McCune Albright syndrome and bilateral adrenal hyperplasia: the GNAS mutation may only be present in adrenal tissue

Abstract

Objective: Corticotropin (ACTH)-independent hypercortisolism due to bilateral adrenocortical hyperplasia (BAH) in infancy is an extremely rare condition that is often caused by McCune Albright syndrome (MAS). MAS is caused by an activating mutation of the GNAS gene which leads to increased cyclic (c) adenosine monophosphate (AMP) signaling. Most forms of BAH are linked to increased cAMP signaling. We report the case of an infant with MAS who had BAH.

Methods: Genomic DNA fragments from blood and adrenal tissue encompassing regions (exons 8 and 9) with the hot spot activating missense GNAS mutations were amplified by classical bidirectional Sanger sequencing.

Results: The infant was found to carry the most common GNAS mutation, in exon 8 (c.602G >A, p. R201H), only in her adrenocortical tissue, despite extensive skin and other findings.

Conclusions: We conclude that infants with MAS, despite absence of the GNAS activating mutation in blood, may still have significant clinical findings, including ACTH-independent hypercortisolism. Molecular confirmation of the diagnosis should be sought at the tissue level in these patients.

Trial registration: ClinicalTrials.gov NCT00005927.

Conflict of interest statement

CONFLICT OF INTEREST

The authors declare that there is no conflict of interest.

Figures

Figure 1.

A. Skin pigmentations with café-au-lait spots; B. X ray with fibrous dysplasia of multiple ribs; C. Nonspecific signal focal alteration in the left thalamus and stripe signal changes in the dorsal brainstem and pons.

Figure 2.

Electropherograms showing the analysis of the GNAS gene (exon 8, Reference Sequence: NM_000516). A. Blood sample: normal sequence from germline DNA; B. Adrenal tissue: heterozygous substitution of guanine to adenine in the codon 602 of the GNAS gene (c.602G>A; rs121913495). *mutation position.