eMedicine Specialties > Pediatrics: Genetics and Metabolic Disease > Genetics

Achondroplasia

Germaine L Defendi, MD, MS, FAAP, Associate Clinical Professor, Department of Pediatrics, Olive View-UCLA Medical Center

Updated: Aug 14, 2009

Introduction

Background

Achondroplasia, a nonlethal form of chondrodysplasia, is the most common form of short-limb dwarfism. It is inherited as a mendelian autosomal dominant trait with complete penetrance. Approximately 80% of cases are due to new or de novo dominant mutations with a mutation rate estimated to be 0.000014 per gamete per generation. Salient phenotypic features include disproportionate short stature, megalencephaly, a prominent forehead (frontal bossing), midface hypoplasia, rhizomelic shortening of the arms and legs, a normal trunk length, prominent lumbar lordosis, genu varum, and a trident hand configuration.

Height for females with achondroplasia (mean/standard deviation [SD]) compared to normal standard curves. The graph is based on information from 214 females. Adapted from Horton WA, Rotter JI, Rimoin DL, et al. Standard growth curves for achondroplasia. J Pediatr. 1978 Sep; 93(3): 435-8.

Height for males with achondroplasia (mean/2 standard deviations [SDs]) compared to normal standard curves. The graph is based on information from 189 males. Adapted from Horton WA, Rotter JI, Rimoin DL, et al: Standard growth curves for achondroplasia. J Pediatr. 1978 Sep; 93(3): 435-8.

Mean growth velocities (solid line) for males (top) and females (bottom) with achondroplasia compared to normal growth velocity curves. Dashed lines indicate third percentile, mean, and 97th percentile. Data are from 26 males and 35 females. Adapted from Horton WA, Rotter JI, Rimoin DL, et al. Standard growth curves for achondroplasia. J Pediatr. 1978 Sep; 93(3): 435-8.

Upper and lower segment lengths for males (top) and (bottom) with achondroplasia (mean/standard deviation [SD]). Data are from 75 males and 95 females. Adapted from Horton WA, Rotter JI, Rimoin DL, et al. Standard growth curves for achondroplasia. J Pediatr. 1978 Sep; 93(3): 435-8.

Head circumference for females with achondroplasia compared to normal curves (dashed lines). Data are from 145 females. Adapted from Horton WA, Rotter JI, Rimoin DL, et al. Standard growth curves for achondroplasia. J Pediatr. 1978 Sep; 93(3): 435-8.

Head circumference for males with achondroplasia compared to normal curves (dashed lines). Data are from 114 females. Adapted from Horton WA, Rotter JI, Rimoin DL, et al. Standard growth curves for achondroplasia. J Pediatr. 1978 Sep; 93(3): 435-8.

Pathophysiology

Achondroplasia is caused by mutations in the fibroblast growth factor receptor-3 (FGFR3) gene. At present, FGFR3 is the only gene known to cause achondroplasia. This gene has been mapped to chromosome 4, band p16.3 (4p16.3). All causal mutations occur at the exact same location within the gene; hence molecular testing by targeted mutational analysis is easily done and interpreted. The mutations (G1138A, G1138C) cause an increased function of the FGFR3 gene, resulting in decreased endochondral ossification, inhibited proliferation of chondrocytes in growth plate cartilage, decreased cellular hypertrophy, and decreased cartilage matrix production.

The nucleotide G1138A and G1138C mutations of FGFR3 account for 99% of the mutations resulting in a specific point mutation, hence an amino acid substitution. About 98% of cases have the G1138A mutation resulting from a G-to-A point change. One percent of cases have a G-to-C point change at nucleotide 1138, causing the G1138C mutation. A rare missense mutation (Lys650Met) in the tyrosine kinase region of FGFR3 causes a disorder termed severe achondroplasia with developmental delay and acanthosis nigricans (SADDAN) . See Differentials.

Frequency

United States

Frequency has not been documented in the United States.

