Evaluation of functionality-mobility in patients with skeletal dysplasias. Application of the STEMS tool ("everyday symptoms and mobility screening tool for skeletal dysplasias").

Individuals with differing forms of skeletal dysplasias (SD) frequently report impaired mobility and symptoms. With the objetive to evaluate mobility and associated symptoms in people with SD at an Argentinian pediatric hospital, using an Argentinian version of the Screening Tool for Everyday Mobility and Symptoms (STEMS), a simple questionnaire that allows clinicians to quickly identify the presence of symptoms associated with mobility in people with SD, while considering different environmental settings and the use of assistive devices, an analytical study of a consecutive sample of patients older than 5 years with SD and their affected relatives was carried out.Diagnosis, comorbidities, socioenvironmental, therapeutic, auxological and mobility variables were recorded. The presence and intensity of symptoms was noted through use of both the STEMS and validated scales. Descriptive, association and correlation analyzes were performed. One hundred and nineteen individuals with SD were enrolled in the study and divided into groups: Osteogenesis Imperfecta (OI, n = 55), Achondroplasia (ACH, n = 36) and Other SD resulting in disproportionate short stature (n = 28). Mobility assistive devices were almost exclusively used by individuals with OI. They were more frequently used by individuals with overweight and obesity, more severe form of the disease and in the outdoor settings. Two thirds (66.4%) of the individuals assessed in this study reported pain, 87.4% reported fatigue, and 58.8% reported both pain and fatigue. The intensity of symptoms was similar between groups and correlated with age and auxological variables. The STEMS was clear, easy and quick to use for identifying presence of pain and fatigue in this population group. The STEMS proved to be a simple and useful tool for evaluating functional mobility and associated symptoms in our population of individuals with SD.

Alteration of major venous drainage routes in a patient with achondroplasia after ventriculoperitoneal shunt placement.

Achondroplasia is the most common form of dwarfism, caused by a mutation in fibroblast growth factor receptor 3 gene, leading to multiple pathological conditions. Herein, we present a case of an infant with achondroplasia associated with hydrocephalus and severe foramen magnum stenosis. Computed tomography (CT) venography showed prominent suboccipital emissary veins comprising major venous drainage routes and hypoplastic transverse sinuses, which increased the risk of foramen magnum decompression. The infant was initially treated with ventriculo-peritoneal (VP) shunt. After 8 months, CT venography showed regression of suboccipital emissary veins and more prominent transverse sinuses. Subsequently, foramen magnum decompression was safely performed without sacrificing major venous drainage routes.

Surgical outcome after treatment of thoracolumbar spinal stenosis in adults with achondroplasia.

PURPOSE: To describe the complications and the outcome of patients with achondroplasia undergoing thoracolumbar spinal surgery. METHODS: Retrospective analysis of prospectively collected data of all patients with achondroplasia undergoing surgery within the years 1992-2021 at the thoracic and/or lumbar spine. The outcome was measured by analyzing the surgical complications and revisions. The patient-rated outcome was assessed with the COMI score from 2005 onwards. RESULTS: A total of 15 patients were included in this study undergoing a total of 31 surgeries at 79 thoracolumbar levels. 12/31 surgeries had intraoperative complications consisting of 11 dural tears and one excessive intraoperative bleeding. 4/18 revision surgeries were conducted due to post-decompression hyperkyphosis. The COMI score decreased from 7.5 IQR 1.4 (range 7.1-9.8) preoperatively to 5.3 IQR 4.1 (2.5-7.5) after 2 years (p = 0.046). CONCLUSION: Patients with achondroplasia, the most common skeletal dysplasia condition with short-limb dwarfism, are burdened with a congenitally narrow spinal canal and are commonly in need of spinal surgery. However, surgery in these patients is often associated with complications, namely dural tears and post-decompression kyphosis. Despite these complications, patients benefit from surgical treatment at a follow-up of 2 years after surgery.

Prophylactic Intramedullary Rodding After Femoral Lengthening in Patients With Achondroplasia and Hypochondroplasia.

