A long-acting C-natriuretic peptide for achondroplasia.

The C-natriuretic peptide (CNP) analog vosoritide has recently been approved for treatment of achondroplasia in children. However, the regimen requires daily subcutaneous injections in pediatric patients over multiple years. The present work sought to develop a long-acting CNP that would provide efficacy equal to or greater than that of vosoritide but require less frequent injections. We used a technology for half-life extension, whereby a drug is attached to tetra-polyethylene glycol hydrogels (tetra-PEG) by ß-eliminative linkers that cleave at predetermined rates. These hydrogels-fabricated as uniform ∼60-µm microspheres-are injected subcutaneously, where they serve as a stationary depot to slowly release the drug into the systemic circulation. We prepared a highly active, stable CNP analog-[Gln6,14]CNP-38-composed of the 38 C-terminal amino acids of human CNP-53 containing Asn to Gln substitutions to preclude degradative deamidation. Two microsphere [Gln6,14]CNP-38 conjugates were prepared, with release rates designed to allow once-weekly and once-monthly administration. After subcutaneous injection of the conjugates in mice, [Gln6,14]CNP-38 was slowly released into the systemic circulation and showed biphasic elimination pharmacokinetics with terminal half-lives of ∼200 and ∼600 h. Both preparations increased growth of mice comparable to or exceeding that produced by daily vosoritide. Simulations of the pharmacokinetics in humans indicated that plasma [Gln6,14]CNP-38 levels should be maintained within a therapeutic window over weekly, biweekly, and likely, monthly dosing intervals. Compared with vosoritide, which requires ∼30 injections per month, microsphere [Gln6,14]CNP-38 conjugates-especially the biweekly and monthly dosing-could provide an alternative that would be well accepted by physicians, patients, and patient caregivers.

Clinical outcomes and medical management of achondroplasia in Japanese children: A retrospective medical record review of clinical data.

Achondroplasia (ACH) is a rare, autosomal dominant skeletal dysplasia characterized by short stature, characteristic facial configuration, and trident hands. Before vosoritide approval in Japan, patients with ACH could start growth hormone (GH) treatment at age 3 years. However, ACH and its treatment in young Japanese children have not been studied. This retrospective, longitudinal, medical records-based cohort study (before vosoritide approval) summarized symptoms, complications, monitoring, surgery/interventions, and height with/without GH in Japanese patients with ACH <5 years. Complications were observed in 89.2% of all 37 patients; 75.7% required surgery or intervention. All patients were monitored by magnetic resonance imaging; 73.0% had foramen magnum stenosis, while 54.1% had Achondroplasia Foramen Magnum Score 3 or 4. Of 28 GH-treated patients, 22 initiating at age 3 years were generally taller after 12 months versus 9 non-GH-treated patients. Mean annual growth velocity significantly increased from age 2 to 3 versus 3 to 4 years in GH-treated patients (4.37 vs. 7.23 cm/year; p = 0.0014), but not in non-GH-treated patients (4.94 vs. 4.20 cm/year). The mean height at age 4 years with/without GH was 83.6/79.8 cm. These results improve our understanding of young patients with ACH in Japan and confirm that early diagnosis of ACH and monitoring of complications help facilitate appropriate interventions.

Review of patients with achondroplasia: a single-center's experience with follow-up and associated morbidities.

Achondroplasia (ACH; MIM #100,800), caused by a heterozygous gain of function pathogenic variant in the fibroblast growth factor receptor 3 gene (FGFR3; MIM*134,934), is the most prevalent and most readily identifiable cause of disproportionate short stature that is compatible with life. In addition, individuals with achondroplasia face significant medical, functional, and psychosocial challenges throughout their lives. This study assessed associated morbidities in patients with achondroplasia at a single center in Turkey. In this study, the clinical findings and associated morbidities of a group of patients with achondroplasia (n = 68) with clinical multidisciplinary follow-up at a single center between the years 2005-2023 are evaluated retrospectively. A total of 68 patients, 30 male (44.1%) and 38 female (55.9%), were evaluated. In the majority (84.2%) of patients, shortness of extremities was detected in the prenatal period at an average of 28.7 gestational weeks (± 3.6 SDS) with the aid of ultrasonography. More than half (n = 34/63, 54%) of the patients had a father of advanced paternal age (≥ 35 years). Among the complications, respiratory system manifestations, including obstructive sleep apnea (70%), ear-nose-throat manifestations including adenoid hypertrophy (56.6%) and otitis media (54.7%), neurological manifestations due to foramen magnum stenosis (53.2%), and skeletal manifestations including scoliosis (28.8%), are represented among the most common. The mortality rate was 7.3% (n = 5/68).Conclusion: This study not only represents the first retrospective analysis of the associated morbidities of patients with achondroplasia from a single center in Turkey but also will provide a reference point for future studies.

Novel therapies for growth disorders.

