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Achondroplasia

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Achondroplasia is a common type of dwarfism.


Presentation

Achondroplasia is present at birth and is seen as disproportionately short-limbs, and specific facial features due to abnormal bone growth. Infants with achondroplasia suffer a high rate of apnea and sudden death in the neonatal period [12]. The principle features of achondroplastic dwarfism include [2] [7] [11] [13]:

  • Rhizomelic (proximal) shortening of the extremities with normal trunk size
  • Decreased growth of the long bones of the proximal extremities (humerus and femur)
  • Macrocephaly 
  • Abnormal development of the base of the skull with narrowing of the foraman magnum
  • Under-development of the mid-face
  • Stenosis of the spinal canal and intervertebral foramen
  • Genu varum

Macrocephaly is often present due to triventricular enlargement and hydrocephalus may result [8] [11]. However, intracranial pressure is not elevated significantly [8] [9]. The distinctive facial features include [3] [11]:

Achondroplasia is a short-limb dwarfism. These individuals have a sitting height that is normal, while standing height is below the third percentile. The mean adult standing height for men is 132 cm (52 in), and that for women is 125 cm (49 in) [3] [11]. The upper arms and thighs are more severely involved than the forearms, legs, hands, and feet [3]. There is normal development of clavicle and musculature resulting in broad, strong shoulders. The anterior-posterior chest diameter is flattened, lower ribs flared, and the abdomen protrudes [3] [11].

Complications associated with achondroplasia include [3] [9] [11] [14]:

Respiratory complications

The most serious complications of achondroplasia are restrictive respiratory disease, apnea, pneumonia, and sudden infant death resulting from compression of the medulla oblongata [3] [12]. The prevalence of respiratory complications in this population is reported to be 12% versus 0.92% in the general population [12]. Pneumonia remains a primary cause of death [12].

Neurologic complications

Half of the patients with achondroplasia show neurological complications [2] [9]. Abnormal development of the base of the skull results in compression of the cervicomedullary region. Affected individuals also have smaller foramen magnum dimensions and abnormal shape [9] [11] [13]. These two conditions may cause respiratory insufficiency, apnea, cyanotic episodes, feeding problems, quadriparesis, and sudden death [9].

Spinal deformities are the most common and potentially disabling problems seen in achondroplasia [9] [11]. Stenosis of the spinal canal and intervertebral foramen can result in sensory deficits, lower and upper motor neuron involvement which result in low back pain, leg pain, dysesthesia, paresthesia, paraparesis, and incontinence [9]. 

Narrowing of the foramen magnum may result in a variety of neurologic problems in the first several years of life particularly [4] [9] [11]. It is the primary factor responsible for respiratory problems and sudden infant death of infants with achondroplasia in the neonatal period [4].

Abnormal curvature of the spine (kyphosis, lordosis, scoliosis) is present in 33-50% of adults with achondroplasia [9] [11]. It may cause back pain, respiratory dysfunction, neurologic deficits, or symptoms of spinal stenosis [9]. These abnormalities generally do not require treatment [10].

Developmental issues

In achondroplasia children milestones are delayed across all ages and domains compared with the general population [3] [14]. Children up to 7 years of age have a greater need for caregiver assistance in all areas [14]. Functional delays are related to musculoskeletal impairments [3] [14]. Head control, sitting, standing, and ambulation may lag by 3-6 months [8][14]. Children with achondroplasia show improvement in functioning with physical therapy between the ages of 3 and 5 years, but not after this [14].

Speech and language problems are common with achondroplasia. They are caused by tongue thrust that usually resolve spontaneously [8] [14]. Cognitive development and the intelligence levels in these children are generally normal [8] [14].

Recurrent otitis media is common due to poor drainage of the Eustachian tubes from underdevelopment of the mid-face. This may result in moderate to severe hearing loss [3] [10].

Obesity is a lifelong issue for affected individuals. As a result these individuals are at higher risk of chronic diseases such as diabetes and cardiovascular disease [3] [10]. These conditions have a direct causal relationship with early mortality rates due to stroke and myocardial infarction [10].

