Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “ACHONDROPLASIA”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 91 records · Page 5Linked to original sources
PubMed1995

Mutations of the fibroblast growth factor receptor-3 gene in one familial and six sporadic cases of achondroplasia in Japanese patients.

Achondroplasia, the most common cause of chondrodysplasia in man, is characterized by short-limbed dwarfism, macrocephaly, and dysplasia of metaphyses of the tubular bones. Recently, mutations in the gene encoding fibroblast growth factor receptor-3 (FGFR-3) have been found in patients with achondroplasia. All mutations so far reported had occurred at codon 380, resulting in the substitution of an arginine for a glycine in the transmembrane domain of the predicted protein. We have examined the transmembrane domain of the FGFR-3 gene in seven Japanese patients with achondroplasia. Of the six cases that were sporadic, all carried a mutation in codon 380; the single familial case bore a novel mutation of a G-to-T transition at codon 375, which resulted in substitution of a cysteine for a glycine.

Achondroplasia↗
PubMed2000

The use of gated cine phase contrast and MR venography in achondroplasia.

OBJECTS: Foramen magnum and jugular foramen stenosis, well-known problems in achondroplasia, may result in brain stem compression and venous outflow obstruction, respectively. We studied a series of children with achondroplasia using gated cine phase contrast (PC) CSF flow studies to evaluate CSF dynamics across the foramen magnum and MR venography (MRV) to depict obstructed venous drainage. METHODS: Ten patients (9 months to 11 years, mean 2.85 years) were referred for possible brain stem compression. MRI included routine sequences, cine PC with velocity encoding (VENC) = 5 cm/s, and MRV. Six patients, including the asymptomatic patient, had brain stem compression without tonsillar herniation; two had tonsillar herniation; and two had neither brain stem compression nor tonsillar herniation. Abnormal tonsillar movement was seen only with tonsillar herniation. MRV showed steno-occlusive disease of the internal jugular vein (IJV) in nine patients, sigmoid sinus in four, and absent or hypoplastic transverse sinus in seven. Veno-occlusive disease was not progressive. No patient had massive hydrocephalus, although larger ventricles were associated with more profuse venous collateral formation and more severe degrees of IJV stenosis. Three patients have undergone CSF diversion. CONCLUSIONS: MR imaging may be useful in defining the pathophysiology of brain stem compression and hydrocephalus in achondroplasia.

Achondroplasia↗
PubMed2006

The sagging rope sign in achondroplasia--different from Perthes' disease.

OBJECTIVE: The sagging rope sign is a radio-opaque line, seen on radiographs of the hips, with Perthes' disease. The main purpose of this study was to determine the incidence, cause and importance of this sign in achondroplasia, and to reveal how it differs from in Perthes' disease. DESIGN: Serial radiograms, along with 2-dimensional and 3-dimensional CT images were studied in 42 achondroplastic patients. PATIENTS: Forty-two achondroplastic patients, reported at our institute (for routine outpatient consultation, spine surgeries, deformity corrections, limb-lengthening procedures) were included in this study. There were 26 males and 16 females. RESULTS: The sign was observed bilaterally, in all patients. Evaluation of CT images revealed spherical heads, with presence of circumferential overhang in all hips. This circumferential overhang, seen on 3-D CT scan, corresponded to the sagging rope sign on radiographs. CONCLUSIONS: Presence of the sagging rope sign in bilateral hips is a characteristic feature of achondroplasia. It usually appears before epiphyseal closure. Its cause, incidence, and nature differ from Perthes' disease, and its presence does not carry a bad prognosis in achondroplasia.

Achondroplasia↗
PubMed2006

A case of achondroplasia with severe pulmonary hypertension due to obstructive sleep apnea.

