Table 2.

Genetic syndromes associated with primary hypoparathyroidism

Genetic defect	Syndrome	Clinical manifestations	Parathyroid pathology
GCM2 (6p23-24) SOX3 (insertion-deletion 2p25.3 and Xq26-27)	Isolated parathyroid aplasia	Primary hypoparathyroidism Infantile hypocalcemic seizures	Agenesis of parathyroid glands
TBX1(22q11.2) NEBL (10p13)	DiGeorge Syndrome (DGS, type 1) DGS, type 2	Thymic aplasia, T-cell defects, conotruncal anomalies, cleft palate, dysmorphic facies	Hypoalcemia due to parathyroid hypoplasia
CHD7 (8q12.2) SEMA3E (7q21.11)	CHARGE syndrome	Coloboma, heart defects, choanal atresia, retarded growth, genital hypoplasia, ear anomalies	Hypocalcemia due to parathyroid hypoplasia
GATA3 haploinsufficiency	HDR/Barakat syndrome	Transient to severe neonatal hypocalcemia, deafness, renal dysplasia	Hypocalcemia due to parathyroid hypoplasia
TBCE (1q42-43)	HRD/Sanjad-Sakati Syndrome (Arabic descent mostly) KCS/Kenny-Caffey syndrome	Hypoparathyroidism, retardation, dysmorphism	Hypocalcemia due to parathyroid hypoplasia
Mitochondrial disease (Kearns-Sayre, Pearson Marrow-pancreas syndromes, MELAS, LCHAD, MCADD)		Various manifestations based on the specific disease	Hypoparathyroidism
PTH (11p15.3-p15.1)	Isolated familial hypoparathyroidism	Hypocalcemia	Hypocalcemia due to defective PTH
CASR (ADH1) (3q13.3-q21.1) GNA11 (ADH2) (19p13)	Autosomal dominant hypocalcemia, types 1 and 2	Neonatal to adult presentation of hypocalcemia (increased urinary calcium excretion, decreased PTH synthesis)	Increased sensitivity of the calcium sensing receptor to extracellular ionized calcium
AIRE (21q22.3)	Autoimmune polyendrocrinopathy candidiasis ectodermal dysplasia (APECED)	Mucocutaneous candidiasis, hypoparathyroidism, adrenal insufficiency, endocrinopathies, hepatitis, vitiligo, alopecia, nail/dental dystrophy	Hypocalcemia due to autoimmune destruction of parathyroid glands