BACKGROUND: Femoral fracture after femoral lengthening in patients with achondroplasia and hypochondroplasia is a frequent complication, occurring in up to 30%. The purpose of this study is to demonstrate the effectiveness of prophylactic intramedullary rodding in preventing this complication. METHODS: Multicenter retrospective study involving 86 femoral lengthening procedures in 43 patients with achondroplasia or hypochondroplasia. Forty-two femora (21 patients) were prophylactically managed with intramedullary Rush rodding after external fixation removal (11 females and 10 males, mean age 14.6 years) compared with 44 femora (22 patients) without prophylactic intramedullary rodding (13 females and 9 males, mean age 15.2 years). The mean amount of lengthening in the rodding group was 13.3 cm (52.6%) with an External Fixation Index of 25.8 days/cm; in patients without rodding was 14.3 cm (61.5%) and 24.5 days/cm, respectively. RESULTS: Seven cases (15.9%) without rodding developed fractures. Four of them required surgical correction due to displacement or shortening. Only 1 patient (2.4%) had fracture of the femur after prophylactic rodding, and surgery was not required. The incidence of femur fracture was significantly lower in the prophylactic rodding group compared with the nonrodding group (2.4% vs. 15.9%, respectively; P =0.034). There were no cases of infection or avascular necrosis. CONCLUSIONS: Prophylactic intramedullary rodding is a safe and effective method for preventing femoral fractures after femoral lengthening in patients with achondroplasia or hypochondroplasia. LEVEL OF EVIDENCE: Level III-a retrospective comparative study.

Surgery for Spinal Stenosis in Achondroplasia: Causes of Reoperation and Reduction of Risks.

BACKGROUND: Individuals with achondroplasia are prone to symptomatic spinal stenosis requiring surgery. Revision rates are thought to be high; however, the precise causes and rates of reoperation are unknown. The primary aim of this study is to investigate the causes of reoperation after initial surgical intervention in individuals with achondroplasia and spinal stenosis. In addition, we report on surgical techniques aimed at reducing the risks of these reoperations. METHODS: A retrospective review was conducted over an 8-year period of all patients with achondroplasia at a single institution that serves as a large referral center for patients with skeletal dysplasias. Patients with achondroplasia who underwent spinal surgery for stenosis were identified and the need for revision surgery was studied. Data collected included demographic, surgical, and revision details. Fisher exact test was used to determine if an association existed between construct type and the need for revisions. RESULTS: Thirty-three of the 130 (22%) patients with achondroplasia required spinal stenosis surgery. Twenty-four individuals who met the criteria were selected for analysis. The initial spine surgery was at an average age of 18.7 years (SD: 10.1 y). Nine patients (38%) required revision surgeries, and 3 required multiple revisions. Five of 9 (56%) of the revisions had primary surgery at an outside institution. Revision surgeries were due to caudal pseudarthrosis (the distal instrumented segment) (8), proximal junctional kyphosis (PJK) (7), and new neurological symptoms (7). There was a significant association found between construct type and the need for revision ( P =0.0111). The pairwise comparison found that short fusions were significantly associated with the need for revision compared with the interbody group ( P =0.0180). PJK was associated with short fusions when compared with the long fusion group ( P =0.0294) and the interbody group ( P =0.0300). Caudal pseudarthrosis was associated with short fusions when compared with the interbody group ( P =0.0015). Multivariate logistic regression found long fusion with an interbody was predictive of and protective against the need for revision surgery ( P =0.0246). To date, none of the initial cases that had long fusions with caudal interbody required a revision for distal pseudarthrosis. CONCLUSIONS: In patients with achondroplasia, the rate of surgery for spinal stenosis is 22% and the risk of revision is 38% and is primarily due to pseudarthrosis, PJK, and recurrent neurological symptoms. Surgeons should consider discussing spinal surgery as part of the patient's life plan and should consider wide decompression of the stenotic levels and long fusion with the use of an interbody cage at the caudal level in all patients to reduce risks of revision. LEVEL OF EVIDENCE: Level IV-Retrospective case series.

Evaluation of simultaneous bilateral femoral distraction osteogenesis with antegrade intramedullary lengthening nails in achondroplasia with rhizomelic short stature: a retrospective study of 15 patients with a minimum follow-up of 2 years.