Achondroplasia is the most common skeletal dysplasia in children. Achondroplasic patients have a short cranial face and midface hypoplasia. They often have sleep-related respiratory disturbances that lead to hypoxemia caused by midfacial hypoplasia, a small upper airway, hypotonia of airway muscles, or brain stem compression. It has been well described that obstructive sleep apnea can cause pulmonary hypertension (PH) through the mechanism of chronic hypoxemia. However, severe PH due to obstructive-type sleep disorder is rare in patients with achondroplasia. In this report, we describe a 5-year-old girl with achondroplasia whose severe PH was caused by upper-airway obstruction and was resolved gradually after adenotonsillectomy.

Achondroplasia↗
PubMed1999

Abnormal subcortical somatosensory evoked potentials indicate high cervical myelopathy in achondroplasia.

UNLABELLED: Children with achondroplasia may have high cervical myelopathy due to stenosis of the cranio-cervical junction resulting in neurological disability and an increased rate of sudden death. To detect myelopathy we recorded somatosensory evoked potentials (SEPs) after median nerve stimulation in 30 patients with achondroplasia aged 13 months to 18 years (mean 6 years). In addition to the conventional technique of recording the cortical N20 and the central conduction time (CCT), we employed a noncephalic reference electrode recording the subcortical waveforms N13b and P13. generated near the cranio-cervical junction. The findings were related to the clinical status and MRI results. Eighteen patients had MRI evidence of spinal cord compression with indentation or narrowing of the upper cervical cord, and 13 showed signs of myelomalacia. Seven patients had neurological abnormalities. The sensitivities of the SEPs were 0.89 for cervical cord compression, 0.92 for myelomalacia and 1.0 for the clinically symptomatic patients. There were no false-positive results. The subcortical SEPs were more sensitive than the conventional recordings. However, the conventional SEPs were highly specific in the most severely affected patients; here the specificity was 1.0 for patients with myelomalacia and 0.96 for symptomatic patients. Postoperative SEPs improved after occipital decompression in two children. CONCLUSION: The analysis of somatosensory evoked potentials, in particular of subcortical tracings, is useful in the detection of early cervical myelopathy in children with achondroplasia. Early neurosurgical decompression may prevent irreversible damage.

Achondroplasia↗
PubMed1996

Chinese achondroplasia is also defined by recurrent G380R mutations of the fibroblast growth factor receptor-3 gene.

Achondroplasia is the most common form of dwarfism in humans. A recurrent glycine-to-arginine mutation at codon 380 (G380R) of the transmembrane domain of fibroblast growth factor receptor-3 (FGFR-3) was identified in the majority of Western and Japanese patients, which is uncommon in other autosomal dominant genetic diseases. To determine whether this mutation is also common in Chinese patients, we examined the G380R mutation in Chinese patients with achondroplasia. Of ten patients studied, including eight sporadic cases and one family with two affected members, all have the same G380R mutation with a G-to-A transition. Our results support the argument that the G380R mutation of FGFR-3 is the most frequent mutation causing achondroplasia across different populations.

Achondroplasia↗
PubMed2003

Detection of achondroplasia G380R mutation from PCR amplicons by using inosine modified carbon electrodes based on electrochemical DNA chip technology.

The detection of Achondroplasia G380R mutation from real samples was performed by monitoring the oxidation signal of guanine. Inosine-substituted 12-mer capture probes related to the homozygous or heterozygous alleles of Achondroplasia G380R mutation were adsorbed onto carbon paste electrode (CPE) surface. No guanine signal was obtained from the capture probes, since the inosine bases were electroinactive. Then, these probes were hybridized with the denatured PCR samples on the CPE surface. The hybridization between the probe and target sequences was determined by using the oxidation signal of guanine in connection with differential pulse voltammetry (DPV). The oxidation signal of guanine was observed as a result of the specific hybridization between the probe and PCR sample. The changes in the peak height of the guanine signal provided the information whether the PCR sample contained heterozygous allele or homozygous allele. Numerous factors affecting the hybridization and nonspecific binding events were optimized to detect down to 41.24 fmol/ml target DNA. The electrochemical detection of Achondroplasia G380R mutation from PCR samples greatly shortened and simplified the diagnosis for the homozygous mutant type, which is lethal for the newborn.

