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


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 (n = 3), seizures in infancy (n = 1) and adolescence (n = 2). 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.
Hiéronimus
Sylvie
S
Department of Endocrinology and Reproductive Medecine, Nice University Hospital, BP 3079, 06202 Nice cedex 3, France. hieronimus.s@chu-nice.fr
Bec-Roche
Magali
M
Pedeutour
Florence
F
Lambert
Jean Claude
JC
Wagner-Malher
Kathy
K
Mas
Jean Christophe
JC
Sadoul
Jean Louis
JL
Fénichel
Patrick
P
D000293:Adolescent; D000328:Adult; D002892:Chromosomes, Human, Pair 22 / Q000235:genetics*; D005260:Female; D017353:Gene Deletion; D006801:Humans; D006996:Hypocalcemia / Q000097:blood / Q000209:etiology; D007011:Hypoparathyroidism / Q000209:etiology / Q000235:genetics; D017404:In Situ Hybridization, Fluorescence; D007621:Karyotyping; D008297:Male; D008875:Middle Aged; D010279:Parathyroid Diseases / Q000097:blood / Q000235:genetics* / Q000503:physiopathology; D010281:Parathyroid Hormone / Q000097:blood; D010641:Phenotype; D012189:Retrospective Studies; D012640:Seizures / Q000209:etiology / Q000235:genetics
D010281:Parathyroid Hormone