As we continue to understand more about the complex mechanism of growth, a plethora of novel therapies have recently been developed that aim to address barriers and optimize efficacy. This review aims to explore these novel therapies and provide a succinct review based on the latest clinical studies in order to introduce clinicians to therapies that will soon constitute the future in the field of short stature.  Conclusion: The review focuses on long-acting growth hormone formulations, a novel growth hormone oral secretagogue, novel treatments for children with achondroplasia, and targeted therapies for rare forms of skeletal dysplasias. What is Known: • Recombinant human growth hormone has been the mainstay of treatment for children with short stature for years. • Such therapy is not always effective based on the underlying diagnosis (e.g achondroplasia, Turner syndrome). Compliance with daily injections is challenging and can directly affect efficacy. What is New: • Recent development of long-acting growth hormone regimens and oral secretagogues can overcome some of these barriers, however several limitations need to be taken into consideration. • Newer therapies for achondroplasia, and other rare forms of skeletal dysplasias introduce us to a new era of targeted therapies for children with short stature. Clinicians ought to be aware of pitfalls and caveats before introducing these novel therapies to every day practice.

The clinical management of children with achondroplasia in Italy: results of clinician and parent/caregiver surveys.

PURPOSE: This study aimed to assess the real-world management of achondroplasia in Italy. METHODS: Two online surveys addressed to (1) parents/caregivers of individuals with achondroplasia and (2) Italian clinicians managing individuals with achondroplasia were conducted to assess real-world perspectives on achondroplasia management. Both surveys collected data on either patient or clinician demographics, details on diagnoses and referrals, disease complications, and views/experiences with limb lengthening surgery. RESULTS: In total, 42 parents/caregivers and 19 clinicians (from 18 hospitals) completed the surveys. According to parents/caregivers, achondroplasia diagnosis was most commonly made in the third trimester of gestation (55% of respondents), with a genetic test performed to confirm the diagnosis in all but one case. In contrast, the clinicians indicated that, while achondroplasia was typically suspected during the prenatal period (78%), diagnosis was more frequently confirmed postnatally (72%). Parents/caregivers reported that the greatest impact of achondroplasia-related complications occurred in their children between the ages of 2-5 years. The most significant complications were otitis, sleep apnoea, stenosis of the foramen magnum or pressure on the spinal cord, and hearing difficulties. Lengthening surgery had been presented as a treatment option to 92% of responding parents/caregivers, with 76% of clinicians viewing surgery favourably. Typically, clinicians' reasons for suggesting limb lengthening surgery were to improve patient quality of life, increase patient autonomy and self-acceptance, improve trunk-limb disproportion, short stature and walking, and ensure that all possible treatment options had been presented to the parents/caregivers. CONCLUSION: This survey provides insight into the real-world management of individuals with achondroplasia in Italy.

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.

Evolution of orthopaedic diseases through four thousand three hundred years: from ancient Egypt with virtual examinations of mummies to the twenty-first century.

PURPOSE: This study conducts a comprehensive comparative analysis of bone pathologies between ancient Egypt and today. We aim to elucidate the prevalence, types, and potential aetiological factors influencing skeletal disorders in these two distinct temporal and cultural contexts. METHODS: The research employs a multidisciplinary approach, integrating osteological, paleopathological, and historical data to understand bone pathologies in mummies and the actual world. Applying radiographs and CT scans as noninvasive techniques has shed new light on past diseases such as fractures, dysplasia, osteoarthritis, surgery, and tuberculosis. Virtual inspection has almost replaced classical autopsy and is essential, especially when dealing with museum specimens. RESULTS: Findings indicate no significant disparities in the prevalence and types of bone pathologies through 4300 years of evolution. Moreover, this study sheds light on the impact of sociocultural factors on bone health. Examination of ancient Egypt's burial practices and associated cultural beliefs provides insights into potential behavioral and ritualistic influences on bone pathologies and the prevalence of specific pathologies in the past and present. CONCLUSION: This comparative analysis illuminates the dynamic of bone pathologies, highlighting the interplay of biological, cultural, and environmental factors. By synthesizing archeological and clinical data, this research contributes to a more nuanced understanding of skeletal health's complexities in ancient and modern societies, offering valuable insights for anthropological and clinical disciplines.

A scoping review of nutrition issues and management strategies in individuals with skeletal dysplasia.

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

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.

Evaluation of Volumetric Bone Mineral Density, Bone Microarchitecture, and Bone Strength in Patients with Achondroplasia Caused by FGFR3 c.1138G > A Mutation.