BACKGROUND AND PURPOSE: Bilateral femoral distraction osteogenesis in patients with achondroplasia is insufficiently reported. We aimed to perform the first study that exclusively analyzed simultaneous bilateral femoral distraction osteogenesis with motorized intramedullary lengthening nails via an antegrade approach in patients with achondroplasia focused on reliability, accuracy, precision, and the evolving complications. PATIENTS AND METHODS: In this retrospective singlecenter study we analyzed patients with achondroplasia who underwent simultaneous bilateral femoral lengthening with antegrade intramedullary lengthening nails between October 2014 and April 2019. 15 patients (30 femoral segments) of median age 14 years (interquartile range [IQR] 12-15) were available for analysis. The median follow-up was 29 months (IQR 27-37) after nail implantation. RESULTS: The median distraction length per segment was 49 mm (IQR 47-51) with a median distraction index of 1.0 mm/day (IQR 0.9-1.0), and a median consolidation index of 20 days/cm (IQR 17-23). Reliability of the lengthening nails was 97% and their calculated accuracy and precision were 96% and 95%, respectively. The most common complication was temporary restriction of knee range of motion during distraction in 10 of 30 of the lengthened segments. 1 patient was treated with 2 unplanned additional surgeries due to premature consolidation. CONCLUSION: The method is reliable and accurate with few complications.

Route of delivery does not impact postnatal surgical morbidity in pregnancies affected by fetal achondroplasia.

PURPOSE: Pregnancies affected by maternal or fetal achondroplasia present unique challenges. The optimal route of delivery in fetuses with achondroplasia has not been established. Our objective was to determine whether the route of delivery affects postnatal achondroplasia-related surgical burden. METHODS: We conducted a secondary analysis of Achondroplasia Natural History Study (CLARITY), which is a multicenter natural history cohort study of patients with achondroplasia. Achondroplasia-related surgical morbidity, which we defined as the need for one or more postnatal achondroplasia-related surgeries, was assessed in relation to the route of delivery and whether the mother also had achondroplasia. Rate of each individual surgery type (otolaryngology, brain, foramen magnum, spine, and extremity) was also assessed in relation to the route of delivery. RESULTS: Eight hundred fifty-seven patients with achondroplasia with known route of delivery and known maternal stature were included. Three hundred sixty (42%) patients were delivered vaginally, and 497 (58%) patients were delivered by a cesarean delivery. There was no difference in the odds of requiring any postnatal achondroplasia-related surgery in those with achondroplasia who were delivered vaginally compared with those delivered by cesarean birth (odds ratio 0.95, 95% CI = 0.68-1.34, P = .80). No difference was present in the odds of requiring any postnatal achondroplasia-related surgery when route of delivery was compared for fetuses born to 761 average stature mothers (odds ratio 1.05, 95% CI = 0.74-1.51, P = .78). There was also no difference in the odds of requiring each of the individual achondroplasia-related surgeries by route of delivery, including cervicomedullary decompression. CONCLUSION: Our study suggests that it is reasonable for average stature patients carrying a fetus with achondroplasia to undergo a trial of labor in the absence of routine obstetric contraindications.

Assessment of body fat mass, anthropometric measurement and cardiometabolic risk in children and adolescents with achondroplasia and hypochondroplasia.

Achondroplasia is a rare skeletal dysplasia characterized by rhizomelic short stature, whose prevalence is about 1 per 25,000 births. For some patients with achondroplasia, excess body weight is one of the major concerns due to an impaired linear growth. Epidemiological studies revealed a premature onset of cardiovascular or cerebrovascular events in achondroplasia. An association between obesity and cardiometabolic risk factors related to cardiovascular events remains unknown in patients with achondroplasia/hypochondroplasia. This cross-sectional study investigated anthropometric measurements, body compositions and cardiometabolic risk factors in pediatric patients with achondroplasia/hypochondroplasia. Thirty-two patients with achondroplasia and ten with hypochondroplasia aged between 1.9 and 18.7 years were enrolled in this study. Half of the participants presented at least one cardiometabolic abnormality. Elevated systolic blood pressure was the most common abnormality. None of the participants developed metabolic syndrome or type 2 diabetes mellitus. Body mass index-standard deviation score and hip/height ratio were strongly correlated with percent body fat assessed by dual energy X-ray absorptiometry although no significant association was found between anthropometric measurements or body fat mass and any cardiometabolic risk factors. No significant difference in body fat mass, as well as body mass index-standard deviation score and hip/height, was found between cardiometabolically normal group and cardiometabolically abnormal groups. These results suggest that not only weight gain and hip/height changes should be monitored but also individual cardiometabolic risk factors should be evaluated to avoid cardiometabolic events in the healthcare management of pediatric patients with achondroplasia/hypochondroplasia.