International

Frequency is believed to be 1 case per 15,000-40,000 births worldwide. In 1986, Orioli et al reported on the frequency of all skeletal dysplasias in a study population of 349,470 live births and stillbirths.¹ Based on their study, the prevalence rate for achondroplasia was estimated to be 0.5-1.5 cases per 10,000 births and the mutation rate to be 1.72-5.57 x 10^-5 per gamete per generation.

Mortality/Morbidity

Sudden death within the first year of life is attributed to abnormalities at the craniocervical junction causing spinal cord compression. Central apnea occurs due arterial compression at the cervical level of the foramen magnum. The small foramen magnum present in these patients may also cause a high cervical myelopathy.

The risk of sudden death for infants with achondroplasia is 2-5%. This risk can be minimized with appropriate assessment of the craniocervical junction, which includes a thorough neurological history and examination, neuroimaging (either CT scanning or MRI), and polysomnography. If neurological abnormalities are detected, referral to medical center with neurosurgical consultation services is indicated.

Caregivers should use an infant carrier with a firm back that gives good neck support and to use a rear-facing car seat for travel as long as possible. Use of mechanical swings and carrying slings should be avoided to limit the potential for uncontrolled head movement.

Thoracolumbar kyphosis occurs in most infants with achondroplasia. Severe kyphosis is related to unsupported sitting of the infant before adequate trunk muscle strength has developed. Angular deformities of the extremities, premature degenerative joint disease, and spinal disorders are common clinical features.

Cervical instability is present in a large number of patients. Great care must be taken with manipulation of the neck, as would occur for preparation of intubation in general anesthesia. Uncontrolled neck movements could cause significant neurological compromise with spinal cord compression.

Obesity, when present, aggravates the morbidity related to lumbar stenosis, nonspecific joint problems, and cardiovascular risks. Based on the weight/height (W/H) curves developed by Hunter et al for boys and girls with achondroplasia, the mean W/H curve in children with achondroplasia matches the control curve until the children reach 75 cm in height. Beyond 75 cm, the weight in children with achondroplasia increases disproportionately to height. The Quetelet index or body mass index (BMI=W/H2) can be used to estimate weight excess in children ages 3-6 years; after that, the Rohrer index (RI=W/H3) should be used for children and adolescents ages 6-18 years.

Respiratory disorders are seen frequently, including apnea and abnormalities of gas exchange. Studies report that as many as 75% of children with achondroplasia have a pathologic apnea index (>30 episodes). Brainstem compression may contribute to central apnea whereas obstructive apnea may be due to midface structural abnormalities such as hypoplasia.

Severe upper airway obstruction occurs in less than 5% in children with achondroplasia. Tonsillectomy and adenoidectomy do not help resolve this obstruction very well in children with achondroplasia. Hypotonicity, a narrow trunk with a small thoracic cage and adenotonsillar hypertrophy all contribute to confining the airway and causing upper airway obstruction.

Children with achondroplasia who have respiratory dysfunction and obstructive sleep apnea (OSA) detected by polysomnography have associated cognitive deficits, as evident in children with OSA within the general population. Restrictive pulmonary disease, with or without restrictive airway disease, occurs in less than 5% of children younger than 3 years old. This risk is greater for those who live at higher elevations.

A study of school-aged children with achondroplasia reported CT findings, including kinking of the medulla and neuroanatomic abnormalities consistent with arrested hydrocephalus, including enlarged ventricles and hypoplasia of the corpus callosum. These CT findings are similar to those seen in children with compensated, unshunted hydrocephalus. The hydrocephalus may be due to increased intracranial venous pressure secondary to stenosis of the sigmoid sinus at the level of the narrowed jugular foramina.

Although their overall cognitive scores are within normal, children with achondroplasia may show mild deficits in visual-spatial tasks. This deficit has been identified in children with arrested hydrocephalus.

Motor milestones are usually delayed for the first year of life due to a large cranium and poor overall muscle tone (hypotonia). Language development is normal, if no conductive hearing loss is present.

Race

No documented race predilection is noted.

