A 22-month-old male diagnosed with achondroplasia was referred for difficulty in sleeping and was diagnosed to have severe obstructive sleep apnea (OSA) on polysomnography (PSG) (AHI 50.1). This patient had macrocephaly, midface hypoplasia, flat nasal bridge, relative macroglossia and enlarged palatine and adenoid tonsils. The patient underwent bilateral tonsillectomy with adenoidectomy without complication. Six months post-op, repeat polysomnography revealed a still severe (AHI 15.7) OSA with preferential recovery of REM and N3 sleep. Further outpatient follow-up and management is warranted. OSA despite being common in this subset of patients remains overlooked and not prioritized because of the multitude of coexisting concerns. Management of OSA in children with achondroplasia shows improved sleep structure and is helpful for further growth and development.
achondroplasia ; OSA ; tonsillectomy

Humans ; Achondroplasia/therapy*

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.
Achondroplasia/genetics* ; Child ; Humans ; Mutation ; Osteochondrodysplasias/genetics* ; Receptor, Fibroblast Growth Factor, Type 3/genetics* ; Retrospective Studies

Achondroplasia/therapy* ; Consensus ; Female ; Humans ; Pregnancy ; Prenatal Diagnosis

BACKGROUND: Results of limb lengthening in patients with achondroplasia were previously reported in many studies. However, the reports of comparison among the three long bones (femur, tibia, and humerus) are rare, especially for the results of crossed lengthening (lengthening of one femur and contralateral tibia followed by that of the opposite side) for the lower limbs. The purpose of this study was to report the surgical results of a series of limb lengthening in achondroplastic or hypochondroplasia patients at our institution. METHODS: Fifteen patients (14 with achondroplasia and 1 with hypochondroplasia) underwent lower limb lengthening of the femur (n = 32) and tibia (n = 28), and 12 of them underwent crossed lengthening. Humeral lengthening was performed in 14 patients (n = 28). The mean age at the first operation was 11.7 years, and the mean follow-up duration was 66.7 months. The healing index, consolidation period index (duration of consolidation period/gained length), and other radiographic indices were analyzed. Limb length discrepancy and hip-knee-ankle alignment in lower limbs, and the occurrence of difficulties were assessed. RESULTS: The average gain in length for the femur, tibia, and humerus was 8.3 cm, 8.5 cm, and 7.4 cm, respectively. The mean healing index was 29.6 days/cm for the femur, 29.0 days/cm for the tibia, and 27.2 days/cm for the humerus. The mean consolidation period index was 14.7 days/cm for the humerus, which was significantly lower than that in the lower limb (17.3 days/cm for the femur and 17.8 days/cm for the tibia). Of the 12 who underwent crossed lengthening, five showed limb length discrepancy ≥ 1.0 cm. Among their 24 lower limbs, three showed valgus alignment ≥ 5° and one showed varus alignment ≥ 5°. Thirty-two pin site infections and three fractures were conservatively managed. Three femoral fractures, eight equinus deformities, and four cases with premature consolidation of the fibula were surgically treated. Obstacle and true complication related to humeral lengthening were not observed. CONCLUSIONS: Humeral lengthening was relatively effective and safe. Careful attention will be needed to avoid the occurrence of limb length discrepancy or malalignment in crossed lengthening.
Achondroplasia ; Equinus Deformity ; Extremities ; Femoral Fractures ; Femur ; Fibula ; Follow-Up Studies ; Humans ; Humerus ; Lower Extremity ; Osteogenesis, Distraction ; Tibia

BACKGROUND: Achondroplasia is one of the most common types of dwarfism and is inherited as an autosomal dominant disease. The patients with achondroplasia suffer from various complications such as craniofacial, central nervous system, spinal, respiratory and cardiac anomalies.CASE DESCRIPTION: We report a case of a 35-year-old man with achondroplasia who visited the emergency room with right hemiplegia and aphasia within 6 hours after onset. An Initial CT angiography showed the total occlusion of a left internal cerebral artery due to the thrombus. We treated the patient with endovascular thrombectomy using “Solumbra technique” with balloon guiding catheter. The procedure was successful and result was completely recanalized with Thrombolysis in Cerebral Infarction (TICI) scale 3 and the weakness also improved from grade II to grade IV.CONCLUSION: Acute ischemic stroke patients with achondroplasia could be treated with mechanical thrombectomy.
Achondroplasia ; Adult ; Angiography ; Aphasia ; Catheters ; Central Nervous System ; Cerebral Arteries ; Cerebral Infarction ; Dwarfism ; Emergency Service, Hospital ; Hemiplegia ; Humans ; Stroke ; Thrombectomy ; Thrombosis

