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.

Radiological characteristics of skeletal growth in neonates and infants with achondroplasia.

Achondroplasia (ACH) is the most common form of skeletal dysplasia characterized by a rhizomelic short stature. Radiological skeletal findings in pediatric and adult patients with ACH include short long bones, a relatively longer fibula compared to the tibia, a narrow lumbar interpedicular distance, and a hypoplastic iliac wing. Nonetheless, the characteristics of skeletal growth during the neonatal and infantile periods have scarcely been explored. Therefore, this retrospective study aimed to analyze the radiological skeletal growth during the neonatal and infantile periods in 41 Japanese patients with genetically confirmed ACH. The length of long bones in the upper and lower limbs and the lumbar interpedicular distances at L1 and L4 were measured. These parameters showed significant positive correlations with age. The upper segment-to-lower segment ratio in the lower limbs resembled the data of healthy controls from previous reports. The L1/L4 and fibula/tibia ratios increased with age, suggesting that some representative skeletal phenotypes of ACH were less distinct during the neonatal and infantile periods. In conclusion, for the first time, this study radiologically characterized skeletal growth during the neonatal and infantile periods of patients with genetically confirmed ACH.

Recommendations for neuroradiological examinations in children living with achondroplasia: a European Society of Pediatric Radiology and European Society of Neuroradiology opinion paper.

Children living with achondroplasia are at an increased risk of developing neurological complications, which may be associated with acute and life-altering events. To remediate this risk, the timely acquisition of effective neuroimaging that can help to guide clinical management is essential. We propose imaging protocols and follow-up strategies for evaluating the neuroanatomy of these children and to effectively identify potential neurological complications, including compression at the cervicomedullary junction secondary to foramen magnum stenosis, spinal deformity and spinal canal stenosis. When compiling these recommendations, emphasis has been placed on reducing scan times and avoiding unnecessary radiation exposure. Standardized imaging protocols are important to ensure that clinically useful neuroimaging is performed in children living with achondroplasia and to ensure reproducibility in future clinical trials. The members of the European Society of Pediatric Radiology (ESPR) Neuroradiology Taskforce and European Society of Neuroradiology pediatric subcommittee, together with clinicians and surgeons with specific expertise in achondroplasia, wrote this opinion paper. The research committee of the ESPR also endorsed the final draft. The rationale for these recommendations is based on currently available literature, supplemented by best practice opinion from radiologists and clinicians with subject-specific expertise.

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.

Heterozygous variant in FGFR3 underlying severe phenotypes in the second trimester: a case report.

BACKGROUND: Achondroplasia is a congenital skeletal system malformation caused by missense variant of FGFR3 gene with an incidence of 1 per 20,000-30,000 newborns, which is an autosomal dominant inheritance disease. Despite similar imaging features, the homozygous achondroplasia is absolutely lethal due to thoracic stenosis, whereas heterozygous achondroplasia does not lead to fetal death. CASE PRESENTATION: A fetus with progressive rhizomelic short limbs and overt narrow chest was detected by prenatal ultrasound in the second trimester. Gene sequencing results of amniotic fluid sample indicated a rare missense variant NM_000142.4: c.1123G > T(p.Gly375Cys), leading to a glycine to cysteine substitution. Re-sequencing confirmed that it was a heterozygous variant, and thoracic stenosis was then confirmed in the corpse by radiological examination. CONCLUSIONS: We identified a heterozygous variant of the FGFR3 gene as the rare pathogenic variant of severe achondroplasia in a fetus. Heterozygous variants of p.Gly375Cys may have a severe phenotype similar to homozygote. It's crucial to combine prenatal ultrasound with genetic examination to differentiate heterozygous from homozygous achondroplasia. The p.Gly375Cys variant of FGFR3 gene may serve as a vital target for the diagnosis of severe achondroplasia.

[131I]I-MIBG-negative metastases of a recurrent sporadic paraganglioma in a female with achondroplasia.

Not required for Clinical Vignette.

A 66-Year-Old Woman with Achondroplasia and Quadriparesis with an Ovarian Cyst Erroneously Diagnosed as Urinary Retention by an Automated Bladder Scan.