Sex

Males and females are equally affected.

Clinical

History

Achondroplasia is primarily due to a de novo mutation; however, some parents who are affected are heterozygous for either the G1138A or G1138C mutation. Identifying families members at risk is helpful in addressing medical treatment plans, offering genetic counseling with options for genetic testing, and providing educational materials and emotional support. 

Once the diagnosis of achondroplasia is made, obtain the following history to avoid serious complications:

• A history of pain, ataxia, incontinence, and apnea may be due to cervicomedullary compression. Cord compression can cause respiratory arrest and progressive quadriparesis. Indications for surgery to release the compression include brisk reflexes, a small foramen magnum, and central hypopnea.
• Obtain a careful history for recurrent otitis media to prevent conductive hearing loss which can be the cause of language delays.
• A history of sleep disturbances² and increased head size may indicate neurologic and respiratory complications.

Physical

• Neurologic findings
  • Hypotonia in infancy and early childhood
  • Delayed motor milestones
  • Normal intelligence with possible minor deficit in visual-spatial tasks
• Craniofacial features:
  • Large calvarial bones in contrast to the small cranial base and facial bones 
  • True megalencephaly (large head) with frontal bossing
  • Midface hypoplasia
  • Dental malocclusion and crowding
• Skeletal features:
  • Disproportionate short stature: The average adult male height is 131 ± 5.6 cm; the average adult female height is 124 ± 5.9 cm (approximately 4 ft for both men and women).
  • Normal trunk length that appears long and narrow, small thoracic cage
  • Rhizomelic shortening of the proximal limbs with redundant skin folds
  • Brachydactyly and trident hand configuration: A marked separation between the ring and middle fingers giving the hand a 3-pronged appearance.
  • Thoracolumbar gibbus (lumbar kyphosis) in infancy, which is replaced by an exaggerated lumbar lordosis once ambulation begins
  • Hyperextensibility of most joints, especially the knees.
  • Limited elbow extension and rotation
  • Genu varum (bow legs)
• Radiographic findings
  • Contracted skull base
  • Progressive interpedicular narrowing in the lumbar spine region
  • Short pedicles which can cause spinal stenosis
  • Short femoral neck and metaphyseal flaring
  • Dysplastic ilium, narrow sacroiliac groove, flat-roofed acetabula

Causes

• Advanced paternal age (age >35 y) is identified as a risk factor in de novo cases of achondroplasia, suggesting that factors influencing DNA replication or repair during spermatogenesis may predispose men to the occurrence of G1138 FGFR3 mutations.

Differential Diagnoses

Achondrogenesis
Asphyxiating Thoracic Dystrophy (Jeune Syndrome)
Hypochondroplasia
SADDAN Dysplasia
Skeletal Dysplasia
Thanatophoric Dysplasia

Other Problems to Be Considered

The phenotype and radiographic findings of achondroplasia are distinctive; identification of affected children should not be confusing, however there are other forms of short-limb dwarfism that are associated with the mutations of gene FGFR3. Confirmatory diagnostic testing by genetic molecular studies is available.

• Hypochondroplasia: A chondrodysplasia that occurs less often than achondroplasia.  Hypochondroplasia differs from achondroplasia due to the lack of craniofacial involvement and milder phenotypic changes in the hands and spine. Inheritance is also autosomal dominant and the gene has been mapped to 4p16.3, but with a different mutation change within the same gene.
• SADDAN: This rare genetic disorder is characterized by extremely short stature, profound developmental delay, marked tibial bowing and acanthosis nigricans. These patients do survive beyond the newborn period, unlike those diagnosed with thanatophoric dysplasia (a lethal condition).
• Thanatophoric dysplasia: A form of skeletal dysplasia with significant newborn mortality due to small thoracic cage and pulmonary insufficiency. Patients that survive beyond the neonatal period have profound developmental delay and severe growth deficiency.  Inherited as an autosomal dominant, all cases are due to a de novo mutation.

