion should be considered for any neonate with a conotruncal heart lesion, hypocalcemia, and/or cleft palate and should be evaluated in older children or adults with characteristic facial features, developmental delays, palatal anomalies, hypernasal speech, and psychiatric problems.
The 22q11.2 deletions have been associated with autoimmune diseases, including autoimmune thyroid disease. In the present case, the underlying hypoparathyroidism was not identified until the patient had been diagnosed with and treated for hyperthyroidism. Interestingly, the patient had had a history of low and low-normal calcium results in childhood.
Hypercalcemia secondary to hyperthyroidism or thyrotoxicosis is common but is usually mild. Thyroid hormone stimulates bone resorption and increases markers of bone resorption, including C-telopeptide, N-telopeptide, and deoxypyridinoline. Parathyroid hormone (PTH) is decreased in nonparathyroid hypercalcemia. Early reports of increased PTH may have been due to the limitations of early PTH methods, including their measurement of inactive PTH fragments.
The hypocalcemia observed in many neonates with 22q11.2 deletions generally improves during the first year of life as the parathyroids hypertrophy. In this patient, the ability of the parathyroids to compensate may have been temporarily reduced because of the thyrotoxicosis-mediated increase in serum calcium. Treatment of the hyperthyroidism caused hypocalcemia when the parathyroids could not acutely compensate for the hypocalcemia and led to the diagnosis.
Author Contributions: All authors confirmed they have contributed to the intellectual content of this paper and have met the following 3 requirements: (a) significant contributions to the conception and design, acquisition of data, or analysis and interpretation of data; (b) drafting or revising the article for intellectual content; and (c) final approval of the published article.
Authors' Disclosures or Potential Conflicts of Interest: No authors declared any potential conflicts of interest.
Role of Sponsor: The funding organizations played no role in the design of study, choice of enrolled patients, review and interpretation of data, or preparation or approval of manuscript.
- Received for publication February 28, 2011.
- Accepted for publication March 8, 2011.
- © 2011 The American Association for Clinical Chemistry