The spectrum of parathyroid gland dysfunction associated with the microdeletion 22q11

Abstract

Objective: Clinical features associated with microdeletion of chromosome 22q11 (del(22)(q11)) are highly variable. Increased awareness of this condition is needed among specialists such as endocrinologists to reduce diagnostic delay and improve clinical care. The purpose of this study was to describe the phenotype of patients with del(22)(q11), focusing on parathyroid gland dysfunction. Design and methods: Charts of 19 patients, including one kindred of three, known to have del (22)(q11) diagnosed by fluorescence in situ hybridization (FISH) were reviewed from the register of the department of Medical Genetics. Major clinical features including hypoparathyroidism phenotype were collected. Results: Parathyroid dysfunction was present in 8 out of 16 patients (50%). Six patients were diagnosed with overt hypoparathyroidism. Hypocalcemia manifested as laryngeal stridor within the first days of life (nZ3), seizures in infancy (nZ1) and adolescence (nZ2). The connection between hypoparathyroidism and diagnosis of del(22)(q11) was belated at the median age of 18 years. One patient had presented with transient neonatal hypoparathyroidism, and one patient had latent hypoparathyroidism. Within the kindred family, the phenotype variability including that of parathyroid dysfunction was as marked as between unrelated individuals. Standard karyotype failed to detect the deletion in 15 out of 19 cases. Conclusions: Abnormal parathyroid function in the del(22)(q11) ranges from severe neonatal hypocalcemia to latent hypoparathyroidism. Del(22)(q11) should be considered as a potential cause of hypocalcemia even in young adult. When suspected, the diagnosis requires investigation by FISH. Furthermore, long-term calcemia follow-up is needed in normocalcemic patients with del(22)(q11) because of the possible evolution to hypocalcemic hypoparathyroidism.European Journal of Endocrinology 155 47-52

Velo‐cardio‐facial syndrome: 30 Years of study

“…A large number of other structural anomalies have been reported in association with VCFS including ocular anomalies [Mansour et al, 1987], cranial anomalies [Arvystas and Shprintzen, 1984], limb anomalies [Ming et al, 1998], meningomyelocele [Nickel et al, 1994], anal anomalies [Worthington et al, 1997], platelet anomalies [Van Geet et al, 1998], brain anomalies [Worthington et al, 2000;Eliez et al, 2001;Kates et al, 2004;Antshel et al, 2005;Kates et al, 2006a and b;Schaer et al, 2006;Debbane et al, 2006], renal anomalies [Czarnecki et al, 1998;Shprintzen, 2005b], spine and skeletal anomalies [Ricchetti et al, 2004], thyroid disorders [Kawame et al, 2001], and hypoparathyroidism [Hieronimus et al, 2006]. In all, over 180 separate anomalies or developmental sequences have been reported in association with VCFS covering nearly every organ and system [Robin and Shprintzen, 2005;Shprintzen, 2005b;Shprintzen, 2000a;VCFS Educational Foundation, 2007].…”

Syndromes of the First and Second Branchial Arches, Part 2: Syndromes

“…58 Although the absence of parathyroid gland function is rare, parathyroid dysfunction is present in approximately half of patients with VCFS. 59 The second emergent situation is related to infections from deficiencies with the T-cellϪ mediated response of the immune system due to an absent or hypoplastic thymus. Immunologic evaluation is critical in affected children to identify those that may require either lymphocyte or thymus transplantation.…”

Bone density and metabolism in subjects with microdeletion of chromosome 22q11 (del22q11)

“…Commonly, however, with an increase in dietary calcium intake, the remaining parathyroid activity supplies sufficient PTH to meet metabolic demands, even if a recurrence of hypoparathyroidism may be precipitated during the periods of increased metabolic demand (18). Therefore, a long-term follow-up should be given to 22q11DS patients with normocalcaemia because of the potential for evolution to hypocalcaemic hypoparathyroidism (22).…”