Workup

Laboratory Studies

• Commercially available direct DNA analysis of FGFR3 mutations identifies the G1138 (G380R) mutation in patients with achondroplasia, and a novel missense mutation (Lys650Met) in tyrosine kinase. Direct DNA analysis of FGFR3 mutations can be used for prenatal screening in families at risk (ie, parents who are heterozygous for either the G1138A or the G1138C mutation).
• Epiphyseal growth plate cartilage findings are histologically, immunohistochemically, biochemically, and electron microscopically normal.

Imaging Studies

Diagnosis is based on typical clinical and radiologic features. Radiologic features confirm the diagnosis of achondroplasia and exclude other conditions.

• Radiography
  • Perform a skeletal survey.
  • Plain radiography performed at birth can identify achondroplasia.
  • Radiographic findings include a contracted skull base, normal trunk length, rhizomelic shortening of the long bones, trident hands, a square-shaped pelvis with small sacrosciatic notch, proximal femoral radiolucency, and shortened vertebral pedicles. In older children, a characteristic chevron-shaped distal femoral epiphyses is seen. Growth plates are also shortened.
  • When disproportionately short limbs are observed on fetal ultrasonography, plain film radiographs of the neonate may help distinguish achondroplasia from other conditions.
• MRI: MRI findings combined with somatosensory-evoked potentials can reveal spinal stenosis in the lumbar spine or foramen magnum.
• Ultrasonography
  • Perform head ultrasonography at birth and at age 2 months, 4 months, and 6 months to monitor ventricular size for hydrocephalus and/or an intracranial bleed. In addition, perform ultrasonography if the fontanelle is unusually large and full, if the occipitofrontal circumference (OFC) increases disproportionately over time, or if symptoms of hydrocephalus develop.
  • Routine fetal ultrasonography is performed during prenatal visits of most pregnancies. Ultrasonography is recommended for prenatal diagnosis if there is concern for achondroplasia.
  • Perform fetal ultrasonography to evaluate skeletal anomalies and to measure the long bones for size, shape, bowing, symmetry, and quality of calcification.
  • Perform serial ultrasonography starting at the second trimester to plot the femoral length growth curves to distinguish individuals with homozygous (lethal) and heterozygous (nonlethal) achondroplasia from unaffected individuals because the characteristic features of heterozygous achondroplasia may not be evident before this time. 
  • Use fetal ultrasonography to evaluate the skull for size and shape.

Treatment

Medical Care

• Closely monitor growth in patients with achondroplasia.
  • Weight, height, and occipitofrontal circumference (OFC) monthly for the first year of life.
  • Measure the upper-to-lower segment ratio.
• Monitor developmental milestones in gross and fine motor, language and social/adaptive.
• Perform careful neurologic examinations.
• Manage frequent middle ear infections and address any concern for hearing loss.
• Orthodontic evaluation for dental malocclusion and crowding.
• Control weight to prevent obesity and associated co-morbidities.
• Therapy using growth hormone (GH) to foster linear growth.
  • The usefulness of GH therapy in patients with achondroplasia needs to be further studied.
  • Effects of GH therapy appear to continue into the second year of treatment. Many practitioners do not recommend this therapy due to the associated effects of increased deposition of abnormal bone and potential to worsen orthopedic issues such as kyphoscoliosis.
• Anti-inflammatory agents, such as nonsteroidal anti-inflammatory drugs (NSAIDs), are useful to alleviate pain and inflammation for patients with degenerative joint disease.
• Transgenic mice with achondroplasia have been developed, which can potentially speed the research and development of drugs and provide animal models for gene therapy trials.

