Unusual Phenotypical Variations in a Boy with McCune-Albright Syndrome

Abstract

Background: McCune-Albright syndrome (MAS) typically comprises the constellation of polyostotic fibrous dysplasia, café-au-lait spots, and associated endocrinopathies including gonadotropin-independent precocious puberty, excessive growth hormone production and gigantism, hyperthyroidism, and hyperparathyroidism. Objective: We report the unique case of a boy with the diagnostic criteria of MAS accompanied by atypical short stature and macroorchidism without precocious puberty. Patient: An 8.4-year-old prepubertal boy presented with a history of recurrent bone fractures, multiple café-au-lait spots, bilateral macroorchidism, and short stature. X-ray of the extremities was consistent with polyostotic fibrous dysplasia. Serum inhibin B (IB) and anti-müllerian hormone (AMH) were elevated; testosterone, LH, and FSH were normal for age. Results: PCR-based DNA analysis of bone tissue revealed a substitution of arginine for cysteine at position 201 in the G_sα protein resulting in activation of the G_sα subunit. Conclusions: We report a second case of MAS associated with macroorchidism. In this case, isolated Sertoli cell hyperfunction was also associated with microlithiasis and was not associated with peripheral precocious puberty. Short stature not associated with GH-IGF-1 axis abnormality was a second anomalous finding in this case. Our experience suggests that the phenotypic variation in MAS is wider than previously described.

Anti-Müllerian hormone as a marker of steroid and gonadotropin action in the testis of children and adolescents with disorders of the gonadal axis

“…Although precocious puberty is one of the classic components of McCune-Albright syndrome, macro-orchidism in the absence of androgen-dependent secondary sexual characteristics has also been reported in boys [70, 71]. In some cases, increased Sertoli cell proliferation was detected by the presence of small hyperechogenic foci in ultrasound imaging [72].…”

SOX9 and SF1 are involved in cyclic AMP-mediated upregulation of anti-Müllerian gene expression in the testicular prepubertal Sertoli cell line SMAT1

“…Accordingly, serum AMH is lower than expected in rodents with an inactivation of the FSH ␤-subunit gene (2) as well as in patients with congenital hypogonadotropic hypogonadism, a condition characterized by extremely low pituitary FSH secretion (9,67), and increases in response to FSH administration in both rodents (2) and humans (9,66). On the other hand, AMH is abnormally high in prepubertal boys with an activating mutation of the G s ␣ protein involved in FSH receptor signaling in Sertoli cells (14,34,47) and in rams overexpressing the FSH receptor (51). These observations prompted us to study a potential regulation of testicular AMH production by FSH in late fetal life and after birth.…”

Fetal ovarian cysts: an early manifestation of McCune–Albright syndrome?

“…The disorder is related to an autonomous hyperfunction of the endocrine cells because of a post‐zygotic constitutively activating mutation in the gene for the α subunit of the G protein ( GNAS ) . The mutation is nearly always a substitution of the residue arginine at position 201 by histidine or cysteine, as reported by many authors including our group . In rare cases, arginine is replaced by serine, glycine, or leucine …”