Abstract:Background
Previous studies have found a high prevalence of obstructive sleep apnea (OSA) in children with achondroplasia, but clinical studies on this complication in adults with achondroplasia are lacking.
Objectives
This population-based, cross-sectional study investigated the prevalence, severity, and predictive factors of OSA in Norwegian adults with achondroplasia.
Methods
We collected clinical d… Show more
“…2 ). These are among the most clinically important complications of achondroplasia because of their impact on comorbidity, HRQoL, and/or mortality, as confirmed by literature [ 1 , 4 , 18 , 19 , 24 , 26 , 28 , 31 ] and responses of the panel to questions in the modified Delphi study (see “ Discussion ” above and Additional file 1 : Tables S1–S3). Because of the clinical importance of symptomatic spinal stenosis, kyphosis, foramen magnum stenosis and obstructive sleep apnea, evaluation of the impact of vosoritide on these complications in future clinical trials should be considered.…”
Section: Discussionmentioning
confidence: 61%
“…On the other hand, symptomatic spinal stenosis and kyphosis, and related back pain, are most prevalent in adults with achondroplasia and may still be altered if treatment is started at a later age, when spinal growth can still be improved. Similarly, obstructive sleep apnea can develop in infancy, but may also occur or relapse in adults with achondroplasia [ 18 ] and so might benefit from later treatment. Fig.…”
Section: Discussionmentioning
confidence: 99%
“…Furthermore, the respiratory sleep disturbance associated with achondroplasia, particularly in young children, is considered more complex due to the frequent combination of central and obstructive components. Although there are currently no published comparative data to confirm increased mortality in individuals with achondroplasia due to obstructive sleep apnea, studies have shown a very high prevalence of obstructive sleep apnea in children (often 50% or higher) and adults (59%) with the disorder, compared to 1–6% in the general population [ 18 , 28 ].…”
Background
Achondroplasia is associated with disproportionate short stature and significant and potentially severe medical complications. Vosoritide is the first medicine to treat the underlying cause of achondroplasia and data from phase 3 and phase 2 extension studies showed effects on growth and body proportions. However, there are currently no long-term data available on the direct impact on endpoints such as medical complications and health-related quality of life (HRQoL). This study explored the perceived impact of achondroplasia on medical complications, HRQoL, healthcare resource use and mortality, and potential modifying effects of vosoritide, based on published evidence and expert opinion. Structured expert opinion was obtained by an international modified Delphi study among 14 experts in managing achondroplasia performed on a virtual platform and consisting of an explorative phase followed by an anonymous individual rating round.
Results
Overall, the panelists expect that in individuals starting long-term treatment between 2 years of age and puberty, growth velocity increases observed in the clinical trials will be maintained until final height is reached (92% agreement) and will likely result in clinically meaningful improvements in upper-to-lower body segment ratio (85%). Earlier treatment initiation will likely result in a greater final height (100%) and more likely improve proportionality (92%) than later treatment. Although current data are limited, ≥ 75% of panelists find it conceivable that the earlier long-term treatment is started, the greater the probability of a positive effect on the lifetime incidence of symptomatic spinal stenosis, kyphosis, obstructive sleep apnea, and foramen magnum stenosis. These are among the most clinically important complications of achondroplasia because of their high impact on comorbidity, mortality, and/or HRQoL. A positive effect of vosoritide on the incidence of surgeries through lifetime was considered more likely with earlier long-term treatment (90%).
Conclusions
This explorative study, based on international expert opinion, provides further insight into the medical and functional impacts of achondroplasia and how these might be modified through long-term use of vosoritide. The results can be used to guide the direction and design of future research to validate the assumptions and to discuss potential treatment outcomes with disease modifying therapies with families and clinicians.
