Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 13 de 13
Filter
1.
Lancet Child Adolesc Health ; 8(4): 301-310, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38485412

ABSTRACT

Achondroplasia is the most common form of dwarfism in humans, caused by a common pathogenic variant in the gene encoding fibroblast growth factor receptor 3, FGFR3, which impairs the process of endochondral ossification of the growing skeleton. In this Review, we outline the clinical and genetic hallmarks of achondroplasia and related FGFR3 conditions, the natural history and impact of achondroplasia over a patient's lifespan, and diagnosis and management options. We then focus on the new and emerging drug therapies that target the underlying pathogenesis of this condition. These new options are changing the natural growth patterns of achondroplasia, with the prospect of better long-term health outcomes for patients.


Subject(s)
Achondroplasia , Child , Humans , Achondroplasia/genetics , Achondroplasia/therapy
2.
Genet Med ; 25(10): 100920, 2023 10.
Article in English | MEDLINE | ID: mdl-37330695

ABSTRACT

PURPOSE: Skeletal dysplasia are heterogeneous conditions affecting the skeleton. Common nutrition issues include feeding difficulties, obesity, and metabolic complications. This systematic scoping review aimed to identify key nutrition issues, management strategies, and gaps in knowledge regarding nutrition in skeletal dysplasia. METHODS: The databases Ovid MEDLINE, Ovid EMBASE, Ebsco CINAHL, Scopus, and Cochrane Central Register of Controlled Trials and Database of Systematic Reviews were searched. Reference lists and citing literature for included studies were searched. Eligible studies included participants with skeletal dysplasia and described: anthropometry, body composition, nutrition-related biochemistry, clinical issues, dietary intake, measured energy or nutrition requirements, or nutrition interventions. RESULTS: The literature search identified 8509 references from which 138 studies were included (130 observational, 3 intervention, 2 systematic reviews, and 3 clinical guidelines). Across 17 diagnoses identified, most studies described osteogenesis imperfecta (n = 50) and achondroplasia or hypochondroplasia (n = 47). Nutrition-related clinical issues, biochemistry, obesity, and metabolic complications were most commonly reported, and few studies measured energy requirements (n = 5). CONCLUSION: Nutrition-related comorbidities are documented in skeletal dysplasia; yet, evidence to guide management is scarce. Evidence describing nutrition in rarer skeletal dysplasia conditions is lacking. Advances in skeletal dysplasia nutrition knowledge is needed to optimize broader health outcomes.


Subject(s)
Dwarfism , Osteochondrodysplasias , Humans , Comorbidity , Obesity , Systematic Reviews as Topic
3.
Orphanet J Rare Dis ; 18(1): 35, 2023 02 22.
Article in English | MEDLINE | ID: mdl-36814258

ABSTRACT

BACKGROUND: Symptomatic spinal stenosis is a prevalent complication in adults with achondroplasia. Increased muscle fat infiltration (MFI) and reduced thigh muscle volumes have also been reported, but the pathophysiology is poorly understood. We explored whether the increased MFI and reduced thigh muscle volumes were associated with the presence of symptomatic spinal stenosis and physical functioning. METHODS: MFI and thigh muscle volumes were assessed by MRI in 40 adults with achondroplasia, and compared to 80 average-statured controls, matched for BMI, gender, and age. In achondroplasia participants, the six-minute walk-test (6MWT), the 30-s sit-to-stand test (30sSTS), and a questionnaire (the IPAQ) assessed physical functioning. RESULTS: Symptomatic spinal stenosis was present in 25 of the participants (the stenosis group), while 15 did not have stenosis (the non-stenosis group). In the stenosis group, 84% (21/25) had undergone at least one spinal decompression surgery. The stenosis group had significantly higher MFI than the non-stenosis group, with an age-, gender and BMI-adjusted difference in total MFI of 3.3 percentage points (pp) (95% confidence interval [CI] 0.04 to 6.3 pp; p = 0.03). Compared to matched controls, the mean age-adjusted difference was 3.3 pp (95% CI 1.7 to 4.9 pp; p < 0.01). The non-stenosis group had MFI similar to controls (age-adjusted difference - 0.9 pp, 95% CI - 3.4 to 1.8 pp; p = 0.51). MFI was strongly correlated with the 6MWT (r = - 0.81, - 0.83, and - 0.86; all p-values < 0.01), and moderately correlated with the 30sSTS (r = - 0.56, - 0.57, and - 0.59; all p-values < 0.01). There were no significant differences in muscle volumes or physical activity level between the stenosis group and the non-stenosis group. CONCLUSION: Increased MFI in the thigh muscles was associated with the presence of symptomatic spinal stenosis, reduced functional walking capacity, and reduced lower limb muscle strength. The causality between spinal stenosis, accumulation of thigh MFI, and surgical outcomes need further study. We have demonstrated that MRI might serve as an objective muscle biomarker in future achondroplasia studies, in addition to functional outcome measures. The method could potentially aid in optimizing the timing of spinal decompression surgery and in planning of post-surgery rehabilitation.