Short Finger
  • ; fingers are stubby Average adult height is about 4 feet tall Achondroplasia 1.[slideshare.net]
  • In those afflicted with the disorder, the limbs are very short (fingers reach only to the hips), but the trunk is almost normal in size.[britannica.com]
  • fingers Trident hand, a condition in which you have an extra space between the middle and ring fingers Weak muscle tone.[babymed.com]
  • People who have achondroplasia have abnormal bone growth that causes the following clinical symptoms: short stature with disproportionately short arms and legs, short fingers, a large head (macrocephaly) and specific facial features with a prominent forehead[genome.gov]
Developmental Delay
  • delay and acanthosis nigricans).[ncbi.nlm.nih.gov]
  • delay and acanthosis nigricans (SADDAN), and thanatophoric dysplasia (TD).[ncbi.nlm.nih.gov]
  • An 8-year-old female was diagnosed with a developmental delay, known as achondroplasia, seven months after birth. Upon her initial visit, visual acuity was 0.3 in both eyes. The patient had telecanthus but normal ocular motility.[ncbi.nlm.nih.gov]
  • Cord compression at the level of the foramen magnum can be encountered in infancy and early childhood causing central apnea, developmental delay, and long-track signs. Genu varum often occurs in childhood.[orpha.net]
Recurrent Otitis Media
  • Recurrent otitis media is common due to poor drainage of the Eustachian tubes from underdevelopment of the mid-face. This may result in moderate to severe hearing loss.Obesity is a lifelong issue for affected individuals.[symptoma.com]
  • Clinical Findings Delayed motor development Recurrent otitis media Normal intelligence Short stature Lower extremity radiculopathy Imaging Findings Can be detected before birth by the use of prenatal ultrasound After birth, conventional radiography is[learningradiology.com]
  • Morbidity associated with acondroplazia may include: recurrent otitis media with hearing loss, neurological complications cervicomedulara compression (hypotonia, respiratory insufficiency, apnea, cyanotic episodes, problems of nutrition, cvadripareza,[medicaldb.blogspot.com]
Short Stature in Children
  • The most common reasons for short stature in children are familial short stature, a difference in the timing of growth (called constitutional growth delay) and, in girls, Turner syndrome.[gemssforschools.org]
Pneumonia
  • Pneumonia remains a primary cause of death. Neurologic complications Half of the patients with achondroplasia show neurological complications. Abnormal development of the base of the skull results in compression of the cervicomedullary region.[symptoma.com]
  • Care should be taken to avoid respiratory complications such as pauses in breathing (apnea) and pneumonia. Obesity is frequently seen in patients of achondroplasia. Therefore, diet should be regulated since from the early years of life. References :[healthhype.com]
  • […] complications due to cervicomedullary compression (eg, hypotonia, respiratory insufficiency, apnea, cyanotic episodes, feeding problems, quadriparesis, sudden death) [1] Obstructive and restrictive respiratory complications (eg, upper airway obstruction, pneumonia[emedicine.medscape.com]
  • Other complications include pneumonia, apnea, spinal deformities, obesity, hidrocefalus, genu varum. Somatropin has revolutionized the treatment of small stature. Growth hormone is now used to enlarge the height acondroplazie patients.[medicaldb.blogspot.com]
  • […] excavatum and kyphoscoliosis [ 6 ] of the thoracic spine causes restrictive lung disease resulting in decreased FRC, increase closing volume, atelectasis and on long term obstructive and central sleep apnoea, cor pulmonale and increase postoperative pneumonia[omicsonline.org]
Cyanosis
  • Sleep-related symptoms (snoring, mouth breathing, cyanosis, observed apneas, excessive sweating, enuresis, problems of initiating and maintaining sleep) were present in 18/24 patients (75%).[ncbi.nlm.nih.gov]
Hearing Problem
  • Treatment of ear infections and serous otitis media, along with assessment of any hearing problems is needed. Speech therapy can be offered if concerns arise.[orpha.net]
Skeletal Dysplasia
