BTK, CHD7, FGF8, FGFR1, FOXA2, GH1, GHR, GHRHR, GHSR, GLI2, GLI3, GNRHR, HESX1, IGSF1, LHX3, LHX4, OTX2, PITX2, PNPLA6, POU1F1, PROKR2, PROP1, SOX2, SOX3 andTBX19
Combined pituitary hormone deficiency (CPHD) is defined as the impaired production of anterior pituitary hormones affecting at least two anterior pituitary hormone lineages. A shortage of these hormones may affect the development of many parts of the body, leading to a variable clinical presentation. This is dependent on the on the age at diagnosis and the type and severity of deficiencies. Clinical features may include growth retardation, hypothyroidism, impaired sexual development and infertility. Many cases are idiopathic.
Variants within genes encoding for the transcription factors that act at different stages of pituitary development have been shown to result in unique patterns of hormonal deficiencies reflecting their differential expression during organogenesis (Pfaffle et al. 2013 J Clin Endocrinol Metab 93(3):1062-1071). PROP1, POU1F1, HESX1, LHX3 and LHX4 variants are found in approximately 52% of patients with familial CPHD and 13% of all reported cases (Reynaud et al. 2006 J Clin Endocrinol Metab 91(9):3329-3336).
NHSE test directory code: R159 Pituitary hormone deficiency. Testing criteria can be found on this webpage: https://www.england.nhs.uk/publication/national-genomic-test-directories/.
The laboratory participates in the European Molecular Genetics Quality Network (EMQN) sequencing scheme.