During the last decade, some reports documented the existence of patients with POH showing additional features characteristic of AHO such as short stature and brachydactyly, previously thought to occur only in other GNAS-associated disorders.
The segregation of brachydactyly with PHP 1b in this family indicates that an imprinting defect in GNAS can lead to growth plate defects, including brachydactyly and Madelung deformity.
In this report, we describe two unrelated patients with mental retardation and brachydactyly E classified as patients suffering from Albright hereditary osteodystrophy-like (AHO-like) syndrome.
Further studies in PHP-Ia subjects without GNAS mutations and in other brachydactyly syndromes will determine whether the pattern described is also specific.
Functional polymorphisms in the paternally expressed XLalphas and its cofactor ALEX decrease their mutual interaction and enhance receptor-mediated cAMP formation.