Panhypopituitarism, X-Linked

Alternative Names

  • PHPX

Associated Genes

SRY-BOX 3
Back to search Result
WHO-ICD-10 version:2010

Endocrine, nutritional and metabolic diseases

Disorders of other endocrine glands

OMIM Number

312000

Mode of Inheritance

X-linked

Gene Map Locus

Xq26.3, Xq27.2-q27.3

Description

X-linked forms of hypopituitarism are characterized by concomitant deficiencies in several of the anterior pituitary hormone lineages. This disease only affects men, who display profound growth hormone deficiency from birth, and most of whom also have deficiencies in other anterior pituitary hormones. In some cases, patients are deficient in all anterior pituitary hormones (panhypopituitarism). Without treatment, the main displayed symptoms include growth retardation leading to dwarfism (GH deficiency). Mild non-specific mental retardation is also a feature of most patients with X linked hypopituitarism.

Molecular Genetics

Duplications of Xq26-27 have been implicated in the etiology of X-linked hypopituitarism associated with mental retardation. This region contains SOX3 gene. Additionally, an expansion of a polyalanine tract (by 11 alanines) within this gene (Xq27.1) has been reported in patients with growth hormone deficiency and variable learning difficulties. SOX3 is a transcription factor which is implicated in the control of nervous system development and is considered to be one of the earliest neural markers.

Epidemiology in the Arab World

View Map

Other Reports

Qatar

Woods et al. (2005) described four male siblings affected with panhypopituitarism. They were born to first-cousin consanguineous Qatari parents. These affected siblings (first, second, and third child) first presented with the short stature before age of five. Their heterozygous mother is of normal height. The first patient had two small testes lying in the scrotum, whereas the second and third patients had a micropenis, with bilaterally undescended testes. The three patients had low levels of GH (1.7, 0.7, 0.7 ng/ml, respectively, normal ranges: GH>6.7 ng/ml), FT4 (0.5, 0.7, 0.5 ng/dl, respectively; normal ranges: 0.9-1.9 ng/dl), TSH (0.08, 3.3, 2.8 microU/ml, respectively; normal ranges: 0.5-6.0 microU/ml), and cortisol (2.0, 3.9, 3.2 respectively; normal ranges: peak cortisol > 19.8 micro/dl). The fourth sibling presented at age 9 years with deficiencies of GH (peak GH 2.8 ng/ml) and basal cortisol (12.1 micro/dl) concentrations. Brain MRI in the last three patients showed a small anterior pituitary gland and absent or attenuated infundibulum. None of the patients had mental retardation and all of them had normal neurodevelopment. Pubertal induction was required in all patients by using depot preparation of testosterone (Sustanon), because the concentrations of gonadotrophin (LH, FSH) were undetectable or low. The patients were continuously treated with Sustanon, rhGH, thyroxine, and hydrocortisone. The heights of the first, second, and fourth patients were 162.5 cm (-1.9 SDS), 159 cm (-1.2 SDS), and 138 cm (-1.8 SDS), and they weighed 66.5 kg (+0.2 SDS), 61.4 kg (+0.6 SDS), and 59.8 kg (+1.9 SDS), respectively. In the third patient, the height SDS and weight SDS were -0.1 and +1.5, respectively. These measurements were taken at age above or equal to 12.5 years in all patients. At the molecular level, Woods et al. (2005) identified a novel seven-alanine expansion (from 15 to 22 alanine residues) within a polyalanine tract in the SOX3 gene, leading to reduced transcriptional activity and impaired nuclear localization of the mutant protein. The first three patient were found to be homozygous for this mutation (DNA from the fourth patient is unavailable), whereas the mother of these four children was heterozygous for the same mutation and did not exhibit significantly skewed X inactivation in DNA extracted from pheripheral blood.

© CAGS 2021. All rights reserved.