Search Results (33)

Background/Objectives: Achondroplasia, the most common form of skeletal dysplasia, poses significant challenges for procedural sedation due to distinct anatomical and physiological features. This study evaluated the safety, effectiveness, and imaging quality of a standardized sedation protocol for magnetic resonance imaging (MRI) in children with achondroplasia. Methods: We conducted a single-center, retrospective analysis of 22 MRI procedures in 12 pediatric patients. Intravenous midazolam and propofol were used as primary sedatives, with continuous monitoring and standardized dosing. Sedation parameters were compared between children aged <1 year and children aged ≥1 year. Results: The median sedation duration was 35 (25–65) min, and the median recovery time was 9 (5–14) min. No significant differences were found between age groups in midazolam dose (<1 year: 0.15 ± 0.05 mg/kg vs. ≥1 year: 0.13 ± 0.04 mg/kg; p = 0.238), propofol induction (2.26 ± 1.14 vs. 1.80 ± 0.52 mg/kg; p = 0.375), or infusion rate (3.18 ± 2.74 vs. 5.13 ± 2.65 mg/kg/h; p = 0.203), indicating protocol consistency. High-quality images were obtained in all cases. In one case (4.5%), self-limited desaturation to 92% occurred, with no intervention required. No airway instrumentation or other complications were reported. Conclusions: This protocol provides safe, effective, and reproducible sedation in children with achondroplasia, ensuring high-quality MRI with minimal adverse events. Full article

Accessible housing plays a vital role in promoting independent living and quality of life for people with disabilities. However, the existing design standards often fail to address the specific needs of diverse disability groups. This study aims to establish architectural and habitability criteria for housing adapted to various disabilities, including wheelchair users, individuals with achondroplasia (little people), Autism Spectrum Disorder (ASD) and Down syndrome, individuals with visual and hearing impairments, and older adults, by integrating international frameworks and prior research. The Analytic Hierarchy Process (AHP) was used to prioritize key factors in the housing design. The factors analyzed included autonomy, independence, safety, comfort, communication, and mobility. Findings reveal that autonomy consistently emerged as the most relevant criterion across groups, particularly for older adults (61.8%), wheelchair users (83%) and little people (64%). Secondary priorities varied: mobility was emphasized by wheelchair users (77%), communication by visually impaired individuals (64%), and comfort by deaf and hard of hearing participants (43%). The results underscore the need for housing solutions that reflect the priorities of each disability group. This study contributes by validating user-centered design criteria and offering a framework to guide inclusive housing policies and practices. By highlighting needs, it bridges the gap between generic accessibility standards and design. These findings support policy development and enrich the literature by incorporating unique resident-centered perspectives and overlooked indicators of housing accessibility and inclusive residential design. Full article

Background: The use of patient-reported outcomes is essential to understand and manage health-related quality of life (HRQOL) in youth with lifelong disabilities. This study evaluated HRQOL in youth with physical disorders and examined its relationship with mobility. Methods: We conducted an IRB-approved retrospective study in which we administered the parent-reported Pediatric Outcomes Data Collection Instrument (PODCI) and Gross Motor Function Measure section D (GMFM-D) to ambulatory youth aged 2–18 years with cerebral palsy (CP; Gross Motor Function Classification System II; n = 258), arthrogryposis (n = 138), achondroplasia (n = 102), and Morquio syndrome (n = 52) during clinical visits to a gait lab. The PODCI has two validated versions, child and adolescent, that assess perceptions about mobility, happiness, and pain. Differences in HRQOL between diagnostic groups, between age groups, and compared with non-disabled youth were examined using non-parametric tests. The relationship between GMFM-D and PODCI scores was analyzed with Pearson’s correlations. Results: Both age cohorts within all diagnosis groups demonstrated higher pain and lower mobility compared with non-disabled youth (p < 0.015). Happiness was lower for both age groups with CP and arthrogryposis, and for the child group with Morquio syndrome compared with non-disabled youth (p < 0.002). In diagnostic groups in both age spans, Global Function was higher (p < 0.0001) for those with achondroplasia compared with other groups. Despite functional differences, there were no significant differences between diagnostic groups in pain scores (p > 0.10). Happiness was lower in the group with CP compared with that with achondroplasia (p = 0.01). GMFM-D was related to PODCI mobility scores for all diagnoses (r = 0.31 to 0.79, p < 0.03) but was not correlated with happiness (r = −0.16 to 0.092; p > 0.14); GMFM-D and PODCI pain scores were associated only for the child group with achondroplasia (r = 0.355; p < 0.001). Conclusions: Significant limitations in HRQOL are present in youth with physical disabilities. Pain levels were higher than those of non-disabled youth, but pain was not related to lower motor function. Happiness was not related to gross motor function, suggesting the need to examine other factors when mental health concerns are present in youth with disabilities. Full article