Subject(s)
Achondroplasia , Spinal Stenosis , Humans , Adult , Spinal Stenosis/complications , Spinal Stenosis/surgery , Thigh , Muscle, Skeletal , Magnetic Resonance Imaging/methods , Achondroplasia/complications
4.
Orphanet J Rare Dis ; 17(1): 224, 2022 06 13.
Article in English | MEDLINE | ID: mdl-35698202

ABSTRACT

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.


Subject(s)
Achondroplasia , Quality of Life , Achondroplasia/complications , Achondroplasia/drug therapy , Delphi Technique , Expert Testimony , Humans , Motivation , Natriuretic Peptide, C-Type/analogs & derivatives
5.
Orphanet J Rare Dis ; 16(1): 468, 2021 11 04.
Article in English | MEDLINE | ID: mdl-34736503

ABSTRACT

BACKGROUND: Achondroplasia is the most common form of disproportionate skeletal dysplasia. The condition is caused by a mutation in the FGFR3 gene, affecting endochondral bone growth, including the craniofacial anatomy. Recurrent otitis media infections, chronic middle ear effusion, and hearing loss are common in children with achondroplasia, but few studies have investigated hearing loss in adults with this condition. OBJECTIVES: This population-based study investigated the prevalence, severity, and type of hearing loss in Norwegian adults with achondroplasia. METHODS: We collected data on 45 adults with genetically confirmed achondroplasia: 23 men and 22 women, aged 16-70 years. All participants underwent a comprehensive audiologic assessment, including medical history, pure-tone audiometry, speech audiometry, and impedance audiometry. According to the Global Burden of Disease classification, pure-tone average ≥ 20 decibel hearing level (dB HL) was considered clinically significant hearing loss. RESULTS: Insertion of ventilation tubes had been performed in 44% (20/45) of the participants, 49% (22/45) had a history of adenoidectomy, while 20% (9/45) used hearing aids. Hearing loss in at least one ear was found in 53% (24/45) of the participants; in 57% (13/23) of the men and 50% (11/22) of the women. In the youngest age group (age 16-44 years), 50% (14/28) had hearing loss, although predominantly mild (20-34 dB HL). An abnormal tympanometry (Type B or C) was found in 71% (32/45) of the participants. The majority (15/24) had conductive hearing loss, or a combination of conductive and sensorineural hearing loss (8/24). CONCLUSIONS: Adults with achondroplasia are at increased risk of early hearing loss. Our findings underline the importance of a regular hearing assessment being part of standard care in achondroplasia, including adolescents and young adults. In adult patients diagnosed with hearing loss, an evaluation by an otolaryngologist should be considered, and the need for hearing aids, assistive listening devices, and workplace and educational accommodations should be discussed. Clinical trial registration ClinicalTrials.gov identifier NCT03780153.


