Bone Mass in Rett Syndrome: Association with Clinical Parameters and MECP2 Mutations

Shapiro, Jay R.; Bibat, Genila; Hiremath, Girish; Blue, Mary E.; Hundalani, Shilpa G; Yablonski, Theodore; Kantipuly, Aditi; Rohde, Charles A.; Johnston, Michael V.; Naidu, Sakkubai

doi:10.1203/pdr.0b013e3181f2edd2

Cited by 23 publications

(33 citation statements)

References 29 publications

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“…172,173 Fracture risk was four times that of the general female population, and specifically increased in those with p.Arg168* and p.Arg270*mutations (see Fig 2). 173 Several Danish, 174,175 US 176,177 and further Australian studies 178,179 have also investigated which particular bone parameters were most adversely affected and their potential nutritional, 180 (e.g. Vitamin D status) environmental and genetic risk factors.…”

Section: Bone Healthmentioning

confidence: 99%

Clinical and biological progress over 50 years in Rett syndrome

2016

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It is fifty years since Andreas Rett first described Rett syndrome, a disorder now known to be caused by a mutation in the MECP2 gene. A compelling blend of astute clinical observations, clinical and laboratory research has already built our understanding of Rett syndrome and its biological underpinnings. We document the contributions of the early pioneers and describe the evolution of knowledge in terms of diagnostic criteria, clinical variation and the interplay with other Rett-related disorders. We provide a synthesis of what is known about the neurobiology of MeCP2, the lessons from both cell and animal models and how they may inform future clinical trials. With a focus on the core criteria, we examine the relationships that have been demonstrated between genotype and clinical severity. We review what is known about the many comorbidities that occur in this disorder and how genotype may also modify their presentation. We acknowledge the important drivers that are accelerating this research program including the roles of research infrastructure, international collaboration and advocacy groups. Finally, we conclude by highlighting the major milestones since 1966 and what they mean for the day-to-day lives of those with Rett syndrome and their families. Key pointsThere has been an explosion of knowledge about Rett syndrome in relation to its genetic basis, clinical characteristics and their relationships during the fifty years since the disorder was first described by Andreas Rett.Whilst initially the diagnosis of Rett syndrome was based only on clinical criteria, identifying its genetic cause has had a major positive impact on how clinicians diagnose the disorder but also provides new challenges as we enter the era of next generation sequencing.

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Section: Bone Healthmentioning

confidence: 99%

Clinical and biological progress over 50 years in Rett syndrome

2016

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“…However, in general, studies have reported conflicting associations of the effects of physical activity on bone turnover in different populations (37). Also, DXA studies of the association between bone mass and ambulant ability in RTT have shown diverging results (4,6,7,13,38).…”

Section: Rett Syndrome and Low Bone Turnovermentioning

confidence: 99%

Low bone turnover phenotype in Rett syndrome: results of biochemical bone marker analysis

et al. 2013

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Background:Patients with Rett syndrome (RTT) are at risk of having low bone mass and low-energy fractures. Methods: We characterized bone metabolism by both bone formation and resorption markers in blood in a RTT population of 61 girls and women and 122 well-matched healthy controls. Levels of N-terminal propeptides of collagen type 1 (P1NP), C-terminal telopeptide cross links (CTX), osteocalcin (OC), and bone-specific alkaline phosphatase (B-ALP) were compared between RTT patients and controls in regression models adjusted for BMI, vitamin D status, volumetric bone mineral apparent density of the lumbar spine (vBMAD spine ), and femoral neck (vBMAD neck ). We examined biochemical bone marker levels overall and stratified to persons younger than age 25 y or equal to or older than age 25 y. results: The RTT patients had reduced levels of all biochemical bone markers (P < 0.05), which remained significant in persons younger than 25 y (P ≤ 0.001) regarding P1NP, CTX, and OC. Bone marker levels were not significantly associated to methyl-CpG-binding protein 2 (MECP2) mutation group, walking ability, or previous low-energy fractures. conclusion: Our findings of a low bone turnover state in girls with RTT suggest critical attention to medical treatment of low bone mass in young RTT patients.

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“…Apraxia or motor planning difficulty interferes with nutritional intake (chewing and swallowing) as well as mobility. The exact effect of the MeCP2 protein on bone formation is not yet understood, but central control of bone remodeling is involved at the level of the osteoblast [45][46][47]. On a cellular level, Budden et al [48] explored the etiology behind the low bone mass observed using bone histomorphologic studies in 5 girls with Rett syndrome requiring orthopaedic surgery.…”

Section: Discussionmentioning

confidence: 99%

The effect of low magnitude mechanical stimulation (LMMS) on bone density in patients with Rett syndrome: A pilot and feasibility study

Afzal¹,

Wender

Jones³

et al. 2014

Journal of Pediatric Rehabilitation Medicine

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PURPOSE: Low magnitude mechanical stimulation (LMMS) has been used successfully to promote bone formation in certain patient populations. This study evaluated the feasibility and effectiveness of LMMS on improving bone mineral density (BMD) in patients with Rett syndrome. METHODS: A 12-month crossover pilot study design of 6 months of intervention with LMMS and 6 months without was studied in 14 subjects divided in two subgroups. BMD was assessed using Dual Energy X-ray Absorptiometry (DXA). The levels of 25-hydroxy vitamin D (25OHD), Parathyroid Hormone (PTH), Insulin-Like Growth Factor 1 (IGF-1), and circulating markers of bone resorption (NTx) were analyzed in blood samples. Health questionnaires and diet logs were obtained at 0, 6, and 12 months. RESULTS: Of the 11 subjects who completed the protocol, 9 had an adherence of > 65% and showed an increase in spine BMD Z-scores from the intervention (Z: −2.51) compared to non-intervention period (Z: −2.27) of 0.23 SD (p = 0.048). Following intervention, favorable trends were also observed for IGF-1 (p = 0.06) and right distal femur BMD Z-scores (p = 0.07). CONCLUSIONS: These preliminary results are promising for a larger, placebo-controlled randomized study of subjects with Rett syndrome.

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Bone Mass in Rett Syndrome: Association with Clinical Parameters and MECP2 Mutations

Cited by 23 publications

References 29 publications

Clinical and biological progress over 50 years in Rett syndrome

Clinical and biological progress over 50 years in Rett syndrome

Low bone turnover phenotype in Rett syndrome: results of biochemical bone marker analysis

The effect of low magnitude mechanical stimulation (LMMS) on bone density in patients with Rett syndrome: A pilot and feasibility study

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