  • In the homozygous state, these variant results in a severe skeletal dysplasia, neurologic deficits, and early demise from respiratory insufficiency.[ncbi.nlm.nih.gov]
  • PURPOSE OF REVIEW: The goal of this review is to evaluate the management options for achondroplasia, the most common non-lethal skeletal dysplasia.[ncbi.nlm.nih.gov]
  • Achondroplasia is the most common inherited disorder of bone growth (skeletal dysplasia).[ncbi.nlm.nih.gov]
  • The aim of our study was to review the poly(somno)graphic (P(S)G) findings and consequent treatments in children with achondroplasia followed in the national reference center for skeletal dysplasia.[ncbi.nlm.nih.gov]
  • We propose that meclozine is a potential therapeutic agent for treating ACH and other FGFR3-related skeletal dysplasias.[ncbi.nlm.nih.gov]
Lordosis
  • Bony characteristics such as vertebral anomalies, lordosis and lumbar scoliosis, limited mouth opening and cervical spine instability make the administration of anesthesia to these patients truly a challenge.[ncbi.nlm.nih.gov]
  • Radiographic examination showed typical findings of achondroplasia, such as disproportionately large skull, shortening of limb segments, and lumbar lordosis. FGFR3 screening showed a heterozygous G1138A mutation.[ncbi.nlm.nih.gov]
  • Affected individuals exhibit short stature caused by rhizomelic shortening of the limbs, characteristic facies with frontal bossing and mid-face hypoplasia, exaggerated lumbar lordosis, limitation of elbow extension, GENU VARUM, and trident hand.[fpnotebook.com]
  • […] bossing ) Shortened arms and legs (especially the upper arm and thigh) Short stature (significantly below the average height for a person of the same age and sex) Narrowing of the spinal column ( spinal stenosis ) Spine curvatures called kyphosis and lordosis[nlm.nih.gov]
  • Achondroplasia can cause health complications such as apnea, obesity, recurrent ear infections, and lordosis of the spine. Achondroplasia is caused by mutations in the FGFR3 gene. It is inherited in an autosomal dominant fashion.[diseaseinfosearch.org]
Back Pain
  • A 61-year-old man with a history of achondroplastic dwarfism presented with low back pain and radiculopathy and neurogenic claudication.[ncbi.nlm.nih.gov]
  • It may cause back pain, respiratory dysfunction, neurologic deficits, or symptoms of spinal stenosis. These abnormalities generally do not require treatment.[symptoma.com]
  • Older individuals often have back pain, which can cause difficulty with walking. How common is achondroplasia? Achondroplasia is the most common type of short-limbed dwarfism. The condition occurs in 1 in 15,000 to 40,000 newborns.[babymed.com]
  • The problems with the lower back can cause back pain leading to difficulty with walking. How is achondroplasia diagnosed? Achondroplasia is diagnosed by characteristic clinical and X-ray findings in most affected individuals.[genome.gov]
  • Luckily, Marco is safe from some of the health problems that achondroplasia patients usually deal with: breathing difficulties (apnea), recurrent ear infections, back pain, lack of stability, or spinal stenosis .[eurordis.org]
Short Arm
  • Short arms and legs, with particularly short upper arms and thighs. An enlarged head (macrocephaly), with a prominent forehead. Fingers that are typically short.[bones.emedtv.com]
  • Short stature Short arms and legs (particularly short upper arms and thighs) Limited range of movement in elbows Trident hand (i.e. ring finger and middle finger may diverge) Macrocephaly (enlarged head with prominent forehead) Midfacial retrusion and[littlepeopleuk.org]
  • This causes a series of signs, such as short arms and legs and a large head. This condition used to be called dwarfism. A boy with the condition will reach an average adult height of about 4 feet, 4 inches (52 inches).[urmc.rochester.edu]
Macrocephaly
  • Achondroplasia is an autosomal dominant disease which is characterized by limb shortening and narrow trunk, and macrocephaly. Women with achondroplasia suffer from infertility, menorrhagia, dysmenorrhoea, leiomyomata and early menopause.[ncbi.nlm.nih.gov]
  • The diagnosis of achondroplasia is based on typical clinical and radiological features including short stature, macrocephaly with frontal bossing, midface hypoplasia and rhizomelic shortening of the limbs.[ncbi.nlm.nih.gov]
