Achondroplastic Dwarfism

Definition

Definition of Achondroplastic Dwarfism
Achondroplasia dwarfism occurs as a sporadic mutation in approximately 85% of cases (associated with advanced paternal age) or may be inherited in an autosomal dominant genetic disorder that is a common cause of dwarfism. Achondroplastic dwarfs have short stature, with an average adult height of 131 cm (4 feet, 3½ inches) for males and 123 cm (4 feet, ½ inch) for females.

Symptoms

Symptoms of Achondroplastic Dwarfism
A typical defining characteristic of dwarfism is an adult height of less than 147 cm (4 ft 10 in). Since those with dwarfism have such a wide range of physical characteristics, oddities in individuals are identified by diagnosing and monitoring the underlying disorders.

Disproportionate dwarfism is characterized by one or more body parts being disproportionately large or small compared to the rest of the body. In achondroplasia the trunk is normally sized with the limbs being disproportionately short, the head being larger than usual, and the forehead being prominent.Facial features are often affected and individual body parts may have problems associated with them. Orthopedic problems can result from multiple conditions such as diastrophic dysