Clinical features and FGFR3 mutations of children with achondroplasia / 中国当代儿科杂志

OBJECTIVES@#To study the clinical features and fibroblast growth factor receptor 3 (FGFR3) gene mutations of children with achondroplasia (ACH) through an analysis of 17 cases.@*METHODS@#A retrospective analysis was performed on the clinical data and FGFR3 gene detection results of 17 children with ACH who were diagnosed from January 2009 to October 2021.@*RESULTS@#Of the 17 children with ACH, common clinical manifestations included disproportionate short stature (100%, 17/17), macrocephaly (100%, 17/17), trident hand (82%, 14/17), and genu varum (88%, 15/17). The common imaging findings were rhizomelic shortening of the long bones (100%, 17/17) and narrowing of the lumbar intervertebral space (88%, 15/17). Major complications included skeletal dysplasia (100%, 17/17), middle ear dysfunction (82%, 14/17), motor/language developmental delay (88%, 15/17), chronic pain (59%, 10/17), sleep apnea (53%, 9/17), obesity (41%, 7/17), foramen magnum stenosis (35%, 6/17), and hydrocephalus (24%, 4/17). All 17 children (100%) had FGFR3 mutations, among whom 13 had c.1138G>A hotspot mutations of the FGFR3 gene, 2 had c.1138G>C mutations of the FGFR3 gene, and 2 had unreported mutations, with c.1252C>T mutations of the FGFR3 gene in one child and c.445+2_445+5delTAGG mutations of the FGFR3 gene in the other child.@*CONCLUSIONS@#This study identifies the unreported mutation sites of the FGFR3 gene, which extends the gene mutation spectrum of ACH. ACH is a progressive disease requiring lifelong management through multidisciplinary collaboration.

Natural history of 39 patients with Achondroplasia

OBJECTIVES: To characterize the natural history of 39 achondroplastic patients diagnosed by clinical, radiological and molecular assessments. METHODS: Observational and retrospective study of 39 patients who were attended at a public tertiary level hospital between 1995 and 2016. RESULTS: Diagnosis was made prenatally in 11 patients, at birth in 9 patients and within the first year of life in 13 patients. The most prevalent clinical findings were short stature, high forehead, trident hands, genu varum and macrocephaly. The most prevalent radiographic findings were rhizomelic shortening of the long bones and narrowing of the interpediculate distance of the caudal spine. There was motor developmental delay in 18 patients and speech delay in 16 patients. The most common clinical intercurrences were middle ear dysfunction, sleep apnea, limb pain and obesity from 2 to 9 years of age. One patient was large for the gestational age but did not develop obesity. One patient developed hydrocephalus at 10 years old. The current age of the patients varies from 15 months to 36 years. The molecular study performed by Sanger sequencing of the common heterozygous mutation 1138G>A in FGFR3 was positive in all patients. Four cases were inherited, and 35 were sporadic (paternal age from 19 to 66 years). CONCLUSIONS: The diagnoses were made early based on clinical and radiographic findings. All cases were confirmed molecularly. Despite presenting a benign course, it is necessary to establish a systematic protocol for the surveillance of these patients due to the common clinical intercurrences.

Achondrogenesis: A Lethal Chondrodystrophy.

Achondrogenesis is a type of skeletal dysplasia. Skeletal dysplasias are the heterogeneous class of bone growth disorders resulting in abnormal shape and size of the skeleton. Here, we present a rare case of achondrogenesis which was delivered by induced abortion at 6½ months of gestation. The physical, radiological, and ultrasonographic examinations done raised the possibility of this very rare anomaly. Achondrogensis is characterized by extreme micromelia and marked discrepancy between the relatively large head and the decreased trunk length. This rare condition has got genetic mutations associated with it. Achondrogenesis resembles other chondrodystrophies, therefore, its diagnosis needs to be made promptly and accurately.

Mutation analysis in Indian children with achondroplasia - utility of molecular diagnosis.