BACKGROUND Automated bladder scanning has become a principal tool in the assessment and management of chronically debilitated patients residing in skilled nursing facilities, hospices, and acute inpatient settings. To a large extent, the bladder scan, generally performed by nursing staff, has replaced physical examination while addressing the differential diagnoses of anuria or voiding disturbances that require consideration of urinary catheterization. Health care providers can quickly master this easily performed technique, and currently, due to confidence in the bladder scan finding, physical examination with suprapubic palpation and percussion may be carelessly omitted. The case description presented here illustrates how not performing a physical examination can lead to misdiagnosis caused by misinterpretation of bladder scan findings. CASE REPORT A 66-year-old, quadriparetic, chronically ventilated female patient with achondroplasia underwent repeated hospital referrals and bladder catheterizations for presumed flaccid, neurogenic bladder with urinary retention. This postulated diagnosis was based on occasional reports of urinary catheter obstruction as well as on automated bladder scanning indicating a markedly distended bladder. However, the bladder could not be drained by insertion of urinary catheters. Eventually, a proper physical examination excluded the presence of suprapubic fullness compatible with distended bladder and contradicting bladder scan findings, prompting re-examining an overlooked evaluation of computed tomography that reported a huge ovarian cyst. The patient was found to have intact voiding capabilities and is now weaned from the catheter. CONCLUSIONS This case and the literature review underscore drawbacks in automated bladder scanning. This technique should be used as an adjunctive measure rather than a replacement for a physical examination in the evaluation of voiding disturbances, especially when there are discrepancies between bladder scan findings and the volume of urine drained by catheterization.

Radiographic Factors for Progression of Thoracolumbar Kyphosis in Achondroplasia Patients after Walking Age: A Generalized Estimating Equation Analysis.

Background: This study aimed to analyse the trends in changes of radiologic parameters according to age to predict factors affecting the progression of thoracolumbar kyphosis (TLK). Methods: Records of patients with achondroplasia were retrospectively reviewed from July 2001 to December 2020. We measured imaging parameters (T10-L2 angle, sagittal Cobb angle, width, height, and number of wedge vertebrae, and apical vertebral translation [AVT]) of 81 patients with radiographically confirmed TLK. Based on the angle on X-ray taken in 36 months, 49 patients were divided into the progression group (P group, TLK angle ≥ 20°) and resolution group (R group, TLK angle < 20°). The mean values between the groups were compared using Student t-test, and the pattern of changes in each radiologic parameter according to age was analysed using a generalized estimating equation. Results: Some imaging parameters showed significant differences according to age between P group and R group: T10-L2 angle (p < 0.001), sagittal Cobb angle (p < 0.001), AVT (p = 0.025), percentage of wedge vertebral height (WVH) (p = 0.018), and the number of severely deformed wedge vertebral bodies (anterior height less than 30% of posterior) (p = 0.037). Regarding the percentage of wedge vertebral widths (superior and inferior endplates), the difference between the two groups did not significantly increase with age, but regardless of age, it was higher in P group than in R group. Conclusions: The difference in the TLK angle between P group and R group of the achondroplasia patients gradually increased with age. Among the imaging parameters, AVT and WVH could be factors that ultimately affect the exacerbation of kyphosis as the difference between the groups increased significantly over time.

Thoracolumbar stenosis and neurologic symptoms: Quantitative MRI in achondroplasia.

BACKGROUND AND PURPOSE: Whole-spine magnetic resonance imaging (MRI) studies, to identify structural abnormalities associated with the development of symptomatic spinal stenosis in achondroplasia. METHODS: Forty-two subjects with achondroplasia were grouped into four age-related categories. Congenital spinal deformities (vertebral body and disc height, interpedicular distance), acquired spinal degenerative changes, thoracic kyphotic (TK) angle, thoracolumbar kyphotic (TLK) angle, spinal canal widths were evaluated by MRI. RESULTS: Patients in the first three groups were asymptomatic and younger (group 1: 4.4 ± 0.78 years; group 2: 8.18 ± 0.60 years; group 3: 10.95 ± 0.93 years) than the symptomatic group (group 4: 23 ± 1.30 years). Patients showed height of vertebral bodies, whole canal width, and average lumbar interpedicular distance reduced. Discs degeneration was more pronounced in the lumbar region and in symptomatic adult patients. TK and TLK angles showed a positive correlation with age (p < .05, r = .42; p < .05, r = .41), whereas thoracic and thoracolumbar canal width had a negative correlation (p < .05, r = -.69; p < .05, r = -.58). A negative correlation between lumbar discs degeneration and canal width was found only at L1-L3 level (p < .05, r = -.35). At L1-L3, the canal width cutoff value of .59 allowed the differentiation between asymptomatic and symptomatic patients (area under the curve of .966, p < .0001). CONCLUSION: In achondroplasia, the spinal canal narrowing, due to accelerated degenerative changes, is a predisposing factor of symptomatic lumbar spinal stenosis. Lumbar canal MRI is a helpful tool to detect the risk of the development of neurological symptoms; in adult patients, a stenosis higher than 60% of upper lumbar canal could be a critical value for the onset of neurological symptoms.

