Osteoporosis in RETT Syndrome
Condition: RETT Syndrome With Proven MECP2 Mutation
MeSH terms: Osteoporosis; Rett Syndrome; Syndrome
Study type: Interventional

Summary: 
      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
    

Detailed description: 
      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
    

Intervention name(s): biological markers and evaluation of the mineral density at the lumber spine using DEXA
Intervention type(s): Other
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Diagnostic
Keywords: RETT syndrome; MECP2; Osteoporosis; RANK-ligand; osteoprotegerin