Achondroplasia↗
PubMed1999

Obstructive sleep apnea in children with achondroplasia: surgical and anesthetic considerations.

OBJECTIVE: To evaluate the prevalence of obstructive sleep apnea in a large population of children with achondroplasia and to evaluate the effectiveness of adenoidectomy and/or tonsillectomy as treatment. METHODS: Retrospective review of 95 children with achondroplasia. RESULTS: Thirty-six patients (38%) had clinical evidence of obstructive sleep apnea. Thirty-four patients underwent surgery, with more than 1 procedure required in 10 children (29%). Adenotonsillectomy was the initial procedure for 22 of 34 patients, and further therapy was required in only 18% of this group. Adenoidectomy was the initial procedure for 10 of 34, with 90% requiring further surgery for recurrent obstructive sleep apnea. Tonsillectomy alone was performed in 2 patients: 1 was effectively treated and 1 later required adenoidectomy. Endotracheal intubation was accomplished in all patients without complication; 53% required a smaller endotracheal tube than would be predicted by their age. Eight postoperative complications were recorded. CONCLUSIONS: Obstructive sleep apnea is very common in children with achondroplasia. Surgery is effective, but recurrent symptoms are common, particularly when the initial procedure is adenoidectomy. The complication rate is higher than that observed in a general pediatric population but is readily managed with standard therapy. Anesthesia can be given safely to these patients with special consideration for limited neck extension and appropriate endotracheal tube size.

Achondroplasia↗
PubMed1991

Variation of quantitative and qualitative changes of enchondral ossification in heterozygous achondroplasia.

Whereas the radiologic features of achondroplasia--the most common type of skeletal dysplasia in adults--are clearly defined there is still some debate about the severity and the type of histologic changes. Earlier descriptions reported severe disturbance of enchondral ossification to be typical of achondroplasia: They are, however, misleading by dealing mostly with cases of lethal neonatal dwarfism (e.g. thanatophoric dysplasia). Newer findings confirmed that only minor, quantitative lesions are typical of heterozygous achondroplasia. But even in recent years some observers noted more severe changes of enchondral ossification. An extensive histologic skeletal survey in a newborn achondroplastic male revealed remarkable findings: It clearly showed that in addition to a generalized, but moderate narrowing of the zones of enchondral ossification focal severe changes were present in various epiphyseal plates including clusterlike arrangement of enlarged chondrocytes, vacuolization, premature calcification and important fibrosis of cartilagineous matrix with membranous ossification. Our findings thus enable us to reconcile the seemingly divergent statements made before.

Achondroplasia↗
PubMed1983

Presumed homozygous achondroplasia. A review and report of a further case.

Presumptive homozygous achondroplasia (PHA) is a rare disorder. The clinical and detailed histological findings of the fifth case of this chondrodystrophy, studied in detail, are presented here. There is a severe disorder of the normal growth of the long bones, whose nature, however, is not well understood; it shows some resemblance to the pathological changes described in thanatophoric dysplasia which also presents many clinical similarities. The aspect of greatest interest, however, is the relation of PHA to the "classical" form of achondroplasia. Some investigators have maintained that in that disorder there are no significant qualitative, and at most some quantitative, alterations in the growth plate to be demonstrated by histologic examination, but have not explained the apparent abnormalities in the development of the bones and in the external phenotype, which appears to be a milder expression of that seen in PHA. In view of the genetic relationship and external phenotypic similarity one would also have expected in "classical" achondroplasia a milder form of the severe changes seen in PHA. Judging by some of the published reports this is not the case. Attention is drawn to this intriguing discrepancy.

Achondroplasia↗
PubMed2003

Overexpression of CNP in chondrocytes rescues achondroplasia through a MAPK-dependent pathway.