Spinal canal stenosis in children with achondroplasia: the role of augmentation laminoplasty-a 15-year single institution experience.

PURPOSE: Achondroplasia typically results in compressive spinal canal stenosis in one-third of children, but rare under the age of 15 years. Laminectomy is the mainstay of treatment but this leads to instability and progressive deformity requiring complex fixation. In order to reduce that risk, we developed a novel modified augmented laminoplasty that increases spinal canal diameter while preserving the posterior column stability. METHODS: All laminoplasty cases for spinal compressive achondroplasia from 2006 to 2020 were included. Ten augmentation laminoplasty procedures were performed in 7 children with regular clinical and radiological post-operative follow-up. Kyphotic deformity and clinical outcomes (neurological and urological) were evaluated. RESULTS: At presentation, clinical features included radiculopathy, neurogenic claudication or acute cauda equina compression with sphincter dysfunction. The average age at initial surgery was 11.2 (range 5-16) with a mean follow-up of 5 (range 2-8) years. All patients demonstrated improvement in neurogenic claudication symptoms after surgery; however, bladder dysfunction persisted in some children. In one child, cervical and lumbar augmentation laminoplasties were performed for concomitant disease. Augmentation laminoplasty effectively prevented deformity progression over time in all cases except one where a further revision laminoplasty with extension was required for screw loosening. Despite this, progressive symptomatic kyphotic deformity led to a 360° fixation. Minor complications included one dural breach (repaired intraoperatively) and one superficial wound infection. CONCLUSION: Augmentation laminoplasty is a viable surgical option following laminectomy in achondroplasia patients as an alternative to surgical fixation. Fixation can be reserved for cases where there is progressive deformity and kyphosis.

Unravelling the pathogenesis of foramen magnum stenosis in patients with severe achondroplasia: a CT-based comparison with age-matched controls and FGFR3 craniosynostosis syndromes.

OBJECTIVE: Foramen magnum(FM) stenosis can be responsible for acute and chronic damage to the cervicomedullary junction in children with achondroplasia. The bony anatomy and patterns of suture fusion of the FM in this context are incompletely understood, yet becoming increasingly important in the light of novel medical therapies for achondroplasia. The objective of this study was to describe and quantify bony anatomy and fusion patterns of FM stenosis in patients with achondroplasia using CT scans, comparing them to age-matched controls and other FGFR3 craniosynostosis patients. METHODS: Patients with achondroplasia and severe FM stenosis, classified as achondroplasia foramen magnum score(AFMS) grades 3 and 4, were identified from a departmental operative database. All had pre-operative CT scans of the craniocervical junction. Measurements obtained comprised sagittal diameter (SD), transverse diameter (TD), foramen magnum area, and opisthion thickness. Anterior and posterior interoccipital synchondroses (AIOS and PIOS) were graded by the extent of fusion. These measurements were then compared with CT scans from 3 age-matched groups: the normal control group, children with Muenke syndrome, and children with Crouzon syndrome with acanthosis nigricans (CSAN). RESULTS: CT scans were reviewed in 23 cases of patients with achondroplasia, 23 normal controls, 20 Muenke, and 15 CSAN. Children with achondroplasia had significantly smaller sagittal diameter (mean 16.2 ± 2.4 mm) compared to other groups (control 31.7 ± 2.4 mm, p < 0.0001; Muenke 31.7 ± 3.5 mm, p < 0.0001; and CSAN 23.1 ± 3.4 mm, p < 0.0001) and transverse diameters (mean 14.3 ± 1.8 mm) compared with other groups (control 26.5 ± 3.2 mm, p < 0.0001; Muenke 24.1 ± 2.6 mm, p < 0.0001; CSAN 19.1 ± 2.6 mm, p < 0.0001). This translated into a surface area which was 3.4 times smaller in the achondroplasia group compared with the control group. The median grade of the AIOS fusion achondroplasia group was 3.0 (IQR 3.0-5.0), which was significantly higher compared with the control group (1.0, IQR 1.0-1.0, p < 0.0001), Muenke group (1.0, IQR 1.0-1.0, p < 0.0001), and CSAN (2.0, IQR 1.0-2.0, p < 0.0002). Median PIOS fusion grade was also highest in the achondroplasia group (5.0, IQR 4.0-5.0) compared with control (1.0, IQR 1.0-1.0, p < 0.0001), Muenke (2.5, IQR 1.3-3.0, p < 0.0001), and CSAN (4.0, IQR 4.0-4.0, p = 0.2). Distinct bony opisthion spurs projecting into the foramen magnum were seen in achondroplasia patients but not others, resulting in characteristic crescent and cloverleaf shapes. CONCLUSION: Patients with AFMS stages 3 and 4 have significantly reduced FM diameters, with surface area 3.4 times smaller than age-matched controls. This is associated with premature fusion of the AIOS and PIOS in comparison with controls and other FGFR3-related conditions. The presence of thickened opisthion bony spurs contributes to stenosis in achondroplasia. Understanding and quantifying bony changes at the FM of patients with achondroplasia will be important in the future quantitative evaluation of emerging medical therapies.