  • The clinical and radiological features of achondroplasia can easily be identified; they include disproportionate short stature with rhizomelic shortening, macrocephaly with frontal bossing, midface hypoplasia, lumbar hyperlordosis, and a trident hand[ncbi.nlm.nih.gov]
  • Airway anatomy is problematic due to macrocephaly, midface hypoplasia, and a narrow nasopharynx. Manipulation of the neck is very dangerous due to the high likelihood of preexisting cervicomedullary stenosis.[ncbi.nlm.nih.gov]
  • These clinical findings include: shortened limbs especially of upper arms and legs, macrocephaly, abnormally shaped skull, flat face and abnormal maxilla. The particular pattern of long-bone growth is specific to achondroplasia.[symptoma.com]
Frontal Bossing
  • Abstract Achondroplasia is an autosomal dominant disorder characterized by disproportionately short stature, frontal bossing, rhizomelia, and trident hands.[ncbi.nlm.nih.gov]
  • A prenatal 3-D helical CT revealed a large head with frontal bossing, metaphyseal flaring of the long bones, and small iliac wings, which suggested achondroplasia.[ncbi.nlm.nih.gov]
  • The diagnosis of achondroplasia is based on typical clinical and radiological features including short stature, macrocephaly with frontal bossing, midface hypoplasia and rhizomelic shortening of the limbs.[ncbi.nlm.nih.gov]
  • The clinical and radiological features of achondroplasia can easily be identified; they include disproportionate short stature with rhizomelic shortening, macrocephaly with frontal bossing, midface hypoplasia, lumbar hyperlordosis, and a trident hand[ncbi.nlm.nih.gov]
  • The other orocraniofacial features include enlarged calvarium, prominent forehead and frontal bossing, midface hypoplasia, elongated lower face and saddle-shaped nose due to lack of development of the nasomaxillary complex.All our patients had a typical[ncbi.nlm.nih.gov]
Mid-Face Hypoplasia
  • Affected individuals exhibit short stature caused by rhizomelic shortening of the limbs, characteristic facies with frontal bossing and mid-face hypoplasia, exaggerated lumbar lordosis, limitation of elbow extension, GENU VARUM, and trident hand.[fpnotebook.com]
  • Beyond disproportionate short stature, people with achondroplasia can experience serious health complications, including foramen magnum compression, sleep apnea, bowed legs, mid-face hypoplasia, permanent sway of the lower back, spinal stenosis, recurrent[biomarin.com]
  • Affected individuals exhibit short stature caused by rhizomelic shortening of the limbs, characteristic facies with frontal bossing and mid-face hypoplasia, exaggerated lumbar lordosis, limitation of elbow extension, genu varum, and trident hand.[icd10data.com]
Incontinence
  • Neurosurgical symptoms that may indicate the need for corrective surgery include back pain, muscle weakness, incontinence, hypotonia, psychomotor delay, apnea, and respiratory arrest.[symptoma.com]
  • Search: Home Bath Safety Braces Impotence & Male ED Incontinence Mobility Shop By Categories Shop by Topic Gift Ideas Respiratory Miscellaneous Home Bath Safety Bath Lifts Bathing Aids - Hygiene Bidet Toilet Seats Commodes and Accessories Grab Bars Shower[activeforever.com]
  • Foramen magnum stenosis which may lead to cervicomedullary compression and central apneas Lumbar spinal stenosis which can lead to neurologic deficits such as claudication and incontinence Thoracic deformities may cause restrictive lung disease [4] Medical[physio-pedia.com]
Dysesthesia
  • Stenosis of the spinal canal and intervertebral foramen can result in sensory deficits, lower and upper motor neuron involvement which result in low back pain, leg pain, dysesthesia, paresthesia, paraparesis, and incontinence.[symptoma.com]
Paresthesia
  • Stenosis of the spinal canal and intervertebral foramen can result in sensory deficits, lower and upper motor neuron involvement which result in low back pain, leg pain, dysesthesia, paresthesia, paraparesis, and incontinence.[symptoma.com]
Dysesthesia
  • Stenosis of the spinal canal and intervertebral foramen can result in sensory deficits, lower and upper motor neuron involvement which result in low back pain, leg pain, dysesthesia, paresthesia, paraparesis, and incontinence.[symptoma.com]