Improvement of the sagittal alignment of the spine in patients with achondroplasia after subtrochanteric femoral lengthening.

PURPOSE: Limb-lengthening surgery to treat short stature has undergone great development in recent years with the use of intramedullary telescopic nails (TIMNs). A limited number of studies have explored the impact of lower limb lengthening on the spine, though their conclusions are not consistent. The aim of this research is to analyze changes in spinopelvic sagittal alignment and balance after lower limb lengthening in achondroplastic patients. METHODS: Prospective study of patients with achondroplasia treated with bilateral femoral lengthening using an TIMN. Different sagittal spinal and pelvic plane parameters were measured on pre- and 2 year postoperative lateral spine radiographs: cervical lordosis, thoracic kyphosis, TL junction, lumbar lordosis (LL), pelvic incidence, pelvic tilt (PT), sacral slope (SS), and sagittal vertebral axis (SVA). Similarly, information regarding the elongation procedure was recorded. RESULTS: A total of 10 patients were included (60% male), with a median age of 13.39 (2.32) years at first surgery and a median height of 120.3 (5.75) cm. A 10 cm elongation was performed in all patients through femoral subtrochanteric osteotomy. Statistically significant changes were found in LL -15.2 (7.4-17.9)º (p = 0.028), PT 11.7 (10.3-13.4)º (p = 0.018), SS - 11.6 (- 13.4 to - 10.4)º (p = 0.018) and |SVA| - 34.3 (- 39.10 to - 1.7) mm (p = 0.043). CONCLUSION: Bilateral lower limb lengthening in patients with achondroplasia not only increases their size, but also improves sagittal spinopelvic alignment and balance. This may be due to retroversion of the pelvis and subsequent decrease in SS and LL as a result of the increased tightness of the gluteus maximus and hamstring muscles after femoral lengthening through subtrochanteric osteotomy. LEVEL OF EVIDENCE: II, prospective comparative cohort study, before and after intervention.

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.

What Are the Risks and Functional Outcomes Associated With Bilateral Humeral Lengthening Using a Monolateral External Fixator in Patients With Achondroplasia?

