ESPE Abstracts

Background: systematic data about endocrinopathies in Rett syndrome (RTT) patients are still scarce and not univocal.

Objective: to assess the prevalence of endocrinopathies in a pediatric population of RTT patients.

Design: retrospective observational single center study.

Methods: 29 caucasian patients (28 girls,1 boy) with genetically confirmed diagnosis of RTT were enrolled (mean age:13.2±5.4 years, range:3.3-18 years). The patients were referred from the Rett Center of our Hospital for endocrinological evaluation. All the patients underwent clinical assessment (height, weight, BMI, pubertal staging) and hormonal workup. Thyroid ultrasonography (US) was routinely performed. Pelvic US and bone densitometry (DEXA) were performed in postpubertal girls. Midline defects were excluded by brain MRI.

Results: 27 patients (93.1%) presented MeCP2 deletions, with R255X and R306C being the most prevalent. Only 2 patients exhibited less common genotypes, respectively CDKL5 and FOXG1 deletions. Overall, 24 patients were treated with anticonvulsant drugs.

Short stature: 16 patients (55.2%) had a height <-2 standard deviation score SDs (median -2.88 SDs, range:--2.0/-4.33) and below target height. Of these, 6 girls also had BMI<-2 SDs and 5 had thyroid dysfunction. Celiac disease and GH deficit were excluded.

Malnutrition: 10 patients (34.5%) had severe underweight (median BMI -3.15 SDs, range: -2.5/-8.2SDs), in absence of other chronic diseases.

Obesity: 6 patients (20.7%) had BMI>2 SDs (median BMI +2.39 SDs, range: +2/+2.5 SDs), 2 of them with basal hyperinsulinemia.

Gonadal function: among the 19 post-pubertal girls, 4 had a history of precocious puberty and one premature isolated pubarche. 9/19 (47.4%) patients claimed menstrual cycle abnormalities (secondary amenorrhea and oligomenorrhea); all of them had body weight alteration (5 were overweight and 4 underweight). Thyroid abnormalities (5 patients,17.2%): central hypothyroidism (1 patient), subclinical hypothyroidism (1 patient), Hashimoto’s thyroiditis in euthyroidism (1 patient), and thyroid nodules (2 patients).

Hyperprolactinemia: 6 patients (20.7%) exhibited high prolactin blood levels, with occurrence of galactorrhea in one case, during anticonvulsant therapy.

Bone health: 9 patients (31%) had vitamin D deficiency. DEXA highlighted osteopenia in 4 patients and osteoporosis in 5 patients (one of them requiring biphosfonate). None of the genotypes of our patients was significantly associated to a specific endocrine phenotype.

Conclusions: in our RTT pediatric population, short stature was the most frequent endocrinological report, followed by poor weight gain and menstrual cycle abnormalities. Bone health concerns are relevant in RTT, for both motor impairment and skeletal abnormalities. In the context of a multidisciplinary approach, endocrinological evaluation should be recommended in RTT patients.