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.