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PubMed2006

Rotational profile of the lower extremity in achondroplasia: computed tomographic examination of 25 patients.

PURPOSE: To evaluate lower-extremity rotational abnormalities in subjects with achondroplasia using computed tomography (CT) scans. MATERIALS AND METHODS: CT scans were performed in 25 subjects with achondroplasia (13 skeletally immature, mean age 8.7 years; 12 skeletally mature, mean age 17.6 years). In a total of 50 bilateral limbs, CT images were used to measure the angles of acetabular anteversion, femoral anteversion, and tibial external torsion. Measurement was performed by three examiners and then repeated by one examiner. Inter- and intraobserver agreements were analyzed, and results were compared with previously reported normal values. RESULTS: Mean values for skeletally immature and skeletally mature subjects were 13.6+/-7.5 degrees and 21.5+/-6.4 degrees respectively for acetabular anteversion, 27.1+/-20.8 degrees and 30.5+/-20.1 degrees for femoral torsion, and 21.6+/-10.6 degrees and 22.5+/-10.8 degrees for tibial torsion. Intra- and interobserver agreements were good to excellent. Acetabular anteversion and femoral anteversion in skeletally mature subjects were greater than normal values in previous studies. Both skeletally immature and mature subjects with achondroplasia had decreased tibial torsion compared to normal skeletally immature and mature subjects. CONCLUSION: Lower-extremity rotational abnormalities in subjects with achondroplasia include decreased tibial external torsion in both skeletally immature and mature subjects, as well as increased femoral and acetabular anteversion in skeletally mature subjects.

Achondroplasia↗

PubMed2004

Rapid detection of FGFR3 gene mutation in achondroplasia by DHPLC system-coupling heteroduplex and fluorescence-enhanced primer-extension analysis.

Achondroplasia is a common form of human dwarfism with characteristically rhizomelic shortening of extremities and relative macrocephaly. It is transmitted as an autosomally dominant inheritance, and about 80% of affected individuals result from sporadic mutations without positive family histories. Achondroplasia comes from the genetic point mutations in the fibroblastic growth factor receptor 3 gene (FGFR3), which enables abnormal cartilage growth-plate differentiation and insufficient bony development. The most common genetic mutations in this receptor are G to A at position 1138 (G1138A), which result in the substitution of glycine to arginine at codon 380. Based on genetic information, molecular genetic testing can provide an exact diagnosis comparing to radiological and prenatal ultrasound evaluations. Here we introduce denaturing high-performance liquid chromatography (DHPLC) for the detection of 17 cases of achondroplasia and 120 unaffected cases. After coupling heteroduplex and fluorescence-enhanced primer-extension analysis, all affected patients with G1138A were identified successfully. In conclusion, we demonstrated that DHPLC is an efficient, accurate, and sensitive technique to detect the single gene mutation of achondroplasia in clinical applications.

Achondroplasia↗

PubMed1998

Sleep-disordered breathing in children with achondroplasia.

OBJECTIVE: Our objective was to characterize sleep-disordered breathing in 88 children with achondroplasia aged 1 month to 12.6 years. RESULTS: At the time of their initial polysomnography, five children had previously undergone tracheostomy, and seven children required supplemental oxygen. Initial polysomnography demonstrated a median obstructive apnea index of 0 (range, 0 to 19.2 apneas/hr). The median number of central apneas with desaturation per study was 0.5 (0 to 49), the median oxygen saturation nadir was 91% (50% to 99%), and the median peak end-tidal pCO2 was 47 mm Hg (36 to 87 mm Hg). Forty-two children (47.7%) had abnormal initial study results, usually caused by hypoxemia. Two children with severe obstructive sleep apnea eventually required continuous positive airway pressure therapy, and three additional children required tracheostomies. CONCLUSIONS: (1) Children with achondroplasia often have sleep-related respiratory disturbances, primarily hypoxemia. (2) The majority do not have significant obstructive or central apnea; however, a substantial minority are severely affected. (3) Tonsillectomy and adenoidectomy decreases the degree of upper airway obstruction in most but not all children with achondroplasia and obstructive sleep apnea. (4) Restrictive lung disease can present at a young age in children with achondroplasia.

Achondroplasia↗

PubMed2026

Phase 3 Trial of Oral Infigratinib in Children with Achondroplasia.