BACKGROUND: Many patients with achondroplasia experience functional impairments because of rhizomelic upper extremities (proximal limb shortening). Bilateral humeral lengthening may overcome these functional limitations, but it is associated with several risks, such as radial nerve palsy and insufficient bone regeneration. Only a few studies have reported on patient satisfaction and functional outcome after humeral lengthening in patients with achondroplasia. Furthermore, the reported numbers of adverse events associated with lengthening procedures using external fixators vary widely. QUESTIONS/PURPOSES: (1) Does bilateral humeral lengthening with a monolateral external fixator in patients with achondroplasia reliably improve patient function and autonomy, and what proportion of patients achieved at least 8 cm of humeral lengthening? (2) What adverse events occur after bilateral humeral lengthening with monolateral external fixators? METHODS: Between 2011 and 2019, 44 patients underwent humeral lengthening at our institution. Humeral lengthening was performed in patients with severe shortening of the upper extremities and functional impairments. In humeri in which intramedullary devices were not applicable, lengthening was performed with monolateral external fixators in 40 patients. Eight patients were excluded because they underwent unilateral lengthening for etiologies other than achondroplasia, and another four patients did not fulfill the minimum study follow-up period of 2 years, leaving 28 patients with bilateral humeral lengthening to treat achondroplasia available for analysis in this retrospective study. The patients had a median (interquartile range) age of 8 years (8 to 10), and 50% (14 of 28) were girls. The median follow-up time was 6 years (4 to 8). The median humeral lengthening was 9 cm (9 to 10) with a median elongation of 73% (67% to 78%) from an initial median length of 12 cm (11 to 13). To determine whether this treatment reliably improved patient function and autonomy, surgeons retrospectively evaluated patient charts. An unvalidated retrospective patient-reported outcome measure questionnaire consisting of nine items (with answers of "yes" or "no" or a 5-point Likert scale) was administered to assess the patient's functional improvement in activities of daily living, physical appearance, and overall satisfaction, such that 45 points was the highest possible score. The radiographic outcome was assessed on calibrated radiographs of the humerus. To ascertain the proportion of adverse events, study surgeons performed a chart review and telephone interviews. Major complications were defined as events that resulted in unplanned revision surgery, nerve injury (either temporary or permanent), refracture of the bone regenerate, or permanent functional sequelae. Minor complications were characterized as events that resolved without further surgical interventions. RESULTS: On our unvalidated assessment of patient function and independence, all patients reported improvement at their most recent follow-up compared with scores obtained before treatment (median [IQR] 24 [16 to 28] before surgery versus 44 [42 to 45] at latest follow-up, difference of medians 20 points, p < 0.001). A total of 89% (25 of 28) of patients achieved the desired 8 cm of lengthening in both arms. A total of 50% (14 of 28) of our patients experienced a major complication. Specifically, 39% (11 of 28) had an unplanned reoperation, 39% (11 of 28) had a radial nerve palsy, 18% (5 of 28) had a refracture of the regenerate, and 4% (1 of 28) concluded treatment with a severe limb length discrepancy. In addition, 82% (23 of 28) of our patients experienced minor complications that resolved without further surgery and did not involve radial nerve symptoms. Radial nerve palsy was observed immediately postoperatively in eight of 13 segments, and 1 to 7 days postoperatively in five of 13 segments. The treatment goal was not achieved because of radial nerve palsy in 5% (3 of 56) of lengthened segments, which occurred in 7% (2 of 28) of patients. Full functional recovery of the radial nerve was observed in all patients after a median (IQR) of 3 months (2 to 5). Refractures of bone regenerates were observed in 11% (6 of 56) of humeri in 18% (5 of 28) of patients. Of those refractures, 1 of 6 patients was treated nonsurgically with a hanging cast, while 5 of 6 patients underwent revision surgery with intramedullary rodding. CONCLUSION: Most patients with achondroplasia who underwent humeral lengthening achieved the treatment goal without permanent sequelae; nonetheless, complications of treatment were common, and the road to recovery was long and often complicated, with many patients experiencing problems that were either painful (such as refracture) or bothersome (such as temporary radial nerve palsy). However, using a subjective scale, patients seemed improved after treatment; nevertheless, robust outcomes tools are not available for this condition, and so we must interpret that finding with caution. Considering our discoveries, bilateral humeral lengthening with a monolateral external fixator should only be considered in patients with severe functional impairments because of rhizomelic shortening of the upper extremities. If feasible, internal lengthening devices might be preferable, as these are generally associated with higher patient comfort and decreased complication rates compared with external fixators. LEVEL OF EVIDENCE: Level IV, therapeutic study.

Clinical and radiologic evaluation of a Turkish family with hypochondroplasia and a rare FGFR3 variant.

OBJECTIVES: Hypochondroplasia (HCH) is characterized by disproportionate short stature and regarded as a milder form of achondroplasia (ACH), which is another skeletal dysplasia, both caused by variants in fibroblast growth factor receptor 3 (FGFR3) gene. HCH diagnosis is based on the clinical features and skeletal survey findings. The most common FGFR3 variant in HCH affects the codon 540, leading to substitution of asparagine with lysine in about 70% of patients. CASE PRESENTATION: Herein, we described the clinical and radiographical manifestations of HCH in affected members of a Turkish family with very rare Asn540Thr (c.1619A>C) variant within hot spot of the gene for this condition. CONCLUSIONS: This is a very rarely reported variant in the literature and this report is the first case with this variant in Turkish population. The report also presents the phenotypic variability within a family with the same variant, which is inherent to HCH.

The (extended) achondroplasia foramen magnum score has good observer reliability.