Background/Objectives: This report details a rare instance of an infant with achondroplasia developing acute tetraparesis after a cervical whiplash injury, highlighting key multidisciplinary management considerations and specific anesthetic strategies to mitigate potential risks. Case presentation: A 1-year-old boy with achondroplasia presented with acute tetraparesis after a whiplash injury. Initial craniocervical computed tomography demonstrated a reduced volume of the posterior fossa, foramen magnum stenosis, and ventriculomegaly, without any fractures or dislocations. Moreover, magnetic resonance imaging (MRI) revealed pathological signal changes in the medulla oblongata, cervical spinal cord in segments C1 and C2, and the posterior atlantoaxial ligament. After initial conservative therapy and head immobilization using a soft cervical collar, partial remission of the tetraparesis was achieved. Two weeks post-injury, microsurgical posterior fossa decompression extending to the foramen magnum and C1 laminectomy was performed under general anesthesia with intraoperative neuromonitoring. Following an unsuccessful intubation attempt using a fiberoptic bronchoscope, successful airway management was achieved using a combined technique incorporating video laryngoscopy. Venous access was secured under ultrasound guidance. The patient exhibited complete remission of neurological symptoms by the third postoperative month during follow-up. Conclusions: This case report underscores the crucial need for a multidisciplinary approach in managing children with achondroplasia, especially with foramen magnum stenosis and complex cervical spine injuries. Anesthetic management required meticulously planned airway strategies using advanced techniques like video laryngoscopy and fiberoptic bronchoscopy to reduce airway risks. It also highlights the importance of conservative therapy paired with timely neurosurgical intervention, resulting in the patient’s full recovery. Full article

Background: Frontal knee malalignments are hallmarks of Achondroplasia (ACH), along with disproportional short stature. Typically, X-rays are used to assess them, but 3D gait analysis (3DGA) may additionally be used to evaluate dynamic knee function. The research questions were as follows: (1) What is the relationship between X-rays and 3DGA in ACH? (2) Do children with ACH have abnormal frontal knee kinematics and kinetics? (3) Are there aspects of 3DGA that relate to knee symptoms? Methods: A total of 62 knees of 31 children with ACH (age: 11.1 ± 4.3 years, 34 symptomatic knees) underwent 3DGA and X-ray as part of their standard clinical care. X-rays were analyzed for mechanical tibiofemoral angle (mTFA). Relationships between X-rays and 3DGA were determined. Sixty-two knees of 31 age-matched typically developing (TD) children served as references for 3DGA. Frontal knee kinematics (including thrust RoM) and adduction moments (KAMs) were compared. Multiple regression was performed for measurements associated with KAM, and ANOVA was used to compare TD and ACH knees with and without pain. Results: There was a high correlation between static frontal knee angles and mTFA (r = 0.93, p < 0.001, mean difference = −2.9°). ACH knees with a regular mTFA also showed significantly increased KAM. Multiple regression analysis showed that mTFA was the most relevant predictor of KAM (R² = 0.41–0.75). Symptomatic knees (n = 34/62) experienced significantly more knee RoM in early stance than asymptomatic knees. Conclusions: Three-dimensional gait analysis may be an objective screening method for dynamic knee alignment and stability and may complement radiography in monitoring ACH. Symptoms may depend on knee thrust, while the impact of altered KAM needs further study. Full article

This retrospective study assessed anatomical characteristics of cervicomedullary compression in children with achondroplasia. Twelve anatomical parameters were analyzed (foramen magnum diameter and area; myelon area; clivus length; tentorium and occipital angles; brainstem volume outside the posterior fossa; and posterior fossa, cerebellum, supratentorial ventricular system, intracranial cerebrospinal fluid, and fourth ventricle volumes) from sagittal and transversal T1- and T2-weighted magnetic resonance imaging (MRI) scans from 37 children with achondroplasia aged ≤ 4 years (median [range] 0.8 [0.1–3.6] years) and compared with scans from 37 children without achondroplasia (median age 1.5 [0–3.9] years). Mann–Whitney U testing was used for between-group comparisons. Foramen magnum diameter and area were significantly smaller in children with achondroplasia compared with the reference group (mean 10.0 vs. 16.1 mm [p < 0.001] and 109.0 vs. 160.8 mm² [p = 0.005], respectively). The tentorial angle was also steeper in children with achondroplasia (mean 47.6 vs. 38.1 degrees; p < 0.001), while the clivus was significantly shorter (mean 23.5 vs. 30.3 mm; p < 0.001). Significant differences were also observed in myelon area, occipital angle, fourth ventricle, intracranial cerebrospinal fluid and supratentorial ventricular volumes, and the volume of brainstem protruding beyond the posterior fossa (all p < 0.05). MRI analysis of brain structures may provide a standardized value to indicate decompression surgery in children with achondroplasia. Full article