“…2 ). These are among the most clinically important complications of achondroplasia because of their impact on comorbidity, HRQoL, and/or mortality, as confirmed by literature [ 1 , 4 , 18 , 19 , 24 , 26 , 28 , 31 ] and responses of the panel to questions in the modified Delphi study (see “ Discussion ” above and Additional file 1 : Tables S1–S3). Because of the clinical importance of symptomatic spinal stenosis, kyphosis, foramen magnum stenosis and obstructive sleep apnea, evaluation of the impact of vosoritide on these complications in future clinical trials should be considered.…”
Section: Discussionmentioning
confidence: 61%
“…On the other hand, symptomatic spinal stenosis and kyphosis, and related back pain, are most prevalent in adults with achondroplasia and may still be altered if treatment is started at a later age, when spinal growth can still be improved. Similarly, obstructive sleep apnea can develop in infancy, but may also occur or relapse in adults with achondroplasia [ 18 ] and so might benefit from later treatment. Fig.…”
Section: Discussionmentioning
confidence: 99%
“…Furthermore, the respiratory sleep disturbance associated with achondroplasia, particularly in young children, is considered more complex due to the frequent combination of central and obstructive components. Although there are currently no published comparative data to confirm increased mortality in individuals with achondroplasia due to obstructive sleep apnea, studies have shown a very high prevalence of obstructive sleep apnea in children (often 50% or higher) and adults (59%) with the disorder, compared to 1–6% in the general population [ 18 , 28 ].…”
Background
Achondroplasia is associated with disproportionate short stature and significant and potentially severe medical complications. Vosoritide is the first medicine to treat the underlying cause of achondroplasia and data from phase 3 and phase 2 extension studies showed effects on growth and body proportions. However, there are currently no long-term data available on the direct impact on endpoints such as medical complications and health-related quality of life (HRQoL). This study explored the perceived impact of achondroplasia on medical complications, HRQoL, healthcare resource use and mortality, and potential modifying effects of vosoritide, based on published evidence and expert opinion. Structured expert opinion was obtained by an international modified Delphi study among 14 experts in managing achondroplasia performed on a virtual platform and consisting of an explorative phase followed by an anonymous individual rating round.
Results
Overall, the panelists expect that in individuals starting long-term treatment between 2 years of age and puberty, growth velocity increases observed in the clinical trials will be maintained until final height is reached (92% agreement) and will likely result in clinically meaningful improvements in upper-to-lower body segment ratio (85%). Earlier treatment initiation will likely result in a greater final height (100%) and more likely improve proportionality (92%) than later treatment. Although current data are limited, ≥ 75% of panelists find it conceivable that the earlier long-term treatment is started, the greater the probability of a positive effect on the lifetime incidence of symptomatic spinal stenosis, kyphosis, obstructive sleep apnea, and foramen magnum stenosis. These are among the most clinically important complications of achondroplasia because of their high impact on comorbidity, mortality, and/or HRQoL. A positive effect of vosoritide on the incidence of surgeries through lifetime was considered more likely with earlier long-term treatment (90%).
Conclusions
This explorative study, based on international expert opinion, provides further insight into the medical and functional impacts of achondroplasia and how these might be modified through long-term use of vosoritide. The results can be used to guide the direction and design of future research to validate the assumptions and to discuss potential treatment outcomes with disease modifying therapies with families and clinicians.
“…An increasing number of studies have emerged in recent years describing potential medical complications and impact on psychosocial health in adults. Among the most severe medical complications in adulthood are symptomatic spinal stenosis, obstructive sleep apnoea, hearing loss, hypertension, and obesity [13][14][15][16][17][18][19]. Reduced physical functioning, impaired ability to perform activities of daily living, reduced work participation, chronic pain, depression, anxiety, and low self-esteem are other challenges commonly reported in the adult achondroplasia population [14,[20][21][22][23].…”
Background
Achondroplasia is a genetic condition that can cause complications across the lifespan. While complications in childhood are well documented, the natural history of achondroplasia in adults has, until recently, been relatively lacking, and little is known about the care they receive or how they access it. The European Achondroplasia Forum undertook two exploratory surveys, one for healthcare professionals (HCPs) and one for patient advocacy group (PAG) representatives, to gain an understanding of current practices of the transition process of individuals with achondroplasia from paediatric to adult services and how adults perceive their care.
