ESPE Abstracts

Objective: to assess the prevalence of endocrinopathies in a pediatric population of Rett syndrome (RTT) patients.

Design: retrospective observational double center study.

Methods: 51 caucasian patients (47 girls, 4 boy) with genetically confirmed diagnosis of RTT were enrolled (mean age: 9.65±5.9 years, range: 1-18 years). The patients were referred from the Rett Center of two Italian Hospitals 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 post pubertal girls. Midline defects were excluded by brain MRI.

Results: MeCP2 deletions were detected in 38 patients (74.5%) and CDKL5 deletions in 11 patients (21.6%). Only 2 patients exhibited mutations of FOXG1. Overall, 40 patients were treated with anticonvulsant drugs.

Short stature: 24 patients (47%) had a height <-2 standard deviation score SDs (mean SDs -3.18, range: - 8.26/-2.0) and below targets height. Of these, 7 girls also had BMI<-2 SDs and 4 had thyroid dysfunction. Celiac disease and GH deficit were excluded.

Malnutrition: 13 patients (25.5%) had severe underweight (mean BMI SDs -3.79, range: -2.54/-8.19 SDs), in absence of other chronic diseases.

Obesity: 10 patients (19.6%) had BMI>2 SDs (mean BMI +2.35 SDs, range: +2.0/+2.98 SDs), 2 of them with basal hyperinsulinemia.

Gonadal function: among the 26 post-pubertal girls, 4 had a history of precocious puberty and one premature isolated pubarche. 12/26 (46.1%) patients claimed menstrual cycle abnormalities (secondary amenorrhea and oligomenorrhea); all of them had concurrent weight disorders (7 were overweight or obese and 5 underweight). Thyroid abnormalities (5 patients, 9.8%): central hypothyroidism (1 patient), subclinical hypothyroidism (1 patient), Hashimoto’s thyroiditis in euthyroidism (1 patient), and thyroid nodules (2 patients).

Hyperprolactinemia: 7 patients (13.7%) exhibited high prolactin blood levels, with occurrence of galactorrhea in one case, during anticonvulsant therapy.

Bone health: 11 patients (21.6%) had vitamin D deficiency. DEXA highlighted osteopenia in 4 patients and osteoporosis in 6 patients (two of them requiring bisphosphonates). In the entire study population, endocrinopathies were significantly more frequent in patients with MECP2 deletions (P=0.0005).

Conclusions: in our RTT pediatric population, short stature was the most frequent endocrinological report, followed by menstrual cycle abnormalities and weight disorders. Interestingly, patients with MECP2 deletions seemed to be at higher risk for developing endocrinopathies. Therefore, in the context of a multidisciplinary approach, endocrinological evaluation should be recommended in RTT patients.