BACKGROUND: Achondroplasia is a genetic skeletal condition caused by FGFR3 pathogenic variants. Infigratinib, an oral FGFR1-3 tyrosine kinase inhibitor, down-regulates key pathways in the pathogenesis of achondroplasia. METHODS: In this phase 3, multicenter, double-blind, placebo-controlled trial, we randomly assigned children with achondroplasia (3 to 17 years of age) in a 2:1 ratio to receive infigratinib (at a dose of 0.25 mg per kilogram of body weight) or placebo once daily for 52 weeks. The primary end point was the change from baseline in the annualized height velocity in the infigratinib group as compared with the placebo group at week 52. Key secondary end points were the change from baseline in the height z score and in the upper-to-lower body segment ratio at week 52. The primary analysis evaluated the treatment effect at week 52 in the full analysis population, with missing data handled with a prespecified imputation approach. RESULTS: In all, 114 patients underwent randomization: 75 patients to receive infigratinib (with 1 withdrawal before treatment) and 39 patients to receive placebo. The difference between infigratinib and placebo in the least-squares mean change from baseline to week 52 was 1.74 cm per year (95% confidence interval [CI], 1.31 to 2.17; P<0.001) for the annualized height velocity, 0.32 (96% CI, 0.23 to 0.41; P<0.001) for the height z score, and -0.02 (96% CI, -0.06 to 0.01) for the upper-to-lower body segment ratio. Adverse events occurred in 71 of 74 patients (96%) in the infigratinib group and in 37 of 39 patients (95%) in the placebo group; serious adverse events occurred in 4 of 74 patients (5%) and 1 of 39 patients (3%), respectively. No serious adverse events or adverse events leading to treatment discontinuation were considered by the investigator to be related to infigratinib or placebo. CONCLUSIONS: In children with achondroplasia, treatment with once-daily oral infigratinib for 52 weeks resulted in a significantly greater increase from baseline in the annualized height velocity than placebo. (Funded by BridgeBio Pharma; PROPEL 3 ClinicalTrials.gov number, NCT06164951; EudraCT number, 2023-506130-67.).

Adolescent↗

PubMed1996

Limb lengthening in children with achondroplasia. Differences based on gender.

Twelve achondroplastic dwarfs underwent serial limb lengthening during childhood. All had repeated bilateral simultaneous elongation of their lower limbs. The height of these patients was plotted on growth curves for children with achondroplasia. The end results were evaluated after all patients reached skeletal maturity. Growth acceleration was seen in male patients with achondroplasia, but no such effect was seen in females. The female patients lost several centimeters as calculated from their predicted final height based on their preoperative growth curve and the centimeters gained by mechanical distraction. The authors' recommendation is to start limb elongation of male patients with achondroplasia at the age of 8 years or older, but to delay limb lengthening in female patients with achondroplasia until approximately 15 years of age to allow for maximal skeletal growth.

Achondroplasia↗

PubMed2006

Posterior osteotomy and instrumentation for thoracolumbar kyphosis in patients with achondroplasia.

STUDY DESIGN: A retrospective case series of surgically treated achondroplastic patients with severe thoracolumbar kyphosis. OBJECTIVE: To evaluate the outcome of surgical treatment for thoracolumbar kyphosis in patients associated with achondroplasia presenting with paraparesis. SUMMARY OF BACKGROUND DATA: Thoracolumbar kyphosis is one of the frequent skeletal manifestations in patients with achondroplasia. Few papers have been published on the surgical treatment of this condition, especially in skeletally mature patients. METHODS: Four patients with achondroplasia who developed neurologic deficit due to severe thoracolumbar kyphosis and underwent surgical treatment were evaluated (mean age, 32.5 years; mean follow-up, 3.0 years). Posterior osteotomy with segmental instrumentation was performed in all cases. The surgical procedures included pedicle subtraction osteotomy in 2 patients without a hypoplastic apical vertebra and spondylectomy with reconstruction of the anterior column in 2 patients with a hypoplastic apical vertebra. Neurologic outcomes (JOA scores), correction of kyphosis, and operative complications were assessed. RESULTS: All patients had gait disturbance, and 2 patients were unambulatory before surgery. The average preoperative JOA score was 5.8 points, which was improved to 9.3 points at the final follow-up (mean recovery rate, 75%). All patients obtained neurologic improvement and became ambulatory either with or without crutches after surgery. The mean preoperative kyphotic angle was 96.3 degrees (range, 57 degrees -117 degrees ). The postoperative angles averaged 55.3 degrees (range, 30 degrees -110 degrees ), yielding a mean correction rate of 43.6%. Neither loss of correction nor pseudarthrosis has been observed during the follow-up period. Partial nerve root laceration and dural tear resulting in transient postoperative muscle weakness were observed in 2 patients as complications. CONCLUSIONS: Posterior spinal osteotomy with segmental instrumentation is a reasonable surgical option for thoracolumbar kyphosis in patients with achondroplasia. Modification of the surgical procedures depending on the presence or absence of the dysplastic changes of the apical vertebra is necessary to obtain optimal results.

