Chapter 56 - Genetic regulation of parathyroid gland development

Abstract

Congenital anomalies of parathyroid gland development, which lead to hypoparathyroidism, are common and occur in more than 1 in 4000 births. The four human parathyroid glands develop from transient bilateral outpocketings of the pharyngeal endoderm, which are referred to as the pharyngeal pouches. There are four pairs of pharyngeal pouches; the superior parathyroid glands develop from the fourth pharyngeal pouches, which are the most caudal, while the inferior parathyroid glands together with the thymus develop from the third pharyngeal pouches. The pharyngeal pouches together with the branchial arches and grooves form the branchial apparatus that gives rise to a number of structures that include the face, jaws, oral cavity, neck, pharynx, larynx, ear, aortic arch, tonsils, thyroid, parathyroids, thymus, ultimobranchial body that results in calcitonin-producing cells, carotid glomus, and the epibranchial placodes that contribute to the facial, glossopharyngeal, and vagus nerves. Thus, developmental abnormalities of the branchial apparatus and pharyngeal pouches may lead to hypoparathyroidism that may be part of a complex congenital defect, as for example in the DiGeorge syndrome or a solitary endocrinopathy which is called isolated or idiopathic hypoparathyroidism. In addition, hypoparathyroidism may occur in association with other developmental anomalies involving dysmorphic features, sensorineural deafness, lymphoedema, nephropathy, and growth retardation. The molecular genetic basis for such forms of hypoparathyroidism has been investigated and this has helped to elucidate further the mechanisms involved in the genetic regulation of parathyroid gland development. This chapter will focus on those forms of hypoparathyroidism that often present in early life, as these are likely to be associated with parathyroid gland agenesis or hypoplasia, or a congenital deficiency of parathyroid hormone (PTH), or an early destruction of the parathyroids. The hypoparathyroidism in these forms is characterized by hypocalcemia and hyperphosphatemia due to a deficiency in PTH secretion.