Subject(s)
Achondroplasia , Deafness , Hearing Loss, Sensorineural , Hearing Loss , Achondroplasia/complications , Achondroplasia/genetics , Acoustic Impedance Tests , Adolescent , Adult , Aged , Audiometry, Pure-Tone , Cross-Sectional Studies , Female , Hearing Loss/etiology , Humans , Male , Middle Aged , Norway , Young Adult
6.
Orphanet J Rare Dis ; 16(1): 333, 2021 07 31.
Article in English | MEDLINE | ID: mdl-34332609

ABSTRACT

Achondroplasia is the most common type of skeletal dysplasia, caused by a recurrent pathogenic variant in the fibroblast growth factor receptor 3 (FGFR3). The management of achondroplasia is multifaceted, requiring the involvement of multiple specialties across the life course. There are significant unmet needs associated with achondroplasia and substantial differences in different countries with regard to delivery of care. To address these challenges the European Achondroplasia Forum (EAF), a network of senior clinicians and orthopaedic surgeons from Europe and the Middle East representative of the achondroplasia clinical community, came together with the overall aim of improving patient outcomes. The EAF developed a consensus on guiding principles of management of achondroplasia to provide a basis for developing optimal care in Europe. All members of the EAF were invited to submit suggestions for guiding principles of management, which were consolidated and then discussed during a meeting in December 2020. The group voted anonymously on the inclusion of each principle, with the requirement of a 75% majority at the first vote to pass the principle. A vote on the level of agreement was then held. A total of six guiding principles were developed, which cover management over the lifetime of a person with achondroplasia. The principles centre on the lifelong management of achondroplasia by an experienced multidisciplinary team to anticipate and manage complications, support independence, and improve quality of life. There is focus on timely referral to a physician experienced in the management of achondroplasia on suspicion of the condition, shared decision making, the goals of management, access to adaptive measures to enable those with achondroplasia to access their environment, and the importance of ongoing monitoring throughout adolescence and adulthood. All principles achieved the 75% majority required for acceptance at the first vote (range 91-100%) and a high level of agreement (range 8.5-9.6). The guiding principles of management for achondroplasia provide all healthcare professionals, patient advocacy groups and policy makers involved in the management of achondroplasia with overarching considerations when developing health systems to support the management of achondroplasia.


Subject(s)
Achondroplasia , Quality of Life , Achondroplasia/therapy , Adolescent , Adult , Consensus , Europe , Humans , Longitudinal Studies , Receptor, Fibroblast Growth Factor, Type 3/genetics
8.
Orphanet J Rare Dis ; 16(1): 156, 2021 04 07.
Article in English | MEDLINE | ID: mdl-33827611

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 data on 49 participants. Participants without a preexisting diagnosis of OSA had an overnight sleep registration. OSA was defined as an apnea-hypopnea index (AHI) ≥ 5 plus characteristic clinical symptoms, or AHI ≥ 15. We used the Berlin Questionnaire to assess clinical symptoms of OSA. RESULTS: OSA was found in 59% (29/49) of the participants (95% confidence interval 44 to 73%), of whom 59% (17/29) had moderate to severe OSA (AHI ≥ 15), and 48% (14/29) were previously undiagnosed. Variables predictive of OSA were: excessive daytime sleepiness; unrested sleep; loud snoring; observed nocturnal breathing stops; hypertension; age > 40 years; and BMI > 30 kg/m2. CONCLUSION: OSA was highly prevalent in Norwegian adults with achondroplasia, which we believe is representative of this population worldwide. Follow-up of adults with achondroplasia should include assessment of symptoms and signs of OSA, with a low threshold for conducting an overnight sleep registration if findings suggestive of OSA are present.


