Pituitary Hormone Deficiency, Combined, 6

A number sign (#) is used with this entry because combined pituitary hormone deficiency-6 (CPHD6) is caused by heterozygous mutation in the OTX2 gene (600037) on chromosome 14q21.

For discussion of phenotypic and genetic heterogeneity of combined pituitary hormone deficiency, see CPHD1 (613038).

Heterozygous mutation in the OTX2 gene can also cause microphthalmia with associated features, including pituitary dysfunction (see MCOPS5, 610125).

Molecular Genetics

In 19 patients with hypopituitarism, Diaczok et al. (2008) analyzed 8 genes encoding pituitary-specific transcription factors, including HESX1 (601802), LHX3 (600577), LHX4 (602146), OTX2, PITX2 (601542), POU1F1 (173110), PROP1 (601538), and SIX6 (606326), and identified heterozygosity for a missense mutation in the OTX2 gene (600037.0006) in 2 unrelated patients. One was a 6-year-old boy with deficiency of GH, adrenocorticotropic hormone (ACTH), thyroid-stimulating hormone (TSH), luteinizing hormone (LH), and follicle-stimulating hormone (FSH), who on MRI had an ectopic neurohypophysis, along with a hypoplastic adenohypophysis and absent or severely hypoplastic pituitary stalk. The other patient was a 14-year-old girl with deficiency of TSH, ACTH, and GH, in whom MRI at age 2 months showed hypoplasia of the pituitary with a posterior bright spot. Neither patient had midline or optic nerve abnormalities.