Skeletal Dysplasia

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Skeletal dysplasia


Skeletal dysplasias are a group of congenital abnormalities of the bone and cartilage that are characterized by short stature.


Skeletal dysplasia , sometimes called dwarfism, is a disorder of short stature defined as height that is three or more standard deviations below the mean height for age, race, and gender. Although all skeletal dysplasias involve disproportionately short stature, there are many other associated conditions.

Skeletal dysplasia may also have additional skeletal abnormalities, including:

  • short arms and truck, bowlegs, and a waddling gait
  • skull malformations, such as a large head, cloverleaf skull, craniosynostosis (premature fusion of the bones in the skull), and wormian bones (abnormal thread-like connections between the skull bone)
  • anomalies of the hands and feet, including polydactyly (extra fingers), "hitchhiker" thumbs, and abnormal finger and toe nails
  • chest anomalies, such as pear-shaped chest and narrow thorax

Other anomalies that may be present in individuals with skeletal dysplasia include:

  • anomalies of the eyes, mouth, and ears, such as congenital cataract, myopia (nearsightedness), cleft palate, and deafness
  • brain malformations, such as hydrocephaly, porencephaly, hydranencephaly, and agenesis of the corpus callosum
  • heart defects, such as atrial septal defect (ASD), patent ductus arteriosus (PDA), and transposition of the great vessels (TGV)
  • developmental delays and mental retardation

Skeletal dysplasia encompasses more than 200 different specific diagnoses. A list of some of the more common types of skeletal dysplasia includes achondrogenesis , achondroplasia , acrodystosis, acromesomelic dysplasia, atelosteogenesis, diastrophic dysplasia , chondrodysplasia punctata , fibrochondrogenesis hypochondrodysplasia, Kniest syndrome, Langer-type mesomelic dysplasia, micromelia, metaphyseal dysplasia , metatrophic dysplasia, Morquio syndrome, osteochondrodyspasia, osteogenesis imperfecta , Reinhardt syndrome, Roberts syndrome, Robinow syndrome , spondyloepiphyseal dysplasia congenital, spondyloepimetaphyseal dysplasia, and thanatophoric dysplasia .

Genetic profile

With more than 200 distinct skeletal dysplasias currently recognized, naming and categorizing these disorders is a significant task. In 1997, a standardized method for naming and classifying the skeletal dysplasias was proposed using information about the etiology of each disorder based on the genetic mutation or protein defect involved. Disorders that originate from similar or identical gene mutations were grouped together, and other categories were renamed in an attempt to create a more logical classification system. With so many unique disorders, categorizing the skeletal dysplasias will continue to evolve as new genetic mutations are identified.

Skeletal dysplasia refers to a group of disorders characterized by abnormalities of bone and cartilage with similar modes of transmission: autosomal dominant and recessive and X-linked dominant and recessive.

The following is a list of skeletal dysplasias with known genetic causes:

  • Achondroplasia group: These dysplasias are caused by mutations in the fibroblast growth factor 3 gene (FGFR3).
  • Diastrophic dysplasia group: This group is caused by mutations in the diatrophic dysplasia sulfate transporter gene (DTDST).
  • Type II collagenopathies: These are caused by mutations in the procollagen II gene (COL2A1).
  • Type XI collagenopathies: These dysplasias are caused by mutations in the procollagen XI genes (COL11A1 and COL11A2).
  • Multiple epiphyseal dysplasias and pseudoachondroplasia : These groups are caused by mutations in the cartilage oligomatrix protein gene (COMP).
  • Chondrodysplasia punctata: This complex group of skeletal dysplasias has several different types, each of which is caused by a unique genetic mutation. Chondrodysplasia punctata is caused by one of the following genetic mutations: arylsulfatase E gene (ARSE), X-linked dominant chondrodysplasia punctata gene (CPXD), X-linked recessive chondrodysplasia (CPDR), and genes responsible for production of the peroxisomal factors (PEX).
  • Metaphyseal dysplasias: Three different genetic mutations are responsible for the three types of this dysplasia: adenosine deaminase gene (ADA), the procollagen X gene (COL10A1), and the gene responsible for producing the parathyroid hormone/parathyroid hormone-related polypeptide receptor (PTHR).
  • Acromelic and acromesomelic dysplasias: These disorders are caused by genetic mutations in the genes responsible for encoding the cartilage-derived morphogenic protein-1 gene (CDMP 1) and the guanine nucleotide-binding protein of the edenylate cyclase a-subunit (GNAS1).
  • Dysplasia with prominent membranous bone involvement: This group is caused by a mutation of the transcription core binding a1-subunit gene (CBFA1).
  • Bent-bone dysplasia group: This group of dysplasias iscaused by mutations in the SRY-box 9 protein (SOX9).
  • Dysplasia with defective mineralization: This dysplasia is caused by the following gene mutations: the liver alkaline phosphatase gene (ALPL), the parathyroid calcium-sensing receptor gene (CASR), and the X-linked hypophsphatemia gene (PHEX).
  • Increased bone density without modification of bone shape: Mutations in the carbonic anhydrase II gene (CA2) and the cathepsin K (CTSK) cause these dysplasias.
  • Disorganized development of cartilaginous and fibrous components of the skeleton: These dysplasias are caused by several mutations, including abnormalities of the bone morphogenic protein 4 gene (BMP4), the guanine nucleotide-binding protein a-subunit gene (CNAS1), and exostosis genes (EXT1, EXT2, and EXT3).


Skeletal dysplasia is usually diagnosed at birth; however, some dysplasias may not be detected until much later. For this reason, it is difficult to determine the true incidence. The reported rate in the United States is one per every 4,000–5,000 births.

