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macroorchidism in McCune-Albright syndrome
Wednesday 21 April 2010
McCune-Albright syndrome (MAS), usually presenting with polyostotic bone dysplasia, café-au-lait skin lesions and sexual precocity, results from a somatic activating mutation of the GNAS1 gene, which encodes the Gs-alpha protein involved in signalling of several G-protein-coupled receptors.
The clinical spectrum depends on tissue distribution of mutant-bearing cells. Sexual precocity has been ascribed to the occurrence of a mutant GNAS1 allele in the gonadal anlage, from which all somatic cells of the differentiated gonads arise.
Peripheral precocious puberty (PPP) in boys with MAS is generally associated with bilateral testicular enlargement, but monolateral macroorchidism may also be seen. (16789625)
Synopsis
Sertoli cell hyperactivity.
No signs of hyperandrogenism.
Testicular microlithiasis (15520771)
Sexual precocity is rare in MAS males while isolated testicular enlargement is frequently observed.
Gs-alpha (GNAS1) is functional in both Sertoli and Leydig cells.
The mutant GNAS1 allele can be present only in Sertoli cells, resulting in isolated Sertoli cell hyperfunction, evidenced by increased AMH expression and cell hyperplasia leading to prepubertal macro-orchidism, with no signs of Leydig cell activation.
The different early embryologic origin of precursors contributing to Sertoli and Leydig cell lineages may underlie the differential existence of the mutated GNAS1 gene.
Lack of occurrence of the mutation in Leydig cells may explain why sexual precocity is rarely observed in boys with MAS.
See also
unilateral enlargement of the testis in childhood
R201H-GNAS1 mutations
References
Unexpected mosaicism of R201H-GNAS1 mutant-bearing cells in the testes underlie macro-orchidism without sexual precocity in McCune-Albright syndrome. Rey RA, Venara M, Coutant R, Trabut JB, Rouleau S, Lahlou N, Sultan C, Limal JM, Picard JY, Lumbroso S. Hum Mol Genet. 2006 Dec 15;15(24):3538-43. PMID: 17101633 (Free)
Clinical presentation of McCune-Albright syndrome in males. Wasniewska M, Matarazzo P, Weber G, Russo G, Zampolli M, Salzano G, Zirilli G, Bertelloni S; Italian Study Group for Alterations of Gs alpha Protein Function. J Pediatr Endocrinol Metab. 2006 May;19 Suppl 2:619-22. PMID: 16789625