Surgical Care

• Leg-lengthening procedures using distraction osteogenesis have been performed successfully. Successful height increase is reported to be 12-14 inches. Better outcomes are reported with the use of the Orthofix Garches lengthening device along with tenotomy of the Achilles tendon and syndesmosis, which provide the fewest complications with healing indices similar to those of other operative protocols. Another procedure associated with fewer complications in children and adolescents younger than 14 years is tibia, rather than femur, lengthening.
• In children with signs of craniomedullary compression, surgical treatment to release the compression can improve neurologic, cognitive, and respiratory functions. Indications for the possible need for suboccipital decompression include lower limb hyperreflexia or clonus on examination, central hypopnea demonstrated by polysomnography, and foramen magnum measurements lower than the mean.
• Lumbar laminectomy can be performed for spinal stenosis, which is a condition that usually manifests in early adulthood.
• Spinal fusion can be performed for persistent kyphosis that is not improved with bracing and sitting modification.

Consultations

• Immediately refer patients to a neurologist and/or neurosurgeon for reflex asymmetry, extreme hypotonia, early hand preference, or excessive head growth.
• Additional referrals may be needed for an ear, nose, and throat (ENT) specialist, orthopedist, pulmonologist, or physical therapist depending on clinical concerns.
• Refer to geneticists and genetic counselors for prenatal consultations, options for genetic testing and resources for support organizations.
• Offer psychological support and educational tools to patients who are having difficulty living with disproportionate short stature in today's society.

Diet

• Hunter et al recommend that children with achondroplasia remain within 1 standard deviation (SD) of the mean weight/height (W/H) curve for people with achondroplasia.

Medication

All of the medical treatments used in children with achondroplasia, including growth hormone (GH), have produced variable results.

Hormones

Study results have been contradictory regarding usefulness of GH in achondroplasia. One study of 35 children with achondroplasia showed an increase in growth velocity in the first 2 years of treatment and safety of growth hormone use for 5 years.³

Growth hormone, human (Nutropin, Genotropin, Humatrope)

Stimulates growth of linear bone, skeletal muscle, and organs. Also stimulates erythropoietin, which increases RBC mass.

Dosing

Adult

0.1-0.3 mg/d SC initially

Pediatric

GH deficiency: 0.15-0.3 mg/kg/wk SC divided into daily or 6 times/wk injections
Achondroplasia: 0.04 mg/kg/d or 0.1 IU/kg/d SC

Interactions

Glucocorticoids may decrease growth-promoting effects

Contraindications

Documented hypersensitivity; closed epiphyses, actively growing intracranial tumor, any underlying intracranial lesion

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Caution in diabetes; reconstitute with sterile water for injection if administering to newborns; rotate injection sites to avoid lipodystrophy

Follow-up

Further Outpatient Care

The following recommendations for the medical management and follow-up care of patients with achondroplasia were presented at the First International Symposium on Human Achondroplasia held in Rome, Italy in 1986:

• Growth and head circumference measurements plotted on growth curves standardized for achondroplasia
• Thorough neurologic examinations to include clinical assessment as well as CT scan, MRI, somatosensory-evoked potentials, and polysomnography
• Appropriate medical care for recurrent middle ear infections and dental crowding associated with the craniofacial features seen in achondroplasia.

Complications

• Complications include cervicomedullary compression, spinal stenosis, restrictive and obstructive lung disease, otitis media, and tibial bowing. Other possible complications include development of thoracolumbar kyphosis, symptomatic hydrocephalus, or symptomatic upper cord compression.

Prognosis

• Most individuals with achondroplasia have normal intelligence, lead independent and productive lives and have a normal life expectancy.