Midline-Sparing Interapophysealaminar Decompression Technique for Management of Lumbar Stenosis in Pediatric Achondroplasia.

INTRODUCTION: Achondroplasia is the most common form of short-limb dwarfism in humans, with an incidence of 1 in 25,000-40,000 live births. About one-third of achondroplasia patients will require operative intervention for lumbar spinal stenosis, generally presenting with progressive neurogenic claudication. The anatomy of the achondroplastic lumbar spine, with shortened pedicles, hypertrophic zygapophyseal joints, and thickened laminae frequently results in the development of multilevel interapophyseolaminar stenosis, while stenosis is usually absent at the mid-laminar levels secondary to pseudo-scalloping of the vertebral bodies. Treatment remains controversial, as disrupting the posterior tension band with complete laminectomies in the pediatric population puts patients at risk of developing post-laminectomy kyphosis. CASE PRESENTATION: A 15-year-old girl with achondroplasia presented to clinic with debilitating neurogenic claudication in the setting of multilevel lumbar interapophyseolaminar stenosis. We present a technical case report of her successful surgical treatment using a midline posterior tension band sparing modification to the interapophyseolaminar decompression technique proposed by Thomeer et al. [J Neurosurg. 2002;96(3 Suppl l):292-7]. CONCLUSION: We demonstrate that an adequate interapophyseolaminar decompression can be achieved through the performance of bilateral laminotomies, bilateral medial facetectomies, and undercutting of the ventral spinous process while preserving supraspinous and interspinous ligament attachments. Given the generally multilevel nature of lumbar stenosis and longer life expectancies of pediatric achondroplasia patients, decompressive surgical interventions must aspire to minimize disruption of spine biomechanics if fusion surgery is to be avoided.

Growth Modulation by Tension Band Plate in Achondroplasia With Varus Knee Deformity: Comparison of Gait Analysis Measurements.

BACKGROUND: Limited evidence exists concerning growth modulation by tension band plate (TBP) to correct varus deformity in patients with achondroplasia with limited growth due to FGFR3 gene mutation. We evaluated the efficacy of TBP in children with achondroplasia with genu varum and reported the static radiographic and dynamic motion data to determine parameters that impact the rate of deformity correction. METHODS: Patients with achondroplasia with genu varum who underwent TBP surgery for growth modulation were studied. Those with at least 1 year of follow-up with TBP were included. Radiographic parameters were measured. Growth velocity of femoral/tibial length was calculated separately. Patients were deemed successful or unsuccessful. Spearman correlation analysis and Student t test were used to describe statistical results. RESULTS: Twenty-two patients (41 limbs; 12 girls) fulfilled our criteria. Mean age at TBP surgery was 7.6±2.4 years. Thirty-six femoral TBP and 41 tibial TBP were in place for 24.5±9.7 months. Mean mechanical axis deviation, mechanical lateral distal femoral angle, and medial proximal tibial angle preoperatively were 30.1±7.6 mm, 97.2±6.4, and 80.3±4.3 degrees, and 11±15.6 mm, 87.4±5.9, and 84.7±5.3 degrees at last follow-up ( P <0.001). Fifteen limbs were successfully straightened; 4 limbs were in more varus than the initial deformity. Twenty-four limbs with TBP were still undergoing correction. In successful limbs, mean age at surgery was 6.5±1.7 years and duration of TBP was 29.9±7.8 months. In 4 unsuccessful limbs, mean age at surgery was 11.7±1.2 years. Analysis in the gait laboratory included physical examination with the measurement of knee varus and kinematic varus based on a posterior view static standing photograph. Photographic measurement of varus was higher than the radiographic measurement. CONCLUSIONS: Growth modulation by TBP surgery is a reliable and simple technique to correct genu varum in achondroplasia. An early age at TBP implementation (mean: 6.5 y) is crucial to successfully correct the varus knee deformity. Furthermore, we recommend early and regular surveillance of achondroplasia for progressive varus knee deformity. LEVEL OF EVIDENCE: Level IV-cohort study.