Subject(s)
Achondroplasia , Disorders of Excessive Somnolence , Sleep Apnea, Obstructive , Achondroplasia/epidemiology , Adult , Child , Cross-Sectional Studies , Humans , Sleep Apnea, Obstructive/epidemiology , Snoring
9.
Genet Med ; 23(4): 732-739, 2021 04.
Article in English | MEDLINE | ID: mdl-33204020

ABSTRACT

PURPOSE: An increased cardiovascular mortality has been reported in achondroplasia. This population-based, case-control study investigated cardiovascular risk factors and body composition in Norwegian adults with achondroplasia. METHODS: We conducted anthropometric, clinical, and laboratory assessments in 49 participants with achondroplasia, of whom 40 completed magnetic resonance imaging (MRI) for body composition analysis. Controls consisted of 98 UK Biobank participants, matched for body mass index (BMI), sex, and age. RESULTS: Participants were well matched for BMI (33.3 versus 32.5 kg/m2) and sex, but achondroplasia participants were younger than controls (mean age 41.1 versus 54.3 years). Individuals with achondroplasia had lower age-adjusted mean blood pressure, total and low-density lipoprotein (LDL) cholesterol, and triglycerides compared with controls, but similar fasting glucose and HbA1c values. Age-adjusted mean visceral fat store was 1.9 versus 5.3 L (difference -2.7, 95% confidence interval [CI] -3.6 to -1.9; P < 0.001), abdominal subcutaneous fat was 6.0 versus 11.2 L (-4.7, 95% CI -5.9 to -3.4; P < 0.001), and liver fat was 2.2 versus 6.9% (-2.8, 95% CI -5.2 to -0.4; P = 0.02). CONCLUSION: Despite a high BMI, the cardiovascular risks appeared similar or lower in achondroplasia compared with controls, indicating that other factors might contribute to the increased mortality observed in this condition.


Subject(s)
Achondroplasia , Cardiovascular Diseases , Achondroplasia/epidemiology , Achondroplasia/genetics , Adult , Body Composition , Body Mass Index , Cardiovascular Diseases/epidemiology , Case-Control Studies , Heart Disease Risk Factors , Humans , Risk Factors
11.
Orphanet J Rare Dis ; 15(1): 123, 2020 05 25.
Article in English | MEDLINE | ID: mdl-32450891

ABSTRACT

BACKGROUND: Symptomatic spinal stenosis (SSS) is a well-known medical complication in achondroplasia. The reported prevalence of SSS is 10 to 30%, an estimate based on small studies or selected populations. No population-based studies exist currently. Furthermore, the relationship between SSS and physical functioning has not been investigated in detail. The aims of this study were to describe the prevalence of SSS in Norwegian adults with achondroplasia, and to explore the impact of SSS on physical functioning. METHODS: This was a population-based study on Norwegian community-dwelling adults with genetically confirmed achondroplasia. Prevalence of SSS was defined by clinical symptoms, and confirmed by imaging or surgical reports. Physical functioning was assessed by walking capacity (6-min walk test), hand strength (Grippit), and activities of daily living (the Health Assessment Questionnaire, HAQ). Pain was assessed by pain site locations and intensity (Numeric Rating Scale, NRS). RESULTS: In total, 50 participants were included (27 males, 23 females). Median age was 41 years (range 16 to 87 years), 34 (68%) had SSS. The estimated median age at first symptom onset was 33 years (95% confidence interval (CI) 29 to 43 years), range 10 to 67 years. The majority had multiple spinal levels affected. The walking distance was 110 m shorter in the SSS group (95% CI - 172 to - 40 m) as compared with the non-SSS group (p < 0.01). There was no considerable difference in hand strength between the two groups. Mean HAQ scores (0-3) for walking and hygiene were significantly higher in the SSS group, reflecting more activity limitations. Mean differences were 0.9 (95% CI 0.3 to 1.4, p < 0.01) and 0.6 (95% CI 0.2 to 1.0, p < 0.01). Pain intensity (NRS 0-10) was also significantly higher in the SSS group with a mean difference of 3.2 (95% CI 0.6 to 5.6, p = 0.02). CONCLUSIONS: SSS was highly prevalent in Norwegian adults with achondroplasia, with symptom onset at young age, and multiple spinal levels affected. The presence of SSS was associated with reduced walking distance, activity limitations, and more pain. The findings underline the importance of thorough assessment and monitoring of SSS in achondroplasia, including a formal assessment of physical functioning.