Achondroplasia↗

PubMedDate not supplied

Sagging rope sign in achondroplasia is different from Perthes disease.

The "sagging rope" sign is a radiopaque line seen on radiographs of 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. Serial radiograms, along with two- and three-dimensional CT images were studied in 42 patients with achondroplasia. The sign was observed bilaterally in all patients. Evaluation of CT images revealed spherical heads with the presence of circumferential overhang in all hips. This circumferential overhang seen on three-dimensional CT images corresponded to the sagging rope sign on plain radiographs. The 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 in Perthes disease, and its presence does not carry a negative prognosis in achondroplasia.

Achondroplasia↗

PubMed1999

Molecular defects in achondroplasia and the effects of growth hormone treatment.

Achondroplasia is a common skeletal dysplasia with severe growth retardation. Recently, mutations in the fibroblast growth factor receptor 3 (FGFR3) were identified in patients with achondroplasia. In the present study, 70 of 75 Japanese patients with achondroplasia were found to have a G1138A mutation in FGFR3, and two patients had a G1138C mutation. Growth hormone therapy was given to 145 patients with achondroplasia. Significant dose-dependent effects on skeletal growth were obtained, with no long-term adverse effects.

Achondroplasia↗

PubMed1995

Homozygous achondroplasia: US distinction between homozygous, heterozygous, and unaffected fetuses in the second trimester.

PURPOSE: To determine if and at what gestational age prenatal ultrasonography (US) enables distinction between homozygous, heterozygous, and unaffected fetuses when both parents have heterozygous achondroplasia. MATERIALS AND METHODS: Serial US scans of 15 fetuses at 25% risk of homozygous achondroplasia were reviewed retrospectively. Femoral growth curves were established and compared with published standards to determine the gestational age, calculated according to biparietal diameter (BPD), at which femoral length crossed below the 3rd percentile. The presence and severity of achondroplasia were determined clinically after birth. RESULTS: Femoral length crossed the 3rd percentile at 14.0-16.5 weeks BPD age (mean, 15.6 weeks) in the four homozygous fetuses and at 18.2-26.2 weeks BPD age (mean, 21.5 weeks) in the eight heterozygous fetuses. In the three unaffected fetuses, femoral length did not cross percentiles as gestational age increased. CONCLUSION: Establishment of a femoral growth curve in the second trimester with serial US scans enables prenatal distinction between homozygous, heterozygous, and unaffected fetuses when both parents have heterozygous achondroplasia.

Achondroplasia↗

PubMed1999

Achondroplasia and cervicomedullary compression: prospective evaluation and surgical treatment.

The association between sudden death and cervicomedullary compression in infants with achondroplasia has been well described. Prospective clinical and imaging evaluations have been recommended to identify those infants with achondroplasia who are at risk of dying suddenly from respiratory arrest secondary to unrecognized cervicomedullary compression. Since 1988, we have prospectively evaluated 11 infants (average age 13 weeks) with achondroplasia who were asymptomatic for cervicomedullary compression on initial clinical evaluation. Craniocervical magnetic resonance imaging (MRI) findings included narrowing of the foramen magnum, effacement of the subarachnoid spaces at the cervicomedullary junction, abnormal intrinsic cord signal intensity and mild to moderate ventriculomegaly. Two patients with severe cord compression underwent immediate decompression. Two patients developed opisthotonic posturing within 3 months of evaluation and underwent foramen magnum decompression, including suboccipital craniectomy and atlantal laminectomy. Surgery in all cases revealed forward extension of the squamous portion of the occipital bone, thickened posterior rim of the foramen magnum and a dense fibrotic epidural band. There were no complications from surgery. Seven patients did not require surgery and were followed closely. All 11 patients remain asymptomatic at follow-up (mean 4.6 years; range 16 months to 7.3 years), and no patient has required a diversionary shunt procedure. The results of this prospective study confirm that early clinical and MRI evaluations are necessary to determine whether infants with achondroplasia have cervicomedullary compression. With early recognition, an immediate decompression can be performed safely to avoid serious complications associated with cervicomedullary compression, including sudden death.