Workup

Diagnosis of achondroplasia is made based on physical examination and genetic testing [3] [10]. Early identification of the disorder is generally made either prenatally or in early infancy by the presence of the distinctive features of the disease [3]. These clinical findings include: shortened limbs especially of upper arms and legs, macrocephaly, abnormally shaped skull, flat face and abnormal maxilla [2]. The particular pattern of long-bone growth is specific to achondroplasia [2] [11].

Diagnosis of achondroplasia may also be made using prenatal ultrasonography to detect the skeletal abnormalities. However changes in limb lengths do not occur until 20-24 weeks’ gestation, after this time the growth rate decreases [2] [3].

Laboratory studies

Recent advances in molecular biology has made cell free fetal deoxyribonuleic acid (DNA) analysis allows genetic diagnosis of this condition using a maternal blood sample [2]. Analysis of plasma for the fibroblast growth factor receptor 3 (FGFR3) mutation in the mother can be done when a short-limb skeletal dysplasia is diagnosed prenatally on ultrasound [3] [7].

Imaging studies [10] [11]

  • Radiography: X-rays of individuals with achondroplasia show the characteristic features of the disease.
  • Ultrasonography of brain in the neonate can detect ventricle size and other abnormalities [9].
  • Computed tomography of brain, skull, trunk,and rib cage.
  • Magnetic resonance imaging evaluation is needed in any patient with neurological symptoms [9] [10]. A baseline scan is strongly recommended in infancy to evaluate potential problems [10]. 

Other tests when indicated [9] [10]:

  • Pulmonary function tests are indicated when respiratory symptoms are present. These show the vital capacity decreased by 68% for males and 72% for females.
  • Sleep apnea studies are useful in those with sleep hypoxia
  • Intracranial pressure monitoring with moderate ventriculomegaly. Treatment is recommended when the ICP is greater than 15 mm. 
  • Somatosensory evoked potential (SSEP) as abnormalities have been reported in 44% of patients with Achondroplasia.

Further evaluation of individuals with achondroplasia should include consultation by [8] [10]:

  • Geneticist
  • Neurologist, neurosurgeon
  • Pulmonary specialist
  • Orthopedist
  • Rehabilitation physiatrist
  • Speech therapist

Treatment

There is no specific treatment for achondroplasia at this time. Prenatal gene therapy is still in the future. Current therapy is essentially supportive to prevent the common complications associated with the disease [3] [10]. Therapeutic strategies are aimed at reducing fibroblast growth factor receptor 3 signals, such as kinase inhibitors and neutralizing antibodies [3] [6]. Administration of C-type natriuretic peptide is currently in the early stages of development. Further research into long-term effectives and safety of this drug is needed [3] [6].

Growth hormone is used to increase the height of patients with achondroplasia. There is no long-term data about the routine use of growth hormone and it remains controversial [3] [6]. There may be metabolic effects on the patient's lipid profile, bone mineral density, and muscle mass, and cardiovascular risk [6]. Somatotropin, a recombinant human growth hormone, for the treatment of short stature has shown acceleration in growth, particularly in the first year of treatment. It is recommended that therapy be started between age 1 to 6 years for maximum benefits [6].

Early identification and immediate cervicomedulary decompression procedure are needed to prevent serious neurological complications occurring in achondroplasia. These complications include respiratory failure, apnea and sudden death [9] [10].

Neurosurgical symptoms that may indicate the need for corrective surgery include back pain, muscle weakness, incontinence, hypotonia, psychomotor delay, apnea, and respiratory arrest [9][10].

Surgical procedures [3] [9] [10]:

Children with achondroplasia require more assistance for self-care and mobility skills. Interventions in this area should include physical therapy, occupational therapy, and speech therapy [8][14].

Obesity is a common complication in individuals with achondroplasia [15]. Obesity increases the risk for health problems such as cardiovascular disease and diabetes [5].

Prognosis

Overall survival and the average life expectancy for those with achondroplasia are decreased by approximately 10 years from the general population, despite advances in the knowledge of and health care needs [4] [10]. Early mortality generally results from the effects of skeletal and neurologic deformities, and is due to respiratory or cardiovascular complications [9].

The risk of producing a second affected child is negligible with a 1 in 443 risk of recurrence in the siblings of an affected child with unaffected parents [3] [7]. Normal sized siblings have no increased risk of producing a child with achondroplasia [7].

When both parents have achondroplasia [3] [7]:

  • 50% of their offspring are heterozygous and affected
  • 25% are homozygous which is usually fatal in the first few months of life
  • 25% are unaffected

If DNA testing shows the gene mutation present in both parents their infants have a 50% risk of inheriting affected genes from both parents (double homozygous). They are either stillborn or die shortly after birth [7].

Etiology

The term achondroplasia, though inaccurate, means absence of cartilage. It was first used by Parrot in 1878 [3]. Achondroplasia is the most common osteochondrodysplasia, a genetic disorder which is associated with abnormal bone growth at the growth plates [3] [7] [8]. The mode of inheritance is autosomal dominance, however, most cases represent as a new mutation [6] [8].

The genetic defect responsible for achondroplasia has been known for over a decade [3]. More than 95% of patients have a mutation in the gene for fibroblast growth factor receptor 3 (FGFR3) [3] [7]. This gene is responsible for the transmission of the signal to stimulate bone growth. Without this activation, individuals with achondroplasia fail to grow, particularly, the long bones of the proximal extremities [7].