Achondroplasia is the most common genetic form of human dwarfism, for which there is presently no effective therapy. C-type natriuretic peptide (CNP) is a newly identified molecule that regulates endochondral bone growth through GC-B, a subtype of particulate guanylyl cyclase. Here we show that targeted overexpression of CNP in chondrocytes counteracts dwarfism in a mouse model of achondroplasia with activated fibroblast growth factor receptor 3 (FGFR-3) in the cartilage. CNP prevented the shortening of achondroplastic bones by correcting the decreased extracellular matrix synthesis in the growth plate through inhibition of the MAPK pathway of FGF signaling. CNP had no effect on the STAT-1 pathway of FGF signaling that mediates the decreased proliferation and the delayed differentiation of achondroplastic chondrocytes. These results demonstrate that activation of the CNP-GC-B system in endochondral bone formation constitutes a new therapeutic strategy for human achondroplasia.

Achondroplasia↗
PubMed2001

Skeletal development of achondroplasia: analysis of genotyped patients.

BACKGROUND: Achondroplasia is a skeletal dysplasia caused by substitution of arginine for glycine at codon 380 (G380R) mutation of the fibroblast growth factor receptor 3. To date, the developmental course of the phenotype (short stature and skeletal characteristics) has not been clarified in the genotyped population. METHODS: The relationship between age and clinical data (height, arm span and measurements of skeletal radiographs) were statistically analyzed from 27 achondroplasia patients with the G380R genotype. RESULTS: The height standard deviation score had positive correlation and decreased with age, while span-to-height ratio did not. Among measurements of skeletal radiographs, the pelvic index, which represents the squared pelvis deformity, were correlated and increased with age. However, interpedicular distance of the first and fourth lumbar vertebrae (L1:L4) ratio as an index for the caudally narrowed pattern of the lumbar spinal canal and fibula-to-tibia ratio for the disproportionally long fibulae were not correlated and did not increase with age. CONCLUSION: In making a clinical diagnosis of achondroplasia in early infancy, it should be noted that short stature and squared pelvis deformity are not prominent.

Achondroplasia↗
PubMedDate not supplied

[Cervical myelopathy in a newborn with achondroplasia].

BACKGROUND: Patients with achondroplasia have an increased risk of apnoea due to cervical myelopathy. The indication for operative decompression can not be made by MRI alone, because signal alteration and osseous compression of the cervico-medullary region without functional relevance are frequent in this disease. CASE REPORT: We report on a male new-born with achondroplasia who displayed apnoeas from the first day of life. Two times, mask ventilation had to be performed. After exclusion of other diseases potentially causing apnoeas, an MRI of the skull and cervical spine revealed cervico-medullary compression due to foramen magnum stenosis, but no signal alterations of brain stem and cervical mark. Recording of somato-sensory evoked potentials (SSEP) of the median nerve showed normal potentials at Erb's point. By contrast, cortical potentials were distinctly abnormal during left-sided stimulation and could not be recorded during right-sided stimulation. Based on these findings, operative decompression of the craniocervical region was performed which led immediately to complete remission of clinical symptoms. At follow-up, MRI revealed a normal width of the foramen magnum and SSEP were markedly improved. CONCLUSION: In newborns with Achondroplasia, SSEP can confirm the functional relevance of osseous compression of the cervico-medullary region, and facilitate the decision for operative decompression.

Achondroplasia↗
PubMed1999

A mouse model for achondroplasia produced by targeting fibroblast growth factor receptor 3.

Achondroplasia, the most common form of dwarfism in man, is a dominant genetic disorder caused by a point mutation (G380R) in the transmembrane region of fibroblast growth factor receptor 3 (FGFR3). We used gene targeting to introduce the human achondroplasia mutation into the murine FGFR3 gene. Heterozygotes for this point mutation that carried the neo cassette were normal whereas neo+ homozygotes had a phenotype similar to FGFR3-deficient mice, exhibiting bone overgrowth. This was because of interference with mRNA processing in the presence of the neo cassette. Removal of the neo selection marker by Cre/loxP recombination yielded a dominant dwarf phenotype. These mice are distinguished by their small size, shortened craniofacial area, hypoplasia of the midface with protruding incisors, distorted brain case with anteriorly shifted foramen magnum, kyphosis, and narrowed and distorted growth plates in the long bones, vertebrae, and ribs. These experiments demonstrate that achondroplasia results from a gain-of-FGFR3-function leading to inhibition of chondrocyte proliferation. These achondroplastic dwarf mice represent a reliable and useful model for developing drugs for potential treatment of the human disease.