Achondroplasia↗

PubMed2024

Dual diagnosis of achondroplasia and mandibulofacial dysostosis with microcephaly.

BACKGROUND: Achondroplasia and mandibulofacial dysostosis with microcephaly (MFDM) are rare monogenic, dominant disorders, caused by gain-of-function fibroblast growth factor receptor 3 (FGFR3) gene variants and loss-of-function elongation factor Tu GTP binding domain-containing 2 (EFTUD2) gene variants, respectively. The coexistence of two distinct Mendelian disorders in a single individual is uncommon and challenges the traditional paradigm of a single genetic disorder explaining a patient's symptoms, opening new avenues for diagnosis and management. CASE PRESENTATION: We present a case of a female patient initially diagnosed with achondroplasia due to a maternally inherited pathogenic FGFR3 variant. She was referred to our genetic department due to her unusually small head circumference and short stature, which were both significantly below the expected range for achondroplasia. Additional features included distinctive facial characteristics, significant speech delay, conductive hearing loss, and epilepsy. Given the complexity of her phenotype, she was recruited to the DDD (Deciphering Developmental Disorders) study and the 100,000 Genomes project for further investigation. Subsequent identification of a complex EFTUD2 intragenic rearrangement confirmed an additional diagnosis of mandibulofacial dysostosis with microcephaly (MFDM). CONCLUSION: This report presents the first case of a dual molecular diagnosis of achondroplasia and mandibulofacial dysostosis with microcephaly in the same patient. This case underscores the complexity of genetic diagnoses and the potential for coexistence of multiple genetic syndromes in a single patient. This case expands our understanding of the molecular basis of dual Mendelian disorders and highlights the importance of considering the possibility of dual molecular diagnoses in patients with phenotypic features that are not fully accounted for by their primary diagnosis.

Humans↗

PubMed1996

Overnight growth hormone secretion in achondroplasia: deconvolution analysis, correlation with sleep state, and changes after treatment of obstructive sleep apnea.

The normal profile for overnight GH secretion in achondroplasia has not been previously studied. Factors that have been shown to influence GH secretion include age, obesity, sleep state, and the presence of obstructive sleep apnea (OSA). We assessed GH levels in a group of subjects with achondroplasia, during overnight polysomnography. Nineteen subjects with achondroplasia were studied at 11.3 y of age (median 6.7, range 1.8-30.9). Levels of GH were measured using time-resolved immunofluorometric assay (DELFIA, Pharmacia Biotech Inc.) and analyzed by a deconvolution method. Five subjects were restudied after treatment for OSA. Secretion rates of GH were greater in slow wave (SWS) and rapid eye movement (REM) sleep than in stage one and two (SI-II = light non-REM) sleep (p < 0.01). Total overnight GH secretion decreased with increasing age (r2 = 0.22 p < 0.04). Neither the frequency of arousals, frequency of sleep state transitions nor the severity of OSA correlated with measures of GH secretion. Levels of IGF-I correlated independently with age, body weight (percent ideal), and GH secretion rate (r2 = 0.76, p < 0.001). In a group of five subjects treated for OSA, improved respiratory distress index and reduced sleep state transitions were not associated with significant changes in GH secretion rate by sleep stage; SWS [from 0.62 +/- 0.28 mIU/L/min to 1.02 +/- 0.25 mIU/L/min (NS)] and SI-II sleep [from 0.26 +/- 0.07 mIU/L/min to 0.60 +/- 0.16 mIU/L/min (NS)]. However, in those five subjects, a GH secretion peak during the first 2 h of SWS was initially absent, appearing only after treatment of OSA (1.09 +/- 0.38 mIU/L/min) compared with (2.40 +/- 0.59 mIU/L/min (p = 0.01). A profile of overnight GH secretion is presented for subjects with achondroplasia.

