Clinical Practice Guidelines for Achondroplasia*

Abstract

Achondroplasia (ACH) is a skeletal dysplasia that presents with limb shortening, short stature, and characteristic facial configuration. ACH is caused by mutations of the FGFR3 gene, leading to constantly activated FGFR3 and activation of its downstream intracellular signaling pathway. This results in the suppression of chondrocyte differentiation and proliferation, which in turn impairs endochondral ossification and causes short-limb short stature. ACH also causes characteristic clinical symptoms, including foramen magnum narrowing, ventricular enlargement, sleep apnea, upper airway stenosis, otitis media, a narrow thorax, spinal canal stenosis, spinal kyphosis, and deformities of the lower extremities. Although outside Japan, papers on health supervision are available, they are based on reports and questionnaire survey results. Considering the scarcity of high levels of evidence and clinical guidelines for patients with ACH, clinical practical guidelines have been developed to assist both healthcare professionals and patients in making appropriate decisions in specific clinical situations. Eleven clinical questions were established and a systematic literature search was conducted using PubMed/MEDLINE. Evidence-based recommendations were developed, and the guidelines describe the recommendations related to the clinical management of ACH. We anticipate that these clinical practice guidelines for ACH will be useful for healthcare professionals and patients alike.

Decompressive Surgery for Craniovertebral Foramen Magnum Stenosis with Medullary Compression in Paediatric Skeletal Dysplasia Syndromes

“…However, when this cervicomedullary compression is relevant, significant potential complications can arise [25,26]. There is no strong evidence to support the proper management of cervicomedullary compression due to craniovertebral stenosis nor for the optimal time for intervention [17]. The skeletal dysplasia diagnosis is straightforward in AChP, however diagnosing other syndromes which include skeletal dysplasia can be extremely challenging.…”

“…In fact, early decompression stops further neurological damage in the caudal brainstem and upper spinal cord and thus prevents myelopathy and respiratory impairment. Hence, surgical decompression should be performed as early as possible [17]. White K, et al analysed the best practice procedures based on evidence and expert consensus about foramen magnum decompression in patients with AChP in the presence of clinical findings (delayed motor development, hypotonia, asymmetric use of the limbs), physical findings (clonus, motor weakness or spasticity, pathologic reflexes), test findings (disturbed sleep pattern with central events) and imaging findings such as an MRI demonstrating a narrow foramen magnum with indentation of the spinal cord (hyperintensity in T2-weighted sequences) -and determined treatment should be semi-urgent in such situations [7].…”

“…These cases require an early and aggressive treatment to avoid medulla oblongata and high cervical spine cord myelopathy which are linked to a higher risk for sudden death by central respiratory failure [15,16]. Kubota T, et al published a literature review and provided clinical guidelines to assist the decision-making process in several aspects of patients with AChP [17]. According to these guidelines, foramen magnum decompression is recommended for managing neural compression due to foramen magnum stenosis associated with neurological symptoms, abnormal neurological findings, and central respiratory disorders (Recommendation grade 1, evidence level B) [17].…”

“…Kubota T, et al published a literature review and provided clinical guidelines to assist the decision-making process in several aspects of patients with AChP [17]. According to these guidelines, foramen magnum decompression is recommended for managing neural compression due to foramen magnum stenosis associated with neurological symptoms, abnormal neurological findings, and central respiratory disorders (Recommendation grade 1, evidence level B) [17]. hydrocephalus, developmental delay, foramen magnum and/or spinal stenosis, with brainstem, spinal cord and nerve roots compression.…”

Thoracolumbar kyphosis in achondroplasia: literature review

“…Мутация в гене FGFR3 (fibroblast growth factor receptor 3) приводит к нарушению процесса энхондрального окостенения из-за подавления дифференциации хондроцитов, нарушения продуцирования и пролиферации хрящевого матрикса. В патологический процесс вовлекаются все длинные трубчатые кости, позвонки и некоторые кости черепа, что придает больным характерный внешний вид [2]. Диспропорциональность телосложения проявляется в укорочении конечностей, в большей степени проксимальных отделов, при относительно нормальной длине туловища, изменении формы черепа [3].…”