Achondroplasia (ACH) is a skeletal disorder caused by fibroblast growth factor receptor 3 (FGFR3) variants. Volumetric bone mineral density (vBMD), bone microarchitecture, and strength have not been evaluated in these patients previously. This study aims to evaluate vBMD, bone microarchitecture, and strength in ACH patients. Seventeen patients underwent clinical and biochemical evaluations, and genetic testing. High-resolution peripheral quantitative computed tomography was performed in 10 ACH patients and 21 age- and sex-matched healthy subjects. All individuals had the hotspot mutation of c.1138G > A in FGFR3. Linear growth retardation, disproportionate short stature, and genu varum are the most common manifestations. The mean height was 108.82 ± 24.08 cm (Z score: - 5.72 ± 0.96). Total vBMD in the ACH and the control groups was 427.08 ± 49.29 mg HA/cm3 versus 300.35 ± 69.92 mg HA/cm3 (p < 0.001) at the radius and 336.90 ± 79.33 mg HA/cm3 versus 292.20 ± 62.35 mg HA/cm3 (p = 0.098) at the tibia; both at the radius and tibia, vBMD of trabecular bones was significantly lower in the ACH group than in the control group, but vBMD of cortical bones was slightly higher in the ACH group. Trabecular separation and cortical thickness in the ACH group were significantly higher than those in the control group, but trabecular number was significantly decreased in the ACH group. Stiffness and failure load were only better at the radius in the ACH group. ACH patients have higher total and cortical vBMD, lower trabecular vBMD, worse trabecular bone microarchitecture, thicker cortical bone thickness, and better estimated bone strength.

Current and emerging therapies for Achondroplasia: The dawn of precision medicine.

Achondroplasia is a rare disease affecting bone growth and is caused by a missense mutation in the fibroblast growth factor receptor 3 (FGFR3) gene. In the past few years, there were multiple experimental drugs entering into clinical trials for treating achondroplasia including vosoritide, the first precision medicine approved for this indication. This perspective presents the mechanism of action, benefit, and potential mechanistic limitation of the drugs currently being evaluated in clinical trials for achondroplasia. This article also discusses the potential impact of those drugs not only in increasing the growth of individuals living with achondroplasia but also in improving their quality of life.

Djeho, the Egyptian God's dancer with dwarfism from the thirtieth dynasty.

This manuscript presents some artistic and medical considerations about a representation of an individual with apparent dwarfism. He was found in Saqqara by the British Egyptologist James Edward Quibell, in 1910/11. The naked figure of this individual, Djeho, is carved in profile on the lid of his sarcophagus. He has a height of 120 cm and has characteristic clinical features suggesting achondroplasia.

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.

Australian guidelines for the management of children with achondroplasia.

Achondroplasia is the most common form of skeletal dysplasia. In addition to altered growth, children and young people with achondroplasia may experience medical complications, develop and function differently to others and require psychosocial support. International, European and American consensus guidelines have been developed for the management of achondroplasia. The Australian focused guidelines presented here are designed to complement those existing guidelines. They aim to provide core care recommendations for families and clinicians, consolidate key resources for the management of children with achondroplasia, facilitate communication between specialist, local teams and families and support delivery of high-quality care regardless of setting and geographical location. The guidelines include a series of consensus statements, developed using a modified Delphi process. These statements are supported by the best available evidence assessed using the National Health and Medicine Research Council's criteria for Level of Evidence and their Grading of Recommendations Assessment, Development and Evaluation (GRADE). Additionally, age specific guides are presented that focus on the key domains of growth, medical, development, psychosocial and community. The guidelines are intended for use by health professionals and children and young people with achondroplasia and their families living in Australia.

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.

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.

Dental characteristics of patients with four different types of skeletal dysplasias.

OBJECTIVE: Skeletal dysplasia (SD) comprises more than 450 separate disorders. We hypothesized that their dental features would be distinctive and investigated the tooth characteristics of four patients with different SDs. MATERIAL AND METHODS: Four SD patients with molecularly confirmed diagnoses, Pt-1 acromicric dysplasia, Pt-2 hypophosphatasia and hypochondroplasia, Pt-3 cleidocranial dysplasia, and Pt-4 achondroplasia, were recruited. A tooth from each patient was evaluated for mineral density (micro-computerized tomography), surface roughness (surface profilometer), microhardness, mineral contents (energy-dispersive X-ray), and ultrastructure (scanning electron microscopy and histology), and compared with three tooth-type matched controls. RESULTS: Pt-1 and Pt-3 had several unerupted teeth. Pt-2 had an intact-root-exfoliated tooth at 2 years old. The lingual surfaces of the patients' teeth were significantly smoother, while their buccal surfaces were rougher, than controls, except for Pt-1's buccal surface. The patients' teeth exhibited deep grooves around the enamel prisms and rough intertubular dentin. Pt-3 demonstrated a flat dentinoenamel junction and Pt-2 had an enlarged pulp, barely detectable cementum layer, and ill-defined cemento-dentinal junction. Reduced microhardnesses in enamel, dentin, and both layers were observed in Pt-3, Pt-4, and Pt-1, respectively. Pt-1 showed reduced Ca/P ratio in dentin, while both enamel and dentin of Pt-2 and Pt-3 showed reduced Ca/P ratio. CONCLUSION: Each SD has distinctive dental characteristics with changes in surface roughness, ultrastructure, and mineral composition of dental hard tissues. CLINICAL RELEVANCE: In this era of precision dentistry, identifying the specific potential dental problems for each patient with SD would help personalize dental management guidelines.