Quality control for genetic analysis has become more important with a drastic increase in testing volume and clinical demands. The molecular diagnostics division of the Korean Association of Quality Assurance for Clinical Laboratory conducted two trials in 2017 on the basis of molecular diagnostics surveys, involving 53 laboratories. The molecular diagnostics surveys included 37 tests: gene rearrangement tests for leukemia (BCR-ABL1, PML-RARA, AML1-ETO, and TEL-AML1), genetic tests for Janus kinase 2, FMS-like tyrosine kinase 3-internal tandem duplication, FMS-like tyrosine kinase 3-tyrosine kinase domain, nucleophosmin, cancer-associated genes (KRAS, EGFR, KIT, and BRAF), hereditary breast and ovarian cancer genes (BRCA1 and BRCA2), Li-Fraumeni syndrome (TP53), Wilson disease (ATP7B), achondroplasia (FGFR3), hearing loss and deafness (GJB2), Avellino (TGFBI), multiple endocrine neoplasia 2 (RET), Huntington disease, spinocerebellar ataxia, spinal and bulbar muscular atrophy, mitochondrial encephalopathy with lactic acidosis and stroke-like episodes, myoclonic epilepsy ragged red fibre, Leber hereditary optic neuropathy, Prader-raderd Angelman syndrome, Duchenne muscular dystrophy, spinal muscular atrophy, fragile X syndrome, apolipoprotein E genotyping, methylenetetrahydrofolate reductase genotyping, and ABO genotyping. Molecular genetic surveys revealed excellent results for most participants. The external quality assessment program for genetic analysis in 2017 proved useful for continuous education and the evaluation of quality improvement.
Achondroplasia ; Acidosis, Lactic ; Angelman Syndrome ; Apolipoproteins ; Brain Diseases ; Breast ; Deafness ; Education ; Epilepsies, Myoclonic ; Fragile X Syndrome ; Gene Rearrangement ; Hearing Loss ; Hepatolenticular Degeneration ; Huntington Disease ; Janus Kinase 2 ; Korea* ; Laboratory Proficiency Testing ; Leukemia ; Li-Fraumeni Syndrome ; Methylenetetrahydrofolate Reductase (NADPH2) ; Molecular Biology ; Multiple Endocrine Neoplasia ; Muscular Atrophy, Spinal ; Muscular Disorders, Atrophic ; Muscular Dystrophy, Duchenne ; Optic Atrophy, Hereditary, Leber ; Ovarian Neoplasms ; Pathology, Molecular* ; Phosphotransferases ; Quality Control ; Quality Improvement ; Spinocerebellar Ataxias ; Vascular Endothelial Growth Factor Receptor-1

Achondroplasia and hypochondroplasia are the two most common forms of short-limb dwarfism. They are autosomal dominant diseases that are characterized by a rhizomelic shortening of the limbs, large head with frontal bossing, hypoplasia of the mid-face, genu varum and trident hands. Mutations in the fibroblast growth factor receptor-3 (FGFR3) gene, which is located on chromosome 4p16.3, have been reported to cause achondroplasia and hypochondroplasia. More than 98% of achondroplasia cases are caused by the G380R mutation (c.1138G>A or c.1138G>C). In contrast, the N540K mutation (c.1620C>A) is detected in 60-65% of hypochondroplasia cases. Tests for common mutations are often unable to detect the mutation in patients with a clinical diagnosis of hypochondroplasia. In this study, we presented a case of familial hypochondroplasia with a rare mutation in FGFR3 identified by next generation sequencing.
Achondroplasia ; Diagnosis* ; Dwarfism ; Extremities ; Fibroblast Growth Factors ; Genu Varum ; Hand ; Head ; High-Throughput Nucleotide Sequencing ; Humans