Achondroplasia↗

PubMed2000

The molecular and genetic basis of fibroblast growth factor receptor 3 disorders: the achondroplasia family of skeletal dysplasias, Muenke craniosynostosis, and Crouzon syndrome with acanthosis nigricans.

Achondroplasia, the most common form of short-limbed dwarfism in humans, occurs between 1 in 15,000 and 40,000 live births. More than 90% of cases are sporadic and there is, on average, an increased paternal age at the time of conception of affected individuals. More then 97% of persons with achondroplasia have a Gly380Arg mutation in the transmembrane domain of the fibroblast growth factor receptor (FGFR) 3 gene. Mutations in the FGFR3 gene also result in hypochondroplasia, the lethal thanatophoric dysplasias, the recently described SADDAN (severe achondroplasia with developmental delay and acanthosis nigricans) dysplasia, and two craniosynostosis disorders: Muenke coronal craniosynostosis and Crouzon syndrome with acanthosis nigricans. Recent evidence suggests that the phenotypic differences may be due to specific alleles with varying degrees of ligand-independent activation, allowing the receptor to be constitutively active. Since the Gly380Arg achondroplasia mutation was recognized, similar observations regarding the conserved nature of FGFR mutations and resulting phenotype have been made regarding other skeletal phenotypes, including hypochondroplasia, thanatophoric dysplasia, and Muenke coronal craniosynostosis. These specific genotype-phenotype correlations in the FGFR disorders seem to be unprecedented in the study of human disease. The explanation for this high degree of mutability at specific bases remains an intriguing question.

Acanthosis Nigricans↗

PubMed2006

Accurate diagnosis of a homozygous G1138A mutation in the fibroblast growth factor receptor 3 gene responsible for achondroplasia.

Achondroplasia is the most common genetic form of dwarfism inherited as an autosomal dominant disorder. Individuals affected with achondroplasia have impaired ability to form bone from cartilage (endochondral bone formation). Homozygous achondroplasia is a neonatal lethal condition. The vast majority of patients with achondroplasia have a G-to-A transition at position 1138 of the fibroblast growth factor receptor 3 (FGFR3) cDNA sequence, resulting in the Gly-to-Arg substitution at position 380 of the FGFR3 protein. This mutation has been diagnosed by SfcI digestion of amplified genomic DNA. However, it has also been demonstrated that the SfcI digestion protocol does not consistently distinguish between DNA samples heterozygous and homozygous for the G1138A substitution. This study was designed to improve the molecular diagnosis based on the polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) techniques for the FGFR3 G1138A mutation. The newly designed forward primer contains one mismatch (G at position 1136) from the FGFR3 cDNA sequence (A at position 1136), thereby creating a PstI site (CTGCAG at positions 1134 to 1139) in the amplified DNA from alleles containing the G1138A mutation. The PCR-RFLP technique based on the PstI digestion of amplified genomic DNA with a novel forward primer shows 100% accuracy in diagnosis of the G1138A mutation in heterozygous and homozygous individuals.

Achondroplasia↗

PubMed1980

Spinal neurological complications of achondroplasia. Results of surgical treatment.

Spinal neurological complications caused the admission of 17 patients with achondroplasia to the UCLA affiliated hospitals between 1955 and 1979. These patients constituted 41% of all achondroplastic patients admitted during that period. The spinal stenotic syndromes could be divided into three groups: Group I: thoracolumbar stenosis (10 patients); Group II: foramen magnum and upper cervical stenosis (five patients); and Group III: generalized spinal stenosis (two patients). Eleven patients underwent a total of 18 decompressive operative procedures for treatment of paraparesis, quadriparesis, sensory deficits, and sphincter dysfunction. Excellent results were obtained with patients in Group I and II, 77% of whom were ambulatory and continent postoperatively. Two patients in Group III fared less well, showing steady neurological deterioration despite multiple operative procedures. The spectrum of spinal neurological manifestations secondary to achondroplasia is reviewed. Problems with conventional radiological studies and the potential role of computerized tomographic analysis of such patients are discussed. Recommendations for surgical technique are made. Early recognition, prompt clinical evaluation, and safe and accurate radiological analysis of spinal neurological complications of achondroplasia will allow appropriate decompressive surgical procedures to be performed. Excellent results may be anticipated in the reversal and prevention of neurological deficit secondary to achondroplasia with such an approach.

Achondroplasia↗

PubMed2006

Cervicomedullary decompression for foramen magnum stenosis in achondroplasia.

