McCune-Albright syndrome accelerates puberty and affects bones

Syndrome McCune-Albright This genetic disease which was described in 1937 and causes precocious puberty (especially in girls) with café-au-lait spots on the skin, and also affects the bones (fibrous dysplasia, in which abnormal fibrous tissue replaces healthy bone and can weaken it, causing pain, fractures or deformities).

This triad of symptoms which may be present in whole or in part; That is, not all three must always occur, but sometimes only one, sometimes two, or all three at the same time.

This was stated in an interview with Infosalus by a professor of pediatrics at the Autonomous University of Madrid Dr. Jesus ArgenteMember of the Spanish Society of Pediatric Endocrinology (SEEP) and Head of the Pediatrics and Pediatric Endocrinology Service at the Children’s Hospital of the Niño Jesus University in Madrid.

The specialist emphasizes that “this is not common in our society,” while also emphasizing that this is rare genetic disease“Its incidence and prevalence are difficult to establish and it is understudied internationally, making its epidemiological investigation very challenging.”

Today we know that this syndrome is caused by the existence mutations in the GNAS genewhich occur during pregnancy and affect only some cells of the body (somatic mosaicism), the pediatrician describes. “Because of this mosaic picture,” continues Dr. Argente, “patients with this syndrome have a wide spectrum of clinical manifestations due to the variable tissue distribution of the GNAS mutation.”

It usually makes its debut at any point in childhood, heads the pediatrics and pediatric endocrinology department at the Niño Jesus University Children’s Hospital in Madrid, and notes that given presence of precocious pubertyAt the time of diagnosis of the syndrome, its central origin (hypothalamic-pituitary) was excluded, which indicates its peripheral origin (due to vegetative activation of the ovaries).

In particular, precocious puberty is diagnosed before the age of 8 in girls and before the age of 9 in boys; the main signs of this, depending on gender, are thelarche or development of the mammary glands in girls; and an increase in the volume of the testicles (more than 4 milliliters) in boys.

“If there is already spots coffee with milk and/or osteofibrous dysplasiaTo establish a diagnosis, it is necessary to conduct a genetic study. However, it is necessary to take into account that molecular diagnostics in peripheral blood is limited, mainly due to the mosaic distribution of activating mutations, which are often not detected in peripheral blood,” the doctor emphasizes.

Thus, he protects need that it is a rare disease be diagnosed at an early stage: “Although traditionally described as a classic triad, it is now accepted that some patients exhibit only one or two classic symptoms.”

However, this process is not so simple, since molecular diagnosis in peripheral blood is often negative, as Argente points out. “However, tissue DNA testing gives a positive result in more than 90% of clinical cases, although, naturally, the more invasive method makes it more difficult to carry out. Currently, there are high hopes for very sensitive methodssuch as the so-called ddPCR (droplet digital PCR) to make molecular diagnostics of peripheral blood more feasible,” the expert emphasizes.

However, this pediatrician regrets that at present there is no effective clinical treatment is generally accepted to stop the progression and regression of the syndrome, and advises that this should always be carried out under the guidance of a multidisciplinary team of specialists.

“To control precocious puberty, treatment has been heterogeneous: medroxyprogesterone acetate, tamoxifen, ketoconazole have been used; and more recently in girls aromatase inhibitors“More than 50% of patients may develop central precocious puberty, which can be treated with GnRH analogues,” he notes.

On the other hand, a member of the Spanish Society of Pediatric Endocrinology specifies that bisphosphonates (pamidronate or zoledronic acid) are used in the treatment of fibrous dysplasia. “The presence of other endocrinological complications Less often, they require specific treatment (hyperthyroidism, Cushing’s syndrome, or excess growth hormone),” the doctor concludes.