Osteochondrodysplasias (Osteochondrodysplastic Dwarfism)
(Genetic Skeletal Dysplasias)
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: 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: 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.
Types of Osteochondrodysplastic Dwarfism
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. Genetic testing is advised if a diagnosis cannot be made based on clinical grounds or if genetic counseling is desired.
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 and gene mutations in most types are known, genetic counseling can be effective. Organizations such as Little People of America provide resources for affected people and act as advocates on their behalf. Similar societies are active in other countries.
Osteochondrodysplasias are inherited abnormalities of growth and development of connective tissue, bone, and/or cartilage.
There are many types, which differ widely in genetic background, course, and prognosis, but all cause markedly short stature and often disproportionate growth of the trunk and extremities.
Diagnosis is by clinical manifestations and identification of characteristic x-ray changes.
Growth hormone treatments are typically ineffective.