The Diagnostic Genetics Subcommittee of Korean Association of External Quality Assessment Service conducted two trials in 2015 based on cytogenetics and molecular genetics surveys. A total of 43 laboratories participated in the chromosome surveys, 31 laboratories participated in the fluorescence in situ hybridization surveys, and 133 laboratories participated in the molecular genetics surveys. All except one laboratory showed acceptable results in the cytogenetics surveys. The molecular genetics surveys included the following tests: Mycobacterium tuberculosis detection, hepatitis B and C virus detection and quantification, human papilloma virus genotyping, gene rearrangement tests for leukaemias and lymphomas, genetic tests for JAK2, FMS-like tyrosine kinase 3, nucleophosmin, cancer-associated genes (KRAS, EGFR, KIT, and BRAF), hereditary breast and ovarian cancer genes (BRCA1 and BRCA2), Li-Fraumeni syndrome (TP53), Wilson disease (ATP7B), achondroplasia (FGFR3), hearing loss and deafness (GJB2 ), multiple endocrine neoplasia 2 (RET), Huntington disease, spinocerebellar ataxia, spinal and bulbar muscular atrophy, mitochondrial encephalopathy with lactic acidosis and stroke like episodes, myoclonic epilepsy ragged red fibre, Leber hereditary optic neuropathy, Prader-Willi/Angelman syndrome, Duchenne muscular dystrophy, spinal muscular atrophy, fragile X syndrome (FMR1), apolipoprotein E genotyping, methylenetetrahydrofolate reductase genotyping, ABO genotyping, cytochrome P450 2C9 genotyping, cytochrome P450 2C19 genotyping, and DNA sequencing analysis. The molecular genetics surveys showed excellent results for most of the participants. The external quality assessment program for genetics analysis in 2015 proved to be helpful for continuous education and the evaluation of quality improvement.
Achondroplasia ; Acidosis, Lactic ; Apolipoproteins ; Breast ; Cytochrome P-450 Enzyme System ; Cytogenetics ; Deafness ; Education ; Epilepsies, Myoclonic ; Fluorescence ; fms-Like Tyrosine Kinase 3 ; Fragile X Syndrome ; Gene Rearrangement ; Genetics* ; Hearing Loss ; Hepatitis B ; Hepatolenticular Degeneration ; Humans ; Huntington Disease ; In Situ Hybridization ; Korea* ; Li-Fraumeni Syndrome ; Lymphoma ; Methylenetetrahydrofolate Reductase (NADPH2) ; Molecular Biology ; Multiple Endocrine Neoplasia ; Muscular Atrophy, Spinal ; Muscular Disorders, Atrophic ; Muscular Dystrophy, Duchenne ; Mycobacterium tuberculosis ; Optic Atrophy, Hereditary, Leber ; Ovarian Neoplasms ; Papilloma ; Quality Improvement ; Sequence Analysis, DNA ; Spinocerebellar Ataxias ; Stroke

PURPOSE: Although bilateral lower-limb lengthening has been performed on patients with achondroplasia, the outcomes for the tibia and femur in terms of radiographic parameters, clinical results, and complications have not been compared with each other. We proposed 1) to compare the radiological outcomes of femoral and tibial lengthening and 2) to investigate the differences of complications related to lengthening. MATERIALS AND METHODS: We retrospectively reviewed 28 patients (average age, 14 years 4 months) with achondroplasia who underwent bilateral limb lengthening between 2004 and 2012. All patients first underwent bilateral tibial lengthening, and at 9-48 months (average, 17.8 months) after this procedure, bilateral femoral lengthening was performed. We analyzed the pixel value ratio (PVR) and characteristics of the callus of the lengthened area on serial radiographs. The external fixation index (EFI) and healing index (HI) were computed to compare tibial and femoral lengthening. The complications related to lengthening were assessed. RESULTS: The average gain in length was 8.4 cm for the femur and 9.8 cm for the tibia. The PVR, EFI, and HI of the tibia were significantly better than those of the femur. Fewer complications were found during the lengthening of the tibia than during the lengthening of the femur. CONCLUSION: Tibial lengthening had a significantly lower complication rate and a higher callus formation rate than femoral lengthening. Our findings suggest that bilateral limb lengthening (tibia, followed by femur) remains a reasonable option; however, we should be more cautious when performing femoral lengthening in selected patients.
Achondroplasia/*surgery ; Adolescent ; Bone Lengthening/*methods ; Child ; Child, Preschool ; Female ; Femur/radiography/*surgery ; Humans ; Male ; Retrospective Studies ; Tibia/radiography/*surgery ; Treatment Outcome ; Young Adult