Achondroplasia is associated with a number of life-threatening complications [8] [9]. No effective treatments to stimulate bone growth have been found [3] [6]. Life-expectancy for those with achondroplasia continues to be 10 or more years shorter than the general population [4]. The causes of death for these individuals are related to the complications associated with the skeletal deformities and their impact on the neurologic and cardiovascular systems [3] [4] [9].

In children younger than 4 years, brain stem compression is the most common cause of death [4]. In those 5-24 years of age, the common causes of mortality are central nervous system and respiratory problems [4]. In persons aged 25-54 years, cardiovascular problems are the most frequent causes of death [4].

The complexity of the condition led to the development of Heath Supervision Guidelines published by the American Academy of Pediatrics in 1995 and revised in 2005 [8] [10].

Epidemiology

The prevalence of achondroplasia is estimated to be approximately 10,000 individuals in the United States and 150,000 to 250,000 worldwide [3]. The incidence of achondroplasia is 5–15 per 100 000 live births [2] [4].

Achondroplasia affects all races [2]. It occurs with equal frequency in males and females [2].
More than 95% of patients have a mutation in the gene for fibroblast growth factor receptor 3 [3]. 

Higher death rates when adjusted for age are seen in the affected population [4]. Heart disease-related mortality, between ages 25 and 35, is more than 10 times higher than the general population [4].

Sex distribution
Age distribution

Pathophysiology

The skeleton is divided into 2 parts, the axial skeleton, or central core unit, and the appendicular skeleton, the bones of the extremities [11]. The primary defect of achondroplasia is abnormal endochondral ossification of the appendicular skeleton [8] [11].

The molecular basis for achondroplasia is related to the fibroblast growth factors which are stimulate cell growth and migration, wound healing, and angiogenesis [7]. The cause of the disorder is a mutation of the fibroblast growth factor receptor 3 (FGFR3) [7] [3] located on the fourth chromosome [2]. The primary function of fibroblast growth factor receptor 3 is to limit osteogenesis [2] [7]. Fibroblast growth factor receptors transmit a mitogenic signal that is unique to growth plate chondrocytes [3] [7]. The mutation negatively regulates chondrocyte production and differentiation by suppressing mitogenic activity [9]. Recent research suggests that the disorder is due to increased signal transduction from the mutant receptor resulting in the failure of cell production and growth at the growth plate [2] [3].

The genetic abnormality responsible for achondroplasia is a single gene mutation on the short arm of the fourth chromosome [2]. It can be transmitted as an autosomal dominant trait or as a new random mutation [2] [3]. Eighty percent of cases are the result of a new mutation which is linked to a paternal age over 36 years [2] [7]. Most parents are of normal size with no family history of a dwarfism [2].

Prevention

Most serious complications of achondroplasia can be prevented or reduced by anticipation and early treatment [3] [10]. Early neurological evaluation and intervention when indicated are required to prevent the high morbidity and mortality in infancy and childhood [9].

Little People of America is an excellent resource for individuals with achondroplasia. This national organization deals with the social, physical, and medical needs of this population.

Summary

Achondroplasia is the most common type of short-limb skeletal dysplasia [1] [2]. It is a form of dwarfism characterized by intrinsic abnormalities in the growth of cartilage and bone [3] [4]. It causes short stature (dwarfism) with a standing height below the third percentile for age [4]. Achondroplasia accounts for 80% of all individuals recognized as "little people" [3]. It has an estimated worldwide prevalence of 250,000 [4] [5].

Achondroplasia is a genetically inherited disease caused by a gene mutation of the fibroblast growth factor receptor 3 (FGFR3) [6]. This gene mutation affects the cartilaginous growth plate of the growing skeleton [3] [7]. It can result in a variety of deformities and complications [3].

The disorder can be transmitted as an autosomal dominant disease from either or both parents [3] [7]. However, in 80% of affected infants it occurs as a new sporadic mutation, the highest incidence of which occur with fathers over 40 years of age [3].

The life expectancy of individuals with achondroplasia is significantly lower than those not affected [3] [4]. Achondroplasia is associated with a number of life-threatening complications related to its skeletal abnormalities [4] [8]. Early mortality is the result of complications due to skeletal deformities causing restrictive respiratory disease, neurologic deficits, and cardiovascular problems [4] [9].

