Hearing loss in Norwegian adults with achondroplasia

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

Obstructive sleep apnea in Norwegian adults with achondroplasia: a population-based study

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

High prevalence of symptomatic spinal stenosis in Norwegian adults with achondroplasia: a population-based study

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

Fat infiltration in the thigh muscles is associated with symptomatic spinal stenosis and reduced physical functioning in adults with achondroplasia

BackgroundSymptomatic 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.MethodsMFI 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.ResultsSymptomatic 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 &amp;lt; 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 &amp;lt; 0.01), and moderately correlated with the 30sSTS (r = - 0.56, - 0.57, and - 0.59; all p-values &amp;lt; 0.01). There were no significant differences in muscle volumes or physical activity level between the stenosis group and the non-stenosis group.ConclusionIncreased 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.Funding Agencies|Dam Foundation [2019/FO249324]; The Norwegian National Advisory Unit on Rare Disorders (NKSD) [226038, 226053]</p

The first European consensus on principles of management for achondroplasia

none13Achondroplasia 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.noneCormier-Daire V.; AlSayed M.; Ben-Omran T.; de Sousa S.B.; Boero S.; Fredwall S.O.; Guillen-Navarro E.; Irving M.; Lampe C.; Maghnie M.; Mortier G.; Peijin Z.; Mohnike K.Cormier-Daire, V.; Alsayed, M.; Ben-Omran, T.; de Sousa, S. B.; Boero, S.; Fredwall, S. O.; Guillen-Navarro, E.; Irving, M.; Lampe, C.; Maghnie, M.; Mortier, G.; Peijin, Z.; Mohnike, K