Subject(s)
Achondroplasia , Spinal Stenosis , Achondroplasia/epidemiology , Activities of Daily Living , Adolescent , Adult , Aged , Aged, 80 and over , Child , Female , Humans , Lumbar Vertebrae , Male , Middle Aged , Prevalence , Spinal Stenosis/epidemiology , Young Adult
12.
Clin Genet ; 97(1): 179-197, 2020 01.
Article in English | MEDLINE | ID: mdl-30916780

ABSTRACT

This article provides an overview of the current knowledge on medical complications, health characteristics, and psychosocial issues in adults with achondroplasia. We have used a scoping review methodology particularly recommended for mapping and summarizing existing research evidence, and to identify knowledge gaps. The review process was conducted in accordance with the PRISMA-ScR guidelines (Preferred Reporting Items for Systematic reviews and Meta-Analyses Extension for Scoping Reviews). The selection of studies was based on criteria predefined in a review protocol. Twenty-nine publications were included; 2 reviews, and 27 primary studies. Key information such as reference details, study characteristics, topics of interest, main findings and the study author's conclusion are presented in text and tables. Over the past decades, there has only been a slight increase in publications on adults with achondroplasia. The reported morbidity rates and prevalence of medical complications are often based on a few studies where the methodology and representativeness can be questioned. Studies on sleep-related disorders and pregnancy-related complications were lacking. Multicenter natural history studies have recently been initiated. Future studies should report in accordance to methodological reference standards, to strengthen the reliability and generalizability of the findings, and to increase the relevance for implementing in clinical practice.


Subject(s)
Achondroplasia/complications , Achondroplasia/mortality , Achondroplasia/physiopathology , Achondroplasia/psychology , Adult , Bone Diseases/complications , Female , Female Urogenital Diseases/complications , Humans , Obesity/complications , Otorhinolaryngologic Diseases/complications , Pain/complications , Pregnancy , Quality of Life , Reproducibility of Results , Respiration Disorders/complications , Sleep Wake Disorders , Spinal Stenosis/complications
13.
Am J Med Genet A ; 179(9): 1745-1755, 2019 09.
Article in English | MEDLINE | ID: mdl-31240834

ABSTRACT

Individuals with achondroplasia have a high prevalence of obesity and increased risk of cardiovascular disease. Fat distribution, diet, and caloric intake are known risk factors, but the literature concerning diet and energy balance in achondroplasia is limited. The main aim of this study was to describe the anthropometrics, diet, and resting energy expenditure (REE) in a Norwegian adult achondroplasia population. Here, we present a descriptive cross-sectional study with the following variables: anthropometrics, the SmartDiet questionnaire, and dietary records. In addition, REE was measured and estimated using indirect calorimetry and prediction equations. A total of 33 adults with achondroplasia participated with a mean age of 40 years. Mean body mass index was 34.1 kg/m2 , and mean waist circumference was 94.1 cm for men and 82.2 cm for women. Their diets were classified as unhealthy (38%) or in need of improvement (62%). The mean REE values for the total group were 21 kcal/kg for the male (n = 15) and 20 kcal/kg for the female (n = 18). This study revealed a high frequency of central obesity and unhealthy dietary habits in Norwegian adults with achondroplasia. Mean energy intake was low and only 10% higher than the mean REE, and does not explain the high prevalence of abdominal obesity in our population.


Subject(s)
Achondroplasia/diet therapy , Cardiovascular Diseases/diet therapy , Diet , Obesity/diet therapy , Achondroplasia/complications , Achondroplasia/metabolism , Achondroplasia/physiopathology , Adult , Anthropometry/methods , Body Composition/physiology , Cardiovascular Diseases/complications , Cardiovascular Diseases/metabolism , Cardiovascular Diseases/physiopathology , Energy Metabolism , Exercise/physiology , Female , Humans , Male , Middle Aged , Obesity/complications , Obesity/metabolism , Obesity/physiopathology , Rest/physiology , Surveys and Questionnaires
SELECTION OF CITATIONS
SEARCH DETAIL
...