Hemiepiphysiodesis for Lower Extremity Coronal Plane Angular Correction in the Distal Femur and Proximal Tibia in Children With Achondroplasia.

BACKGROUND: Achondroplasia is the most prevalent form of skeletal dysplasia, affecting more than 250,000 individuals. Lower extremity angular deformities, particularly genu varum, are common in children with achondroplasia, often resulting in pain and limitation of function. The authors aim to determine the utility of lower extremity growth modulation with hemiepiphysiodesis in children with achondroplasia for correction of coronal plane deformities about the knee. METHODS: The authors performed a retrospective chart review of a single center from 1/1/2000 to 12/31/2020 to identify pediatric patients with achondroplasia treated with hemiepiphysiodesis as their initial procedure at the distal femur and/or proximal tibia. Patients with adequate records and who had completed their treatment were included. Data collected included duration of treatment, complications, need for osteotomy, and radiographic measurements including initial and final mechanical axis deviation, knee mechanical axis zone, mechanical lateral distal femoral angle and medial proximal tibia angle. RESULTS: Ten patients with 17 limbs met our criteria. Nine patients (15 limbs) were treated for genu varum and 1 patient (2 limbs) was treated for genu valgum. Prior to treatment, the mechanical axis fell in zone 3 in 59% of limbs and zone 2 in 41%. Average correction in mechanical axis deviation was 26.1 mm. Average change in mechanical lateral distal femoral angle was 10.3 degrees per limb, and average change in medial proximal tibia angle was 7.1 degrees per limb. Average treatment duration was 909 days. At final follow up, 81% (14/17) of limbs had the mechanical axis in zone 1, with the remaining 18% (3/17) in zone 2. No patient/limb underwent subsequent distal femur or proximal tibia osteotomy for coronal plane alignment. CONCLUSIONS: Children with achondroplasia can successfully be treated with hemiepiphysiodesis to correct coronal plane deformities at the distal femur and proximal tibia. Using this technique, no patient in our series required an osteotomy for genu varum/valgum. LEVEL OF EVIDENCE: Therapeutic level IV, Case series.

Cranio-cervical junction malformation causing cord compression in infant with achondroplasia: a bigger picture.

INTRODUCTION: Achondroplasia is a genetic disorder known for short stature and skeletal abnormalities. CASE REPORT: We present a case of narrowing of the foramen magnum from a large opisthion extending to the spinal canal. CONCLUSION: Foramen magnum stenosis and cervicomedullary stenosis are potentially life threatening neurological manifestations of achondroplasia.

Centrally mediated obstructive apnoea and restenosis of the foramen magnum in an infant with achondroplasia.

