Alternative titles; symbols
SNOMEDCT: 237683004; ORPHA: 90695; DO: 0111779;
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
Gene/Locus |
Gene/Locus MIM number |
|---|---|---|---|---|---|---|
| Xq27.1 | Panhypopituitarism, X-linked | 312000 | X-linked | 3 | SOX3 | 313430 |
A number sign (#) is used with this entry because some cases of X-linked panhypopituitarism are associated with duplications in the SOX3 gene (313430).
X-linked mental retardation with pituitary deficiency (300123) is an allelic disorder with an overlapping phenotype.
See also X-linked hypogammaglobulinemia and isolated growth hormone deficiency (307200) and autosomal panhypopituitarism (262600).
Zipf et al. (1977) reported 2 pre-pubertal males with X-linked hypopituitarism and gonadotropin deficiency. Mental deficiency was not reported.
Woods et al. (2005) reported 2 Finnish male maternal half sibs with X-linked hypopituitarism. Clinical features included neonatal hypoglycemia and growth hormone deficiency in addition to variable deficiencies of other pituitary hormones. Brain MRI of both boys showed hypoplasia of the anterior pituitary with hypoplasia or absence of the lower half of the infundibulum. Both had normal psychomotor development, although 1 was hyperactive. Woods et al. (2005) reported a second family in which 4 male sibs had panhypopituitarism. The family was consanguineous and of Qatari origin. Brain MRI in 3 of the patients showed a small anterior pituitary gland and absent or attenuated infundibulum. All had normal neurodevelopment.
Using array comparative genomic hybridization (array CGH) in 3 families with X-linked hypopituitarism, including the family reported by Zipf et al. (1977), Solomon et al. (2004) identified 3 different Xq26-q27 duplications, which together refined the critical region to a 3.9-Mb interval at Xq27.2-q27.3, including the SOX3 gene. None of the affected individuals had mental retardation, although some had learning difficulties. Solomon et al. (2007) reported that they were unable to replicate the findings of an Xq26-q27 duplication in 3 families studied by Solomon et al. (2004), including the family reported by Zipf et al. (1977).
In affected members of 2 unrelated families with X-linked panhypopituitarism, Woods et al. (2005) identified duplications in the SOX3 gene (313430.0002 and 313430.0003, respectively). The findings implicated SOX3 in the development of the midline forebrain structures. None of the patients had mental retardation.
Solomon, N. M., Ross, S. A., Forrest, S. M., Thomas, P. Q., Morgan, T., Belsky, J. L., Hol, F. A., Karnes, P. S., Hopwood, N. J., Myers, S. E., Tan, A. S., Warne, G. L. Array comparative genomic hybridisation analysis of boys with X-linked hypopituitarism identifies a 3.9 Mb duplicated critical region at Xq27 containing SOX3. (Letter) J. Med. Genet. 44: e75, 2007. Note: Electronic Article. [PubMed: 17400794] [Full Text: https://doi.org/10.1136/jmg.2007.049049]
Solomon, N. M., Ross, S. A., Morgan, T., Belsky, J. L., Hol, F. A., Karnes, P. S., Hopwood, N. J., Myers, S. E., Tan, A. S., Warne, G. L., Forrest, S. M., Thomas, P. Q. Array comparative genomic hybridisation analysis of boys with X linked hypopituitarism identifies a 3.9 Mb duplicated critical region at Xq27 containing SOX3. J. Med. Genet. 41: 669-678, 2004. [PubMed: 15342697] [Full Text: https://doi.org/10.1136/jmg.2003.016949]
Woods, K. S., Cundall, M., Turton, J., Rizotti, K., Mehta, A., Palmer, R., Wong, J., Chong, W. K., Al-Zyoud, M., El-Ali, M., Otonkoski, T., Martinez-Barbera, J.-P., Thomas, P. Q., Robinson, I. C., Lovell-Badge, R., Woodward, K. J., Dattani, M. T. Over- and underdosage of SOX3 is associated with infundibular hypoplasia and hypopituitarism. Am. J. Hum. Genet. 76: 833-849, 2005. [PubMed: 15800844] [Full Text: https://doi.org/10.1086/430134]
Zipf, W. B., Kelch, R. P., Bacon, G. E. Variable X-linked recessive hypopituitarism with evidence of gonadotropin deficiency in two pre-pubertal males. Clin. Genet. 11: 249-254, 1977. [PubMed: 192503] [Full Text: https://doi.org/10.1111/j.1399-0004.1977.tb01309.x]