BACKGROUND: Achondroplasia is the most common skeletal dysplasia. A significant complication is foramen magnum stenosis. When severe, compression of the spinal cord may result in sleep apnea, sudden respiratory arrest and death. To avoid complications, surgical decompression of the craniocervical junction is offered in at-risk cases. However, practice varies among centres. To standardize magnetic resonance (MR) reporting, the achondroplasia foramen magnum score was recently developed. The reliability of the score has not been assessed. OBJECTIVE: To assess the interobserver reliability of the achondroplasia foramen magnum score. MATERIALS AND METHODS: Base of skull imaging of children with achondroplasia under the care of Sheffield Children's Hospital was retrospectively and independently reviewed by four observers using the achondroplasia foramen magnum score. Two-way random-effects intraclass coefficient (ICC) was used to assess inter- and intra-observer reliability. RESULTS: Forty-nine eligible cases and five controls were included. Of these, 10 were scored normal, 17 had a median score of 1 (mild narrowing), 11 had a median score of 2 (effacement of cerebral spinal fluid), 10 had a score of 3 (compression of cord) and 6 had a median score of 4 (cord myelopathic change). Interobserver ICC was 0.72 (95% confidence interval = 0.62-0.81). Intra-observer ICC ranged from 0.60 to 0.86. Reasons for reader disagreement included flow void artefact, subtle T2 cord signal and myelopathic T2 cord change disproportionate to canal narrowing. CONCLUSION: The achondroplasia foramen magnum score has good interobserver reliability. Imaging features leading to interobserver disagreement have been identified. Further research is required to prospectively validate the score against clinical outcomes.

Artroplastia de rodilla asistida por ordenador en paciente con acondroplasia: caso clínico / Computer assisted knee arthroplasty in patient with achondroplasia: case report

La acondroplasia es una de las displasias óseas más frecuentes. Los pacientes acondroplásicos presentan grandes deformidades y alteraciones anatómicas en los miembros inferiores, con laxitud ligamentosa y una tasa superior de complicaciones perioperatorias, motivo por el que la cirugía de rodilla en estos pacientes supone un reto para el cirujano ortopédico. El objetivo de este trabajo es exponer los beneficios de la artroplastia de rodilla asistida por ordenador en pacientes con displasia ósea a través de un caso clínico. (AU)

Achondroplasia is one of the most common bones dysplasia’s. Achondroplastic patients present great deformities and anatomical alterations in the lower limbs, with ligamentous laxity and a higher rate of perioperative complications, which is why knee surgery in these patients is a challenge for the orthopaedic surgeon. The aim of this work is to expose the benefits of computer-navegated knee arthroplasty in patients with bone dysplasia through a case report. (AU)

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.

Clinical, Biochemical, Radiological, Genetic and Therapeutic Analysis of Patients with COMP Gene Variants.

Pseudoachondroplasia (PSACH) and multiple epiphyseal dysplasia type 1 (MED1) are two rare skeletal disorders caused by cartilage oligomeric matrix protein (COMP) variants. This study aims to analyze the genotype and phenotype of patients with COMP variants. Clinical information for 14 probands was collected; DNA was extracted from blood for COMP variant detection. Clinical manifestations and radiology scoring systems were established to evaluate the severity of each patient's condition. Serum COMP levels in PSACH patients and healthy subjects were measured. Thirty-nine patients were included, along with 12 PSACH probands and two MED1 probands. Disproportionate short stature, waddling gait, early-onset osteoarthritis and skeletal deformities were the most common features. The height Z-score of PSACH patients correlated negatively with age at evaluation (r = - 0.603, p = 0.01) and the clinical manifestation score (r = - 0.556, p = 0.039). Over 50% of the PSACH patients were overweight/obese. The median serum COMP level in PSACH patients was 16.75 ng/ml, which was significantly lower than that in healthy controls (98.53 ng/ml; p < 0.001). The condition of MED1 patients was better than that of PSACH patients. Four novel variants of COMP were detected: c.874T>C, c.1123_1134del, c.1531G>A, and c.1576G>T. Height Z-scores and serum COMP levels were significantly lower in patients carrying mutations located in calmodulin-like domains 6, 7, and 8. As the two phenotypes overlap to different degrees, PSACH and MED1 are suggested to combine to produce "spondyloepiphyseal dysplasia, COMP type". Clinical manifestations and radiology scoring systems, serum COMP levels and genotype are important for evaluating patient condition severity.