OBJECTIVE: Mutation analysis in Indian children with achondroplasia. METHODS: We studied 11 sporadic cases of achondroplasia. Mutation analysis was done by PCR/RFLP (Polymerase chain reaction/Restriction fragment length polymorphism) method. RESULTS: Nine of the 11 cases had mutation G-->A at 1138 nucleotide position in transmembrane domain of fibroblast growth-factor receptor 3 (FGFR3) gene. Substitution G-->A is a common recurrent mutation reported worldwide. In two cases we could not detect any common mutation and also in entire region of transmembrane domain sequenced. There is possibility of mutation in the other regions of FGFR3 gene in these two cases. CONCLUSION: Further study of these two cases is needed in order to define other genotypes resulting in achondroplasia. Postnatal diagnosis of achondroplasia depends on clinical and radiological features. Mutation detection is mainly useful for prenatal diagnosis.

Mutaciones del gen del receptor 3 del factor de crecimiento de fibroblasto (FGFR3) en pacientes chilenos con talla baja idiopática, hipocondroplasia y acondroplasia / Mutations in the fibroblast growth factor receptor 3 gene (FGFR3) in chilean patients with idiopathic short stature, hypochondroplasia and achondroplasia

Background: Achondroplasia and hypochondroplasia are skeletal dysplasias of autosomal dominant inheritance that represent different degrees of severity of the same pathological entity. Both dysplasias are caused by mutations in the Fibroblast Growth Factor Receptor 3 (FGFR3) gene. In achondroplasia more than 95% of the cases studied to date carry the same mutation (G380R). Hypochondroplasia represents a greater clinical and genetic heterogeneity, possibly being confused with "idiopathic short stature". The N540K mutation has been detected in 50-70% of cases of hypochondroplasia and mutations at the 650 locus in approximately 2.8%. Aim: To assess the frequency of N540K and G380R mutations, and changes at the 650 locus in Chilean patients with idiopathic disproportionate short stature, hypochondroplasia and achondroplasia. Patients and Methods: We studied 21 patients referred for idiopathic short stature, 5 with clinically suspected hypochondroplasia and 4 with achondroplasia. The G1138A, G1138C (G380R), and C1620, C1620A (N540K) mutations and the nucleotide changes at the 650 locus were studied using PCR and restriction analysis of genomic DNA. Results: Three out of five hypochondroplasia patients were heterozygous for the N540K mutation. All of the 4 patients with achondroplasia presented the G1138A mutation. None of these mutations were found in patients with idiopathic short stature. Conclusion: Chilean patients with hypochondroplasia and achondroplasia have the same mutations described in other ethnic groups. The identification of mutations in 3 out of 5 patients with hypochondroplasia shows that this analysis is a useful tool for its diagnostic confirmation. In short stature the molecular study should only be indicated in those cases presenting other clinical and/or radiological features of hypochondroplasia (Rev Méd Chile 2003; 131: 1405-10).

Clinical and molecular characteristics of Thai patients with achondroplasia.

Achondroplasia is an autosomal dominant disorder characterized by disproportionately short stature, frontal bossing, rhizomelia, and trident hands. Most patients appear sporadically resulting from a de novo mutation associated with advanced paternal age. A glycine to arginine mutation at codon 380 (G380R) of the fibroblast growth factor receptor 3 gene (FGFR3) was found to be the most common cause of achondroplasia in various populations. We identified and clinically characterized 3 Thai patients with achondroplasia. In all of them, we also successfully identified the G380R mutation supporting the observation that this is the most common mutation in achondroplasia across different ethnic groups including Thai.

Acondrodiplasia: diagnóstico y manejo perinatal: a propósito de un caso / Achondrodisplasia: diagnosis and perinatal management: a purpose of a case

Presentamos un caso de acondrodisplasia heterocigota diagnosticado por ultrasonido. Hacemos énfasis en sus características clínicas, histopatológicas y radiológicas. Se hacen recomendaciones para el diagnóstico y el manejo perinatal

Estudo genética-clínico da hipocondroplasia / Clinico-genetic study of hypochondroplasia

Estudo genético-clínico da hipocondroplasia ressaltando, a partir da investigaçäo de quatro genealogias, a transmissäo autossômica dominante com penetrância completa. Os aspectos clínico-radiológicos säo caracterizados por nanismo micromélico rizomélico com segmento cefálico normal. Os sinais clínicos säo menos acentuados do que aqueles encontrados na acondroplasia. Trata-se de uma entidade rara e pouco conhecida