Patient Information

What is achondroplasia?

Achondroplasia is a form of dwarfism characterized by shortened extremities with near normal trunk length. It is accompanied by a larger than normal head and specific, distinctive facial features. It is present at birth and accounts for a high rate of deaths in the neonatal period and early infancy. In those individuals with Achondroplasia, who survive early childhood, life expectancy is generally shorter due to cardiovascular and respiratory complications.

What causes achondroplasia?

Achondroplasia is a genetically inherited disorder due to a mutation on the gene that controls bone growth at the growth plates of the long bones. It affects primarily the long bones of the upper arms and legs, the rib cage, and the bones of the base of the skull and face.

What are the symptoms?

Decreased growth of the long bones of the extremities ( humerus and femur),

  • Abnormal development of the base of the skull
  • Narrowing of the spinal canal
  • Under-development of the mid-face with characteristic features
  • Macrocephaly (enlarged head)

Who gets Achondroplasia?

Achondroplasia is an inherited genetic disorder. Individuals with this disease inherit it from either one or both of their parents. The majority inherit it due to a new, mutation in the gene from one parent (paternal age over 40 years has been associated with a high incidence of achondroplasia).
Parents generally are of normal height.

How is it diagnosed?

Achondroplasia is usually diagnosed by its characteristic skeletal features seen at birth or on prenatal ultrasound. Definitive diagnosis is made by the presence of the gene mutation on DNA analysis.

What are the complications?

The complications of achondroplasia are related to the skeletal deformities associated with the disease and include:

How is achondroplasia treated?

There is no specific treatment at this time. Research is being done on genetic interventions to overrule the effects of the gene mutation. The individual with achondroplasia is currently treated to prevent the life threatening complications of the disease. Early intervention and treatment to prevent neurologic and respiratory defects and prevention of obesity will hopefully extend the life expectancy of these individuals.

How can achondroplasia be prevented?

Achondroplasia cannot be prevented currently, however, research is being done involving gene therapy. Genetic counseling and prenatal testing can predict the disorder. Most serious complications can be prevented or reduced by anticipation and early treatment. Early neurological evaluation and intervention, when indicated, can prevent the high morbidity and mortality in infancy and childhood.

References

Article

  1. Achondroplasia. (2015). In Encyclopædia Britannica. 
  2. Chitty LS, Griffin DR, Meaney C, Barrett A, Khalil A, Pajkrt E, J. Cole T. New aids for the non-invasive prenatal diagnosis of achondroplasia: dysmorphic features, charts of fetal size and molecular confirmation using cell-free fetal DNA in maternal plasma. Ultrasound Obstet Gynecol . 2011; 37: 283–289.
  3. Horton WA, Hall JG, Hecht JT. Achondroplasia. Lancet. 2007;370(9582):162-72. 
  4. Wynn J, King TM, Gambello MJ, Waller DK, Hecht JT. Mortality in achondroplasia study: A 42-year follow-up. Am J Med Genet A. 2007;143(21):2502-11. 
  5. Hoover-Fong JE, Schulze KJ, McGready J, Barnes H, Scott CI. Age-appropriate body mass index in children with achondroplasia: interpretation in relation to indexes of height. Am J Clin Nutr. 2008;88(2):364-71. 
  6. Mehta A, Hindmarsh PC. The use of somatropin (recombinant growth hormone) in children of short stature. Paediatr Drugs. 2002;4(1):37-47. 
  7. Wang Q, Green RP, Zhao G, Ornitz DM. Differential regulation of endochondral bone growth and joint development by FGFR1 and FGFR3 tyrosine kinase domains. Development. 2001;128(19):3867-76. 
  8. Ireland PJ, Johnson S, Donaghey S, Johnston L, Ware RS, Zankl A, et al. Medical management of children with achondroplasia: Evaluation of an Australasian cohort aged 0-5 years. J Paediatr Child Health. 2012:48(5);443-9. 
  9. Gil Z, Tauman R, Sivan J, et al. Neurosurgical aspects in achondroplasia: evaluation and treatment. Harefuah. 2001;140(11):1026-31, 1118.
  10. American Academy of Pediatrics Committee on Genetics. Health supervision for children with achondroplasia. Pediatrics. 1995;95(3):443-51. 
  11. Smoker WR, Khanna G. Imaging the craniocervical junction. Childs Nerv Syst. 2008;24(10):1123-45.

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Last updated: 2019-07-11 22:02