Endocrine Abstracts (2019) 64 037 | DOI: 10.1530/endoabs.64.037

The phenotypic diversity of the 22q11.2 deletion syndrome and hypoparathyrodism

Poradosú Sabrina, Velkeniers Brigitte & Bravenboer Bert

Endocrinology Department, Vrije Universitair Ziekenhuis, Brussel, Belgium.

The 22q11.2 deletion syndrome is a clinical syndrome caused by a hemizygous deletion in the chromosome 22q11.2. Clinical findings include cardiac defects, characteristic facial features, thymic hypoplasia, cleft palate, hypoparathyroidism, learning difficulties and psychiatric disorders. The importance of chromosome 22 relies on small number of genes located in the long (Q) arm participating in the development of the body plan, including the pharyngeal arches during the embryonic development. The deletion of this genes can lead to a broad phenotypic heterogeneity resulting in a variety of abnormal clinical features, severity and time of onset, making the diagnosis and management a challenge. Examples of this deletion syndrome are the Velocardiofacial syndrome and the DiGeorge syndrome. We describe three patients, of which two adults and one child, with a proven 22q11 deletion who present different clinical characteristics but all having hypoparathyroidism in common. The first patient is a 64-year-old female who at 34 years of age suffered from a grand mal seizure attributed to a hypocalcemia of 4.8 mg/dl (normal range 8.5–10.2 mg/dl. Information regarding parathyroid hormone and phosphate are not available). The diagnosis of a primary hypoparathyroidism was made, for which treatment with calcitriol and calcium carbonate was started. Nine years later she was diagnosed with an auto immune negative subclinical hypothyroidism (TSH =4.0 mU/l) at our out-patient clinic for which treatment with L-thyroxine was started. She has been a patient of our clinic since 1990. It was only in 2016 when a suspicion of a genetic cause for the combination of hypothyroidism and hypoparathyroidism was made. A 22q11.2 deletion syndrome was confirmed in 2018. Since 1989 she has not have any other seizures and no other organs affected by this syndrome have been reported. Our second patient is a 54-year-old male known to have renal abnormalities (bilateral urethra stenosis with hydronephrosis), severe mental retardation, deafness, repetitive otitis and upper airway infections during childhood, arterial hypertension, Graves hyperthyroidism treated by total thyroidectomy after a long treatment with thiamazol and a history of seizures attributed to hypocalcemia of as low as 6.7 mg/dl when the patient was 37 years old before the thyroidectomy was performed (phosphorus was 5.7 mg/dl, information regarding parathyroid hormone is not available). At this age the diagnosis of an autoimmune polyendocrine syndrome was presumed, given the association with hypocalcemia due to hypoparathyroidism and the presence of antiparietal cell antibodies. It was only in 2016 when a clinical suspicion of a genetic cause for his complex medical history was made, and the diagnosis of a 22q11.2 syndrome was made. Treatment with L-thyroxine, calcitriol and calcium carbonate are well tolerated, but patient needs constant surveillance for this treatment. Our third patient is a 12-year-old male born at 40 weeks of pregnancy. One month after birth he was hospitalized due to a viral gastroenteritis and bronchiolitis. He has a history of repetitive upper respiratory infections and retarded psychomotor development, there is no failure to thrive. At one year of age, he was again hospitalized because of convulsions, which were attributed to a hypocalcemia of 1.62 mmol/l (normal range 2.19–2.64 mmol/l) due to hypoparathyroidism (parathyroid hormone at presentation was 7.3 ng/l, normal range between 15 and 65 ng/l). Phosphate was elevated (2.55 mmol/l, normal range between 1.07 and 1.74 mmol/l). The diagnosis of congenital hypoparathyroidism was made and genetic testing confirmed the clinical suspicion of a 22q11.2 deletion syndrome. Treatment with calcitriol and calcium carbonate was started. No other episodes of seizures followed under this treatment. Our aim is to emphasize the detection of development of hypocalcemia throughout the lifetime of patients with this syndrome, the importance of an early recognition and a multidisciplinary follow-up.

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