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Osteochondrodysplasias involve abnormal bone or cartilage growth, leading to skeletal maldevelopment, often short-limbed dwarfism. Diagnosis is by physical examination, x-rays, and, in some cases, genetic testing. Treatment is surgical.
The basic genetic defects have been identified in most of the osteochondrodysplasias. The mutations typically cause perturbation of function in proteins involved in growth and development of connective tissue, bone, or cartilage (see Table 2: Connective Tissue Disorders in Children: Types of Osteochondrodysplastic Dwarfism ).
Dwarfism is markedly short stature (adult height < 4 ft 10 in) frequently associated with disproportionate growth of the trunk and extremities. Achondroplasia is the most common and best-known type of short-limbed dwarfism, but there are many other distinct types, which differ widely in genetic background, course, and prognosis (see Table 2: Connective Tissue Disorders in Children: Types of Osteochondrodysplastic Dwarfism). Lethal short-limbed dwarfism (thanatophoric dysplasia, caused by mutations in the same gene as achondroplasia) causes severe chest wall deformities and respiratory failure in neonates, resulting in death.
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Table 2
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| Types of Osteochondrodysplastic Dwarfism |
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Disorder
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Symptoms and Signs
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Usual Mode of Inheritance
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Defective gene product
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Achondroplasia
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Bulky forehead, saddle nose, lumbar lordosis, bowlegs
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AD
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Fibroblast growth factor receptor 3
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Chondrodysplasia punctata
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Variable extraskeletal manifestations
X-rays show epiphyseal stippling in infancy due to calcifications
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See below
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See below
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Chondrodysplasia punctata (rhizomelic form)
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Marked proximal limb shortening
Death during infancy
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AR
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Peroxisomal type 2 targeting signal receptor (PTS2)
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Chondrodysplasia punctata (Conradi-Hünermann form)
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Mild, asymmetric limb shortening
Benign
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AD or XL dominant
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Delta(8)-delta(7)-sterol isomerase emopamil-binding protein (EBP)
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Chondroectodermal dysplasia (Ellis–van Creveld [EVC] syndrome)
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Distal limb shortening, postaxial polydactyly, structural cardiac defects
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AR
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EVC, EVC2
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Diastrophic dysplasia
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Severe dwarfism with rigid hitchhiker thumb and fixed talipes equinovarum
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AR
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Solute carrier family 26 (sulfate transporter), member 2 (SLC26A2)
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Hypochondroplasia
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Symptoms of achondroplasia but milder
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AD
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Fibroblast growth factor receptor 3 (FGFR3—not all patients)
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Mesomelic dysplasia*
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Predominantly, shortening of the forearms and shanks
Normal facies and spine
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AD or AR
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Not defined
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Metaphyseal chondrodysplasia†
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In some forms, malabsorption, neutropenia, thymolymphopenia
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AR or AD
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Parathyroid hormone receptor (PTHR), type X collagen (COL10A1)
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Multiple epiphyseal dysplasia
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Mild dwarfism, normal spine and facies, sometimes stubby digits, hip dysplasia (often as 1st symptom)
Very heterogeneous
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AR or AD
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Solute carrier family 26 (sulfate transporter), member 2 (SLC26A2; AR form)
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Pseudoachondroplasia
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Normal facies, various degrees of dwarfism and kyphoscoliosis
Heterogeneous
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AD or AR
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Cartilage oligomeric matrix protein (COMP)
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Spondyloepiphyseal dysplasia
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Predominantly, kyphoscoliosis
Sometimes myopia and a flat facies
Heterogeneous
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AD, AR, or XL
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Type II collagen (COL2A1), tracking protein particle complex, subunit 2 (TRAPPC2, aka SEDL)
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*There are several eponymous forms (eg, Nievergelt, Langer).
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†There are many different eponymous forms (eg, Jansen, Schmid, McKusick).
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AD = autosomal dominant; AR = autosomal recessive; XL = X-linked.
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Diagnosis
Characteristic x-ray changes may be diagnostic. A whole-body x-ray of every affected neonate, even if stillborn, should be taken because diagnostic precision is essential for predicting prognosis. Prenatal diagnosis by fetoscopy or ultrasonography is possible in some cases (eg, when fetal limb shortening is severe). Standard laboratory tests do not help, but molecular diagnosis is feasible for chondrodysplasias with known molecular defects.
Treatment
In achondroplasia, treatment with human growth hormone is generally not effective. An increase in adult height may be achieved by surgical limb lengthening. In this and other nonlethal osteochondrodysplasias, surgery (eg, hip replacement) can help improve joint function. Hypoplasia of the odontoid process can predispose to subluxation of the 1st and 2nd cervical vertebrae and compression of the spinal cord. Therefore, the odontoid process should be evaluated preoperatively, and if it is abnormal, the patient's head should be carefully supported when hyperextended for endotracheal intubation during anesthesia.
Because the inheritance pattern in most types is known, genetic counseling can be effective. Organizations such as Little People of America (www.lpaonline.org) provide resources for affected people and act as advocates on their behalf. Similar societies are active in other countries.
Last full review/revision February 2008 by Frank Pessler, MD, PhD; David D. Sherry, MD
Content last modified February 2012
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