Background: Adults with achondroplasia face physical and psychosocial challenges that may impact their health-related quality of life and mental health. This exploratory cross-sectional study aimed to investigate relationships between health-related quality of life, mental health, and physical activity levels in adults with achondroplasia, focusing on potential gender differences. Methods: Sixteen adults with achondroplasia (10 women, 6 men; age 37.2 ± 13.5 years) completed the Short Form Health survey, the Brief Symptom Inventory, and the International Physical Activity questionnaire. Descriptive statistics, non-parametric group comparisons, correlational analyses, and linear regressions were conducted. Results: Moderate physical activity showed strong positive correlations with general health (rs = 0.79, 95% CI [0.50, 0.92]), vitality (rs = 0.60, 95% CI [0.15, 0.85]), and physical functioning (rs = 0.62, 95% CI [0.18, 0.86]), on SF-36. Women reported lower quality of life scores than men across most SF-36 dimensions. Significant gender difference was observed in vitality (r = 0.61) and pain (r = 0.55). Physically active participants presented better outcomes in general health (r = 0.63) and vitality (r = 0.55) compared to inactive participants. Conclusions: This study provides preliminary evidence suggesting potential benefits of moderate-intensity physical activity on health-related quality of life and mental health among adults with achondroplasia, with notable gender differences. While limited by sample size and study design, the findings highlight the need for larger, longitudinal studies to further explore the role of physical activity in enhancing well-being in this population. Full article

Background: Achondroplasia is a genetic condition that results in several orofacial and physical manifestations that predispose patients to dental, breathing, and sleep issues. Case Description: This report details the case of a 2-year-old girl with achondroplasia, malocclusion, speech and breathing dysfunction, and obstructive sleep apnea (OSA). Treatment involved using a myofunctional device that required chewing twice per day, two simple tongue exercises, speech-language therapy, chiropractic therapy, and continuous positive airway pressure (CPAP) for 24 months. Throughout the treatment period, the patient demonstrated significant improvements in her sleep, breathing, dental occlusion, speech, and overall confidence. Conclusion: This case report highlights how pediatric patients with achondroplasia can improve their OSA symptoms and health with conservative myofunctional therapy interventions.
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Introduction: A plethora of biological molecules regulate chondrogenesis in the epiphyseal growth plate. Disruptions of the quantity and function of these molecules can manifest clinically as stature abnormalities of various etiologies. Traditionally, the growth hormone/insulin-like growth factor 1 (IGF1) axis represents the etiological centre of final stature attainment. Of note, little is known about the molecular events that dominate the growth of the craniofacial complex and its correlation with somatic stature. Aim: Given the paucity of relevant data, this review discusses available information regarding potential applications of lateral cephalometric radiography as a potential clinical indicator of genetic short stature in children. Materials and Methods: A literature search was conducted in the PubMed electronic database using the keywords: cephalometric analysis and short stature; cephalometric analysis and achondroplasia; cephalometric analysis and hypochondroplasia; cephalometric analysis and skeletal abnormalities; cephalometr* and SHOX; cephalometr* and CNP; cephalometr* and ACAN; cephalometr* and CNVs; cephalometr* and IHH; cephalometr* and FGFR3; cephalometr* and Noonan syndrome; cephalometr* and “Turner syndrome”; cephalometr* and achondroplasia. Results: In individuals with genetic syndromes causing short stature, linear growth of the craniofacial complex is confined, following the pattern of somatic short stature regardless of its aetiology. The angular and linear cephalometric measurements differ from the measurements of the average normal individuals and are suggestive of a posterior placement of the jaws and a vertical growth pattern of the face. Conclusions: The greater part of the existing literature regarding cephalometric measurements in short-statured children with genetic syndromes provides qualitative data. Furthermore, cephalometric data for individuals affected with specific rare genetic conditions causing short stature should be the focus of future studies. These quantitative data are required to potentially establish cut-off values for reference for genetic testing based on craniofacial phenotypes. Full article