Results
Most HCP respondents followed up more children than adults, and 8/15 responded that individuals did not transition to an adult multidisciplinary team (MDT) after paediatric care. Of 10 PAG respondents, none considered the experience of transition to adult services as good or very good and 50% considered it to be poor or very poor. A total of 64% (7/11) described the coordination of transition to adult services as “Not satisfactory” or “Poor”. HCPs and PAG representatives largely agreed on the core specialists involved in adult care (orthopaedic surgeons, physiotherapists, rehabilitation specialists, rheumatologists, clinical geneticists). However, there was a discrepancy in the understanding of healthcare needs outside of this, with PAG representatives selecting neurosurgeons and genetic counsellors, while HCPs selected pulmonologists and obstetricians/gynaecologists. There was agreement between HCP and PAG respondents on the key barriers to effective care of adults with achondroplasia, with lack of an adult MDT, lack of interest from individuals in accessing care, and less experience in adult than paediatric MDTs ranking highly.
Conclusions
This study indicates that the care and follow up of adults with achondroplasia is challenging. Individuals are often lost to, or decline, follow up as they leave paediatric care, and it is largely unknown how, where, and why adults with achondroplasia access care later in life. Lifelong, multidisciplinary specialist care led by an identified physician should be accessible to all individuals with achondroplasia. It is important to ensure barriers to optimal care are addressed to enable access to appropriate care for all individuals with achondroplasia.
“…People with achondroplasia have a normal, or near normal life expectancy [ 5 ] and require lifelong management by an experienced multidisciplinary team (MDT) [ 8 ]. Co-morbidities throughout the lifetime of an individual with achondroplasia may include spinal stenosis, thoracolumbar kyphosis, sleep apnoea, obesity, and pain [ 9 – 14 ], all of which can impact significantly on quality of life and mental health [ 15 – 18 ]. Serious complications may occur in early infancy, including craniocervical junction compression, otitis media, craniofacial issues, hydrocephalus, restrictive breathing problems and central apnoea [ 5 , 9 , 10 , 19 ], underlining the need for specialist management.…”
Background
Achondroplasia is the most common form of skeletal dysplasia, with serious comorbidities and complications that may occur from early infancy to adulthood, requiring lifelong management from a multidisciplinary team expert in the condition The European Achondroplasia Forum guiding principles of management highlight the importance of accurate diagnosis and timely referral to a centre specialised in the management of achondroplasia to fully support individuals with achondroplasia and their families, and to appropriately plan management. The European Achondroplasia Forum undertook an exploratory audit of its Steering Committee to ascertain the current situation in Europe and to understand the potential barriers to timely diagnosis and referral.
Results
Diagnosis of achondroplasia was primarily confirmed prenatally (66.6%), at Day 0 (12.8%) or within one month after birth (12.8%). For suspected and confirmed cases of achondroplasia, a greater proportion were identified earlier in the prenatal period (87.1%) with fewer diagnoses at Day 0 (5.1%) or within the first month of life (2.6%). Referral to a specialist centre took place after birth (86.6%), predominantly within the first month, although there was a wide variety in the timepoint of referral between countries and in the time lapsed between suspicion or confirmed diagnosis of achondroplasia and referral to a specialist centre.
Conclusions
The European Achondroplasia Forum guiding principles of management recommend diagnosis of achondroplasia as early as possible. If concerns are raised at routine ultrasound, second line investigation should be implemented so that the diagnosis can be reached as soon as possible for ongoing management. Clinical and radiological examination supported by molecular testing is the most effective way to confirm diagnosis of achondroplasia after birth. Referral to a centre specialised in achondroplasia care should be made as soon as possible on suspicion or confirmation of diagnosis. In countries or regions where there are no official skeletal dysplasia reference or specialist centres, priority should be given to their creation or recognition, together with incentives to improve the structure of the existing multidisciplinary team managing achondroplasia. The length of delay between diagnosis of achondroplasia and referral to a specialist centre warrants further research.
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