Patient Education

• Genetic counseling: Discuss the genetics of cause, recurrence risk, and prenatal diagnosis with families.
• Support groups may help in the following ways:
  • Provide practical information regarding solutions to problems in daily living, such as clothing and furniture resources
  • Provide emotional and psychosocial support for patients and their caregivers living with achondroplasia in today's society.
  • The following are excellent resources to give families assistance:
    • Little People of America, Inc
      Phone: 1-888-LPA-2001 (1-888-572-2001)
      Web site: www.lpaonline.org
    • March of Dimes (MOD)
      Phone: 1-914-997-4488
      Web site: www.marchofdimes.com
    • Human Growth Foundation (HGF)
      Phone: 1-800-451-6434
      Web site: www.hgfound.org
    • Coalition for Heritable Disorders of Connective Tissue
      Phone: 1-888-LPA-2001 (thru Little People of America)
      Web site: www.chdct.org
    • International Skeletal Dysplasia Registry
      Phone: 1-800-CEDARS-1 (1-800-233-2771)
      Web site: www.csmc.edu 
• The following information is adapted from "Health Supervision for Children with Achondroplasia" by the American Academy of Pediatrics Committee on Genetics, published in September 2005:⁴
  • Prenatal visits - Geneticists, obstetricians, and/or pediatricians to educate parents regarding the disorder, inheritance, and prognosis for offspring
  • Infants
    • Review the personal support available to the family.
    • Review contact with support groups.
    • Review the increased risk of serous otitis media due to short eustachian tubes. Indicate that an ear examination is needed with any upper respiratory tract infection.
    • Avoid infant carriers that place the infant in a curled-up position. This does not apply to car safety seats, which should always be used during automobile travel.
  • Early childhood (1-5 y)
    • Discuss adapting the home so the child can become independent (lower the light switches and faucets and supply step stools).
    • Discuss adapting age-appropriate clothing with snapless easy-opening fasteners and tuckable loops.
    • Discuss adaptation of toys, especially tricycles, to accommodate short limbs.
    • Discuss adaptation of toilets to allow comfortable independent use, with an extended wand for wiping.
    • Discuss the use of a stool during sitting so that the child's feet are not hanging. Feet need support while the child is sitting in a chair. A cushion behind the child's back may be required for good posture.
    • Discuss orthodontic bracing in the future and the possible need for braces in children older than 5 years.
    • Encourage the family to develop activities in which the affected child can take part; avoid gymnastics, high diving, acrobatics, and collision sports.
    • Discuss how to talk with the child, friends, and family members about short stature.
    • Encourage preschool attendance so that the child can learn to socialize in an age-appropriate way, and work with parents to prepare the teacher and other children so that the child does not receive unnecessary special privileges.
    • Discuss toileting procedures and special preparations needed because of the child's short stature with school staff.
    • Discourage the child from jumping to decrease unnecessary stress on the joints and spine.
  •  Late childhood (5-13 y)
    • Discuss preparation of school personnel and furnishings to accommodate the child's stature.
    • Prepare the child for psychosocial situations, and teach the child how to discuss issues.
    • Be sure children can explain their short stature and can ask for help in an appropriate way.
    • Children with achondroplasia usually are included in the regular education program.
    • Suggest adaptive aids in the school to help the child cope with heavy doors, high doorknobs, blackboard use, and a regular-sized desk, and ask the school to provide foot support. In addition, be sure that the child can use the restroom independently.
  • Adolescence to early adulthood (13-21 y)
    • Revisit the diagnosis to ensure that the adolescent has command of the vocabulary and understanding of the diagnosis and genetic etiology of achondroplasia.
    • Discuss contraception and the options available. Women with achondroplasia are fertile and as such, reproductive options and potential for pregnancy outcomes and complications should be addressed.
    • Continue weight counseling to review the importance of weight control and eating habits to minimize the risk of obesity and the comorbid complications associated with excessive weight gain.
    • Assist the individual to establish an independent lifestyle. Fostering the ability to obtain a driver's license can help. Drivers require certain vehicle modifications, such as pedal extenders. The Association for Driver Rehabilitation Specialists (ADED) helps those who have certain transportation needs and vehicle adaptations.

Miscellaneous

Medicolegal Pitfalls

Preventing serious complications of achondroplasia involves taking a careful history and promptly referring the patient to appropriate subspecialists.

• Suspect possible cervicomedullary compression with a history of pain, ataxia, incontinence, and apnea. Evaluate the patient for brisk reflexes, a small foramen magnum, and central hypopnea, which are indications for surgery to release cord compression. Failure to recognize severe compression and to take appropriate measures thereafter can result in respiratory arrest and progressive quadriparesis.
• Patients with recurrent otitis media may need evaluation for language delay due to hearing loss.
• Sleep disturbances and an increasing occipitofrontal circumference (OFC) indicates referrals to appropriate subspecialists to address neurologic and respiratory abnormalities.

