RETT Syndrome With Proven MECP2 Mutation Clinical Trial
Official title:
Osteoporosis in RETT Syndrome. Understanding the Mechanisms and Identification of Biomarkers.
Based on our clinical observations, many girls with RETT syndrome, a severe
neuro-developmental encephalopathy, suffer from osteoporosis which can appear at a very early
age (before age 10) and can lead to fractures, pain and a limitation in mobility. Few
epidemiological studies have estimated the frequency of osteoporosis in girls with RETT
syndrome and showed that they are more exposed then children with other neuro-developmental
diseases with a same degree of neurological handicap. However, the mechanisms that lead to
early osteoporosis in RETT syndrome remain unknown. Mutations in the MECP2 gene are found in
95% of RETT patients and preliminary experimental studies have shown that this can lead to
abnormal expression of the gene that codes for osteoprotegerin, a protein implicated in bone
remodelling by interacting with RANK-ligand.
In order to identify risk factors of osteoporosis in RETT syndrome and to understand the
pathophysiological mechanisms the study protocol includes:
1. Clinical evaluation of bone health (history of bone fractures, pain, nutritional status,
pubertal stage, daily caloric/calcium intake, anti-epileptic drugs, walking ability,
vitamin D satus)
2. evaluation of the mineral density at the lumber spine using DEXA
3. measuring concentrations of osteoprotegerin and RANK-ligand
Based on our clinical observations, many girls with RETT syndrome, a severe
neuro-developmental encephalopathy, suffer from osteoporosis which can appear at a very early
age (before age 10) and can lead to fractures, pain and a limitation in mobility. Few
epidemiological studies have estimated the frequency of osteoporosis in girls with RETT
syndrome and showed that they are more exposed to osteoporosis then children with other
neuro-developmental diseases with a same degree of neurological handicap. However, the
mechanisms that lead to early osteoporosis in RETT syndrome remain unknown.
Mutations in the MECP2 gene are found in 95% of RETT patients. Preliminary experimental
studies on the transcriptional consequences of MECP2 mutations showed that the expression of
13 genes were significantly dysregulated and one of them is the gene that codes for
osteoprotegerin, a soluble receptor that binds to RANK-ligand. RANK-ligand is an osteoclastic
differentiation factor expressed by osteoblasts.
In order to identify risk factors of osteoporosis in RETT syndrome and to understand the
pathophysiological mechanisms the study protocol includes:
1. Clinical evaluation of bone health (history of bone fractures, pain, nutritional status,
pubertal stage, daily caloric/calcium intake, anti-epileptic drugs, walking ability,
vitamin D status)
2. evaluation of the mineral density at the lumber spine using DEXA
3. measuring concentrations of osteoprotegerin and RANK-ligand
;