Achondroplasia is associated with foramen magnum stenosis. We report a male infant with achondroplasia and centrally mediated obstructive apnoea who underwent two foramen magnum decompression due to bone regrowth. He presented at six weeks of age with breath holding and apnoeic episodes associated with significant desaturation, requiring non-invasive ventilation. Craniospinal imaging revealed a narrow foramen magnum without signal change in the spinal cord. Sleep studies showed obstructive, but not central, apnoea. Respiratory abnormalities persisted and reimaging at two months showed development of significant signal changes at the cervicomedullary junction (CMJ). He underwent emergency foramen magnum decompression with initial clinical improvement. Ten days later he relapsed with further apnoeic episodes requiring respiratory support. After extensive re-investigations including CT and MRI, incomplete initial decompression and foramen magnum restenosis were considered and confirmed with a CT head scan 15 weeks after the initial operation. Repeat decompression of bone and removal of thickened dural bands resulted in complete resolution of the apnoeic episodes. Obstructive sleep apnoea can be centrally mediated and further decompression of foramen magnum stenosis should be considered, especially if significant respiratory compromise persists or recurs.

Disease-specific complications and multidisciplinary interventions in achondroplasia.

Achondroplasia (ACH) is the most common skeletal dysplasia and characterized by a disproportionate short stature, macrocephaly with frontal bossing, exaggerated lumbar lordosis, and trident hands. It is induced by activated mutations in the fibroblast growth factor receptor 3 (FGFR3) gene. In addition to short stature, patients with ACH have a high prevalence of medical complications, including upper airway obstructive apnea, increased mortality, foramen magnum stenosis, hydrocephalus, developmental delay, recurrent ear infections, genu varum, obesity, and spinal canal stenosis, throughout their whole life. Several investigational drugs that modulate abnormal FGFR3 signaling have recently emerged, vosoritide being the most developed. This review presents the different disease-specific complications of ACH occurring in neonates, infants, childhood, adolescent, and adults and reports the current multidisciplinary interventions for these various complications. Moreover, we propose treatment strategies for children with ACH from the perspective of quality of life in adulthood.

Medical complications in children with achondroplasia.

AIM: To determine the rates of medical investigations, complications, interventions, and outcomes in children with achondroplasia. METHOD: Children and adolescents with achondroplasia born between 2000 and 2019, aged between 0 and 18 years of age, and seen at The Children's Hospital at Westmead skeletal dysplasia clinic were included. Data were collected retrospectively from clinical records. Standard descriptive statistics were used for analysis. RESULTS: The study included 108 participants, 58 males and 50 females. Ninety-nine participants (91.7%) entered the study at birth. The other nine (8.3%) participants entered the study after birth (mean age = 2 years 4 months, SD = 1 year 8 months). The median age of exit from the study was 8 years 8 months (IQR = 8 years 9 months) with a median follow-up of 8 years 8 months (IQR = 8 years 9 months). Fifty-two (48%) participants presented with craniocervical stenosis, 15 (13.9%) with hydrocephalus, 66 (61.1%) with hearing impairment, 44 (40.7%) with sleep-disordered breathing, 46 (42.6%) with lower-limb malalignment, 24 (22.2%) with thoracolumbar kyphosis, 10 (9.3%) with symptomatic spinal stenosis, 12 (11.1%) with obesity, and 16 (14.8%) who had at least one admission for respiratory illness. Two children died during the study period. INTERPRETATION: We report contemporary rates of medical complications in an Australian population of children with achondroplasia. Recommendations for surveillance in clinical practice are discussed. This information will help guide clinicians with their expectant management of achondroplasia and provide prognostic information to the families of children with achondroplasia.

New insights in craniovertebral junction MR changes leading to stenosis in children with achondroplasia.

PURPOSE: To characterize natural history and early changes of craniovertebral junction stenosis in achondroplasia correlating with clinical and radiological outcome. METHODS: Retrospective measures on craniovertebral junction were performed blindly, on sagittal T2-weighted images, in 21 patients with achondroplasia referred from 2008 to 2020. Clinical and polysomnography data were retrospectively collected. Each patient was paired for age and gender with four controls. Wilcoxon means comparison or Student's t-tests were applied. RESULTS: Twenty-one patients (11 females, from 0.1 to 39 years of age) were analyzed and paired with 84 controls. A craniovertebral junction stenosis was found in 11/21 patients (52.4%), all before the age of 2 years. Despite a significant reduction of the foramen magnum diameter (mean ± SD: patients 13.6 ± 6.2 mm, controls 28.5 ± 4.7 mm, p < .001), craniovertebral junction stenosis resulted from the narrowing of C2 dens-opisthion antero-posterior diameter (8.7 ± 3.9 mm vs 24.6 ± 5.1 mm, p < .001). Other significant changes were opisthion anterior placement (-0.4 ± 2.8 mm vs 9.4 ± 2.3 mm, p < .001), posterior tilt of C2 (46.2 ± 13.7° vs 31.6 ± 7.9°, p < .001) and of C1 (15.1 ± 4.3° vs 11.9 ± 5.0°, p = 0.01), and dens thickening (9.4 ± 2.2 mm vs 8.5 ± 2.1 mm, p = 0.03), allowing to define three distinguishable early craniovertebral junction patterns in achondroplasia. All children with C2-opisthion antero-posterior diameter of more than 6 mm had a better clinical and radiological outcome. CONCLUSION: Craniovertebral junction in achondroplasia results from narrowing between C2 dens and opisthion related to anterior placement of opisthion, thickening of C2 dens, and posterior tilt of C1-C2. A threshold of 6 mm for dens-opisthion sagittal diameter seems to correlate with clinical and radiological outcome.