Background: Achondroplasia, the most prevalent skeletal dysplasia, stems from a functional mutation in the fibroblast growth factor receptor 3 gene, leading to growth impairment. This condition presents multifaceted medical, functional and psychosocial challenges throughout childhood, adolescence and adulthood. Current management strategies aim to minimise medical complications, optimise functional capabilities and provide comprehensive supportive care. Vosoritide (trade name: VOXZOGO^®, BioMarin Pharmaceuticals) is the first disease-modifying pharmaceutical treatment approved for the management of patients with achondroplasia and became available in Australia in May 2023. Methods: Standardised clinical guidelines for its optimal use are not yet widely available. To address this gap, a multidisciplinary Australian Vosoritide Working Group, comprising 12 experts with experience in achondroplasia management from across Australia, developed recommendations to guide the use of vosoritide in clinical practice. Results: The recommendations, which are expert opinions of the Australian Vosoritide Working Group, aim to (i) standardise the use of vosoritide across Australia, (ii) support the safe clinical rollout of vosoritide and (iii) support universal access. Conclusions: These recommendations have been developed for healthcare professionals and institutions that are engaged in using vosoritide in the management of achondroplasia and will be revised using a formal framework for clinical guideline development once more evidence is available. Full article

Background: Achondroplasia is a rare genetic disease, yet the most common form of dwarfism, characterized by limb shortening and disproportionate short stature along with musculoskeletal changes, such as postural deviations. Although postural changes in the spine in children with achondroplasia have been well investigated, little is known about the association of achondroplasia with spinal movements/mobility. Methods: This preliminary study aims to explore the association of achondroplasia with spinal mobility in children with achondroplasia compared to age- and sex-matched healthy individuals. Spinal posture and mobility were assessed using a radiation-free back scan, the Idiag M360 (Idiag, Fehraltorf, Switzerland). Between-group differences were determined using a two-way analysis of variance. Results: Children with achondroplasia had smaller thoracic lateral flexion [difference between groups (Δ) = 20.4°, 95% CI 0.1°–40.6°, p = 0.04], lumbar flexion (Δ = 17.4°, 95% CI 5.5°–29.4°, p = 0.006), lumbar extension (Δ = 14.2°, 95% CI 5.7°–22.8°, p = 0.002) and lumbar lateral flexion (Δ = 19.6°, 95% CI 10.7°–28.4°, p < 0.001) than age- and sex-matched healthy individuals, except for thoracic extension (Δ = 16.5°, 95% CI 4.4°–28.7°, p = 0.009) which was greater in children with achondroplasia. No differences were observed in global spinal postures between the two groups. Conclusions: Spinal mobility appears to be more influenced by achondroplasia than global spinal postures in childhood. These results also highlight the importance of considering the musculoskeletal assessment of segmental spinal postures and rehabilitative interventions aimed at promoting spinal flexibility in children with achondroplasia. Full article

Background: Achondroplasia is a rare genetic skeletal condition characterized by disproportionate short stature. There is limited evidence on postural control in adults with achondroplasia and how lower limb lengthening (intervention) interacts with body dynamics. This study investigated sway variability during quiet standing in adults with achondroplasia with natural growth (N) and with lower limb lengthening (LL). Methods: Sixteen adults performed bilateral/unilateral standing tasks. Linear (total excursion, amplitude, and ellipse area) and nonlinear (sample entropy and correlation dimension) center of pressure sway metrics were analyzed in the anteroposterior/mediolateral directions. Relationships between posture metrics, strength, and physical activity were explored. Between-groups statistics were calculated. Results: The LL group exhibited amplified linear sway, indicating larger postural deviations, and reduced sample entropy and correlation dimension, indicative of more rigid and repeated corrections. The N group exhibited more unpredictable and adaptive movement corrections. Numerous correlations emerged between strength and posture measures, with relationships altered by intervention. Conclusions: Adults with achondroplasia display distinct balance strategies influenced by intervention. The results indicate that LL is associated with altered variability and adaptability compared to natural development. Relationships with muscle strength spotlight a key role of muscle capacity in postural control modulation after growth alterations in this population. Full article