OBJECT: Achondroplasia is the most common hereditary form of dwarfism, and is characterized by short stature, macrocephaly, and a myriad of skeletal abnormalities. In the pediatric population, stenosis and compression at the level of the cervicomedullary junction commonly occurs. The goal in this study was to assess the outcomes in children with achondroplasia who underwent cervicomedullary decompression. METHODS: Forty-three pediatric patients with heterozygous achondroplasia and foramen magnum stenosis underwent 45 cervicomedullary decompressions at the authors' institution over an 11-year period. After surgical decompression, complete resolution or partial improvement in the preoperative symptoms was observed in all patients. There were no deaths in the treated patients. The surgical morbidity rate was low and usually consisted of a cerebrospinal fluid (CSF) leak in patients in whom the dura mater had been opened (either intentionally or accidentally). This problem was successfully managed in all cases with local measures (wound oversewing) or CSF diversion. CONCLUSIONS: In this review the authors demonstrate that decompression of the cervicomedullary junction in the setting of achondroplasia may be accomplished safely with significant clinical benefit and minimal morbidity.

Achondroplasia↗

PubMed1999

Compound heterozygosity for the Achondroplasia-hypochondroplasia FGFR3 mutations: prenatal diagnosis and postnatal outcome.

We report on a male newborn infant, a compound carrier of heterozygous mutations in the FGFR3 gene causing achondroplasia and hypochondroplasia. The mother has achondroplasia and carries the common G1138 (G380R) mutation in the FGFR3 gene; the father has hypochondroplasia due to the C1620A (N540K) mutation in the same gene. The fetus was found to carry both mutations diagnosed prenatally by amniocentesis at 17.6 weeks of gestation, following maternal serum screening which showed an increased risk for Down syndrome (1:337). Detailed fetal ultrasound studies showed a large head, short limbs, and a small chest at 22 weeks of gestation. The changes were more severe than those of either achondroplasia or hypochondroplasia. The patient was born by cesarean section at 38 weeks of gestation and had rhizomelic shortness of the upper and lower limbs with excess skin folds, large head, enlarged fontanelles, frontal bossing, lumbar gibbus, trident position of the fingers, and a narrow chest with a horizontal line of demarcation at the narrowest area of the chest. Skeletal radiographs showed shortness of the long bones and flare of metaphyses. He had respiratory difficulties and was treated with nasal prongs. Seizures developed on day 2 of life and recurred on day 9 and responded to treatment with phenobarbital. Brain computed tomographic scan showed possible grey matter heterotopia, partial agenesis of the corpus callosum, and cortical dysplasia. To our knowledge, there are only two previously published cases of compound heterozygous achondroplasia-hypochondroplasia patients. The diagnosis was confirmed by DNA mutation analysis of the FGFR3 gene in both cases.

Abnormalities, Multiple↗

PubMed1999

Bone dysplasia series. Achondroplasia, hypochondroplasia and thanatophoric dysplasia: review and update.

The authors summarize the clinical, genetic and histopathologic features, as well as the complications, and radiological diagnosis of 3 related generalized short-limb skeletal dysplasias: achondroplasia, hypochondroplasia and thanatophoric dysplasia. In all of these dysplasias, there is abnormal endochondral ossification, but periosteal ossification is not affected. These 3 relatively common entities are known to be allelic to the same gene: the fibroblast growth factor receptor 3 gene on chromosome 4p. Heterozygous achondroplasia is the most common nonlethal skeletal dysplasia. The distinctive clinical and radiological features allow a precise diagnosis, as there is little variability in the appearance of affected patients. There is also a very evident molecular homogeneity. On histopathology of the growth plate, there is a quantitative decrease in endochondral ossification. Precise prenatal ultrasonographic diagnosis is possible in the third trimester, and sometimes even in the second. Hypochondroplasia is a relatively common, milder form of achondroplasia, which varies within and between families and lacks the neurological complications often seen in achondroplasia of this group. An accurate prenatal ultrasonographic diagnosis is rare. There are milder changes on histology of the growth plate. Thanatophoric dysplasia is the lethal and most severe dysplasia. It has distinct features--mainly short tubular bones and short ribs with platyspondyly--allowing a precise radiologic and prenatal ultrasonographic diagnosis. On histopathology of the growth plate, there is disruption of endochondral ossification.

Achondroplasia↗