Airways and craniofacial assessment in children affected by achondroplasia with and without sleep-disordered breathing: quantitative magnetic resonance study.

PURPOSE: To identify MRI-based quantitative craniofacial variables linked to airways narrowing and obstructive sleep apnea (OSA) development in children with achondroplasia. METHODS: We evaluated skull base and midface MRI in two cohorts of children affected by achondroplasia, with (group 1) or without OSA (group 2). 3DFSPGR-T1weighted images were used to assess airways volume (nasopharynx, oropharynx, and laryngopharynx), jugular foramina (JF) and hypoglossal foramina (HF) areas, foramen magnum area, cervical cord area, and maxillary retrusion (SNA angle). RESULTS: Nineteen out of 27 children with achondroplasia exhibited different degrees of obstructive respiratory impairment (n.4 mild, n.8 moderate, n.7 severe), while 8 children did not show OSA. Each group was compared with age-matched controls without neuroimaging abnormalities. Both groups showed reduced nasopharynx volume, JF areas, and SNA angle, while group 1 showed also reduced oropharynx volume, ratio of FM/cervical cord areas, and HF areas (p < 0.05). A positive correlation between nasopharynx volume and SNA angle was found in both groups, while a positive correlation among upper airways volume, JF and HF areas was found only in group 1. No correlation between upper airways volume and OSA severity was found. CONCLUSION: In children with achondroplasia, multifaced craniofacial abnormalities contribute to airways volume reduction predisposing to sleep disordered breathing. MRI-based quantitative assessment allows the appraisal of craniofacial variables linked to the development of sleep-disordered breathing such as FM stenosis, jugular and hypoglossal foramina stenosis, and retruded maxillary position and may be a valuable tool for clinical surveillance.

Myasthenia gravis complicating the surgical management of achondroplasia: a case-based update.

BACKGROUND: Achondroplasia is the commonest skeletal dysplasia of autosomal dominant inheritance caused by "gain of function" mutations in the fibroblast growth factor receptor 3 (FGFR3) gene. Foramen magnum compression due to accelerated ossification and spinal canal stenosis secondary to reduced interpedicular distance is a hallmark of achondroplasia, driven by G380R nucleotide pair substitution. In severe cases, limb weakness and neurogenic claudication will require surgical decompression. Rarely, a neurological condition may mimic the compressive spinal dysfunction and therefore, non-surgical causes must also be considered in cases of acute neurological deterioration in children with achondroplasia. Myasthenia gravis (MG) is an autoimmune condition resulting in fatigable muscle weakness. There are no reported cases of myasthenia gravis in achondroplasia in the literature. RESULTS: We report a child with achondroplasia scheduled for decompressive surgery for severe lumbar canal stenosis presenting with neurological claudication and knee weakness. While waiting for surgery during the COVID-19 pandemic, she developed generalized fatigability and severe weakness raising concerns of acute worsening of cord compression. Urgent investigations ruled out spinal cord compression but identified an unexpected concurrent myasthenia gravis with positive antibodies to acetylcholine receptors. The surgical intervention was postponed averting the potential risk of life-threatening anaesthetic complications. She was successfully managed with a combination of pyridostigmine, steroids, azathioprine, and plasma exchange. CONCLUSION: We report the first case of myasthenia gravis in achondroplasia and review implications in the management.