Special Concerns

• Pregnancy: Radiographic evaluation of the pelvis of a woman with achondroplasia is recommended before pregnancy to assess for narrow pelvis and to properly prepare for difficulties with vaginal delivery.

Multimedia

Media file 1: Height for females with achondroplasia (mean/standard deviation [SD]) compared to normal standard curves. The graph is based on information from 214 females. Adapted from Horton WA, Rotter JI, Rimoin DL, et al. Standard growth curves for achondroplasia. J Pediatr. 1978 Sep; 93(3): 435-8.

Media file 2: Height for males with achondroplasia (mean/2 standard deviations [SDs]) compared to normal standard curves. The graph is based on information from 189 males. Adapted from Horton WA, Rotter JI, Rimoin DL, et al: Standard growth curves for achondroplasia. J Pediatr. 1978 Sep; 93(3): 435-8.

Media file 3: Mean growth velocities (solid line) for males (top) and females (bottom) with achondroplasia compared to normal growth velocity curves. Dashed lines indicate third percentile, mean, and 97th percentile. Data are from 26 males and 35 females. Adapted from Horton WA, Rotter JI, Rimoin DL, et al. Standard growth curves for achondroplasia. J Pediatr. 1978 Sep; 93(3): 435-8.

Media file 4: Upper and lower segment lengths for males (top) and (bottom) with achondroplasia (mean/standard deviation [SD]). Data are from 75 males and 95 females. Adapted from Horton WA, Rotter JI, Rimoin DL, et al. Standard growth curves for achondroplasia. J Pediatr. 1978 Sep; 93(3): 435-8.

Media file 5: Head circumference for females with achondroplasia compared to normal curves (dashed lines). Data are from 145 females. Adapted from Horton WA, Rotter JI, Rimoin DL, et al. Standard growth curves for achondroplasia. J Pediatr. 1978 Sep; 93(3): 435-8.

Media file 6: Head circumference for males with achondroplasia compared to normal curves (dashed lines). Data are from 114 females. Adapted from Horton WA, Rotter JI, Rimoin DL, et al. Standard growth curves for achondroplasia. J Pediatr. 1978 Sep; 93(3): 435-8.

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Keywords

achondroplasia, short stature, chondrodysplasia, chondrodystrophy, skeletal dysplasia, osteochondrodysplasia, disproportionate short stature, short-limb dwarfism, hypotonia in infancy, megalencephaly, occipitofrontal circumference, OFC, midface hypoplasia, prominent forehead, frontal bossing, rhizomelic limbs, trident hands, brachydactyly, thoracolumbar gibbus, lumbar kyphosis, caudal narrowing of interpedicular spaces, lumbar lordosis, 4p16.3, fibroblast growth factor receptor-3 gene, FGFR3 gene, paternal age effect, autosomal dominant, treatment, diagnosis

Contributor Information and Disclosures

Author

Germaine L Defendi, MD, MS, FAAP, Associate Clinical Professor, Department of Pediatrics, Olive View-UCLA Medical Center
Germaine L Defendi, MD, MS, FAAP is a member of the following medical societies: Ambulatory Pediatric Association and American Academy of Pediatrics
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Medical Editor

James Bowman, MD, Senior Scholar of Maclean Center for Clinical Medical Ethics, Professor Emeritus, Department of Pathology, University of Chicago
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CME Editor

Paul D Petry, DO, FACOP, FAAP, Consulting Staff, Freeman Pediatric Care, Freeman Health System
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Bruce Buehler, MD, Professor, Department of Pediatrics, Pathology and Microbiology, Executive Director, Hattie B Munroe Center for Human Genetics, University of Nebraska Medical Center
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The authors and editors of eMedicine gratefully acknowledge the contributions of previous authors Joo-Hee Grace Park, DO and Robert Wallerstein, MD, to the original writing and development of this article.

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