Achondroplasia↗
PubMed1997

Biophysical bases for delayed and aberrant motor development in young children with achondroplasia.

Achondroplasia, the most common skeletal dysplasia, is characterized by delayed and aberrant motoric development in childhood. Delays and aberrancy are secondary to the anatomical differences inherent in people with achondroplasia. We present a photographic essay documenting biophysical differences, aberrant pre-orthograde movement strategies, and selected adaptive techniques. A parental questionnaire assessed the presence of, predominance, and ages at which various types of pre-orthograde locomotion were observed. Fine and gross motor skills were assessed contemporaneously by use of the Denver Developmental Screening Test in 93 children with achondroplasia and were found to be more delayed than previously reported. Physicians, therapists, early-childhood educators, and parents should recognize that aberrant does not mean maladaptive and that different development is not defective development.

Achondroplasia↗
PubMed2000

Perioperative intracranial hemorrhage in achondroplasia: a case report.

We report a case of a 35-year-old man with achondroplasia who previously had thoracolumbar decompressive laminectomies, who developed recurrence of spinal stenosis at the thoracolumbar junction. The patient underwent standard repeat thoracolumbar decompression, removal of a disc, and spinal fusion with instrumentation in the prone position. Postoperatively the patient was confused. Computed tomography (CT) revealed hemorrhages in both cerebellar hemispheres with surrounding edema and mild mass effect. These were interpreted as venous hemorrhages. Conservative therapy was successful. This is the first case report of perioperative venous intracranial hemorrhage in the context of spinal surgery for achondroplasia. Distinctive anatomic characteristics of achondroplasia, combined with several potentially modifiable aspects of his management, may have predisposed the patient to this complication.

Achondroplasia↗
PubMed2007

Thoracic and lumbar pedicle morphometry in achondroplasia.

For safe pedicle screw insertion, knowing pedicle anatomy is essential. Pedicle morphometry in achondroplasia has not been quantitatively described. Therefore, we analyzed 302 thoracic and lumbar pedicles in 11 patients using computed tomography. Transverse endosteal diameter, screw path length, transverse angle, sagittal diameter, and sagittal angle were calculated. We analyzed for safe screw length, size, and trajectory. The data were compared with that on healthy people of different races. In patients with achondroplasia, the maximum endosteal diameter was at L5 and the minimum was at T5. Screw path length was longest at L2 and shortest at T2. Most dimensions were smaller compared with those of healthy people. Abnormal anteromedial transverse angulations were observed between T11 to L2. The maximum transverse angulations were at T2. Sagittal diameter was largest at T12 and smallest at T5. The maximum sagittal angle was seen at T2, and at L5 it was caudal. At all levels except L5, the transverse diameter is the limiting factor for screw size. Six-millimeter screws can be used at L5. Screws that are 35 mm or less are safe to use between T7 to L5. There are surgically important differences in the different angles and diameters of thoracic and lumbar pedicles of patients with achondroplasia and those of healthy people.

Achondroplasia↗
PubMedDate not supplied

Genu varum in achondroplasia.

The etiology of genu varum in achondroplasia is the subject of much speculation. The purpose of the current study was to investigate the association between fibular overgrowth and genu varum in achondroplasia. A retrospective analysis was performed on the long-leg radiographs of 48 pediatric patients with achondroplasia. All patients were skeletally immature, and the average age was 7.7 years (range, 3-16 years). Boys were significantly more likely to have varus mechanical tibiofemoral angles than girls (Fisher exact test, P=0.038 for the right leg and P=0.008 for the left leg). The distance from the proximal and distal fibula to the proximal tibia knee and ankle joint orientation lines, respectively, was not associated with the alignment of the lower extremity. We conclude that fibular overgrowth does not correlate with the severity of genu varum.

Achondroplasia↗