Skeletal dysplasia, also called osteochondrodysplasia, is a category of disorders affecting bone development and children’s growth. Up to 552 genes, including fibroblast growth factor receptor 3 (FGFR3), have been implicated by pathogenic variations in its genesis. Frequently identified causal mutations in osteochondrodysplasia arise in the coding sequences of the FGFR3 gene: c.1138G>A and c.1138G>C in achondroplasia and c.1620C>A and c.1620C>G in hypochondroplasia. However, in some cases, the diagnostic investigations undertaken thus far have failed to identify the causal anomaly, which strengthens the relevance of the diagnostic strategies being further refined. We observed a Caucasian adult with clinical and radiographic features of achondroplasia, with no common pathogenic variant. Exome sequencing detected an FGFR3(NM_000142.4):c.1075+95C>G heterozygous intronic variation. In vitro studies showed that this variant results in the aberrant exonization of a 90-nucleotide 5′ segment of intron 8, resulting in the substitution of the alanine (Ala359) for a glycine (Gly) and the in-frame insertion of 30 amino acids. This change may alter FGFR3’s function. Our report provides the first clinical description of an adult carrying this variant, which completes the phenotype description previously provided in children and confirms the recurrence, the autosomal-dominant pathogenicity, and the diagnostic relevance of this FGFR3 intronic variant. We support its inclusion in routinely used diagnostic tests for osteochondrodysplasia. This may increase the detection rate of causal variants and therefore could have a positive impact on patient management. Finally, FGFR3 alteration via non-coding sequence exonization should be considered a recurrent disease mechanism to be taken into account for new drug design and clinical trial strategies. Full article

Advanced paternal age increases the risk of transmitting de novo germline mutations, particularly missense mutations activating the receptor tyrosine kinase (RTK) signalling pathway, as exemplified by the FGFR3 mutation, which is linked to achondroplasia (ACH). This risk is attributed to the expansion of spermatogonial stem cells carrying the mutation, forming sub-clonal clusters in the ageing testis, thereby increasing the frequency of mutant sperm and the number of affected offspring from older fathers. While prior studies proposed a correlation between sub-clonal cluster expansion in the testis and elevated mutant sperm production in older donors, limited data exist on the universality of this phenomenon. Our study addresses this gap by examining the testis-expansion patterns, as well as the increases in mutations in sperm for two FGFR3 variants—c.1138G>A (p.G380R) and c.1948A>G (p.K650E)—which are associated with ACH or thanatophoric dysplasia (TDII), respectively. Unlike the ACH mutation, which showed sub-clonal expansion events in an aged testis and a significant increase in mutant sperm with the donor’s age, as also reported in other studies, the TDII mutation showed focal mutation pockets in the testis but exhibited reduced transmission into sperm and no significant age-related increase. The mechanism behind this divergence remains unclear, suggesting potential pleiotropic effects of aberrant RTK signalling in the male germline, possibly hindering differentiation requiring meiosis. This study provides further insights into the transmission risks of micro-mosaics associated with advanced paternal age in the male germline. Full article

This paper presents a rare case of fetal hydrops detected at just 23 weeks of gestation in a 22-year-old woman’s first pregnancy. The fetal ultrasound revealed severe skeletal anomalies, craniofacial deformities, and thoracic abnormalities, suggesting a complex and severe skeletal dysplasia, potentially type IA Achondrogenesis—a lethal autosomal recessive condition marked by ossification delay. This case highlights the significance of advanced genetic testing, such as next-generation sequencing (NGS) and whole-genome sequencing (WGS), in diagnosing and understanding skeletal dysplasias. Skeletal dysplasias represent a group of genetic disorders that affect osteogenesis. The prevalence of this condition is 1 in 4000 births. Sadly, 25% of affected infants are stillborn, and around 30% do not survive the neonatal period. There is a wide range of rare skeletal dysplasias, each with its own specific recurrence risk, dysmorphic expression, and implications for neonatal survival and quality of life. When skeletal dysplasia is incidentally discovered during routine ultrasound screening in a pregnancy not known to be at risk of a specific syndrome, a systematic examination of the limbs, head, thorax, and spine is necessary to reach the correct diagnosis. Prenatal diagnosis of skeletal dysplasia is crucial for providing accurate counselling to future parents and facilitating the proper management of affected pregnancies. An accurate diagnosis can be a real challenge due to the wide spectrum of clinical presentations of skeletal dysplasia but advances in imaging technologies and molecular genetics have improved accuracy. Additionally, some of these skeletal dysplasias may present clinical overlap, making it especially difficult to distinguish. After the 11th revision of genetic skeletal disorder nosology, there are 771 entities associated with 552 gene mutations. The most common types of skeletal dysplasia are thanatophoric dysplasia, osteogenesis imperfect, achondroplasia, achondrogenesis, and asphyxiating thoracic dystrophy. Full article