No one race is more likely to have skeletal dysplasia. The X-linked recessive disorders affect males almost exclusively, and X-linked dominant types are often lethal in males. Autosomal recessive and dominant transference affects males and females equally.

Signs and symptoms

The primary sign of skeletal dysplasia is abnormally shortened long bones in the legs and arms, short trunk, and abnormalities of the skull.

In addition to the skeletal system, skeletal dysplasia disorders may also affect the heart, the face, extremities, and joints.

Some forms are lethal, and a significant number of fetuses with skeletal dysplasia die in utero.


Many skeletal dysplasias can be diagnosed prenatally during routine prenatal ultrasound . If skeletal dysplasia is suspected, assessment and careful measurement of the extremities, thorax, spine, and facial structure can detect signs of the condition. Fetal movement may be decreased, and associated congenital heart and renal heart defects may be observed as well.

After birth, x rays are the most effective diagnostic tool for evaluating the skeleton. A skeletal study includes views of the long bone, hands and feet, skull, chest, spine, and pelvis.

Abnormal x-ray results that may indicate a skeletal dysplasia include:

  • dumbbell-shaped long bones
  • bowing of the arms and legs
  • oval-shaped translucencies in the femur and humerus
  • scapula hypoplasia (small shoulder blades)
  • abnormal pelvis
  • vertebral abnormalities
  • rib abnormalities, including cupping of the ends or shortening of the entire rib and stippled or spotted appearance to the cartilage
  • epiphyses (growth centers of the long bones) abnormalities, including cone shape, stippled appearance, or an absence of calcification centers
  • long bone fractures

Computed tomography (CT) scan and magnetic resonance imaging (MRI) are useful in assessing concurrent brain anomalies. MRI is useful in determining the extent and type of spinal abnormalities and compression present.

Three-dimension CT scan is used to evaluate craniofacial anomalies prior to reconstructive surgery. MRI of the spine is also helpful in pre-surgical planning prior to surgical treatment of spinal and pelvic abnormalities.

Chromosome analysis may be performed to help determine the type of skeletal dysplasia an individual has. This is important so that other associated conditions can be diagnosed and treated as well.

Other diagnostic procedures that may be performed, including molecular analysis to identify single gene mutations, sleep studies to evaluate potentially life-threatening sleep apnea that is often a problem for individuals with skeletal dysplasia, histological studies to examine specific types of cells that identify some skeletal dysplasia forms, and an echocardiogram (ECHO) to evaluate the heart for defects.

Treatment and management

Treatment and management of children with skeletal dysplasia begins, in some cases, at birth. Neonatal resuscitation may be necessary for infant with certain more severe types of skeletal dysplasia in which the thoracic cavity is extremely small. This intervention can be life-saving.

The medical management of children with skeletal dysplasia begins at birth and continues into adulthood. Careful monitoring of height, weight, and head circumference is essential. Obesity is a risk for those with skeletal dysplasia. Excess weight can cause serious complications, including breathing difficulties such as sleep apnea, and may aggravate other spinal cord compression and joint instability found in many types of skeletal dysplasia.

Surgical treatment of skeletal dysplasia varies depending on the specific type present and the associated conditions. Sleep apnea may be treated by removal of the adenoids.

Spinal abnormalities, such as spinal cord compression, scoliosis , kyphosis, and lordosis, may be treated surgically. A spinal column fusion can relieve the stress on the spinal cord caused by malformations of the spinal column. In a spinal fusion, two or more vertebrae are fused together using bone grafts or metal rods.

In some individuals with short-limbed types of skeletal dysplasia, bone growth may be induced by a surgical bone-lengthening procedure. This procedure involves several surgeries and an extensive recovery period. The bone to be lengthened is cut. Leaving a narrow gap between the two pieces of bone, metal pins are inserted into the bone and the skin is closed. An external frame is attached to the pins and, gradually, the bone is pulled apart just enough to provide a small gap for the bone to grow into. As the bone grows, the space is widened and more bone grows. After the bone has healed, the pins are surgically removed. In some cases, as much as 6 in (15 cm) has been added to leg length using this procedure.


While some skeletal dysplasias are lethal, most individuals with skeletal dysplasia have a normal life expectancy. The associated conditions may require medical and surgical treatment; however, these treatments are highly effective. Intelligence is usually normal. Most people with skeletal dysplasia have an excellent prognosis.



Rimoin, David, Ralph Lachman, and Shelia Unger. "Chrondfrodysplasia." In Emery and Rimion's Principles and Practice of Medical Genetics, 4th edition, edited by David L. Rimoin, J. Michael Connor, Reed Pyeritz, and Bruce R. Korf. London: Churchill Livingstone, 2002.


Committee on Genetics. "Health Supervision for Children with Achondroplasia." Pediatrics 95 (March 1995): 443–451.

Savarirayan, Ravi, and David L. Rimoin. "Skeletal Dysplasia." Advances in Pediatrics 51 (2004): 1–21.

Unger, Sheila. "A Genetic Approach to the Diagnosis of Skeletal Dysplasia." Clinical Orthopedics and Related Research 401 (2002): 32–38.


Little People of America. 5289 NE Elam Young Parkway, Suite F-100, Hillsboro, OR 97124. (888) LPA-2001 (English and Spanish), (503) 846-1562. Fax: (503) 846-1590. (April 13, 2005.) <>.

March of Dimes. 1275 Mamaroneck Ave., White Plaines, NY 10605. (April 13, 2005.) <>.

Human Growth Foundation. 997 Glen Cove Ave., Suite 5, Glen Head, NY, 11545. (800) 451-6434. (April 13, 2005.) <>.


Rhizomelic Chondrodysplasia Punctata (RCP) Family Support Group. (Accessed April 1, 2005; April 13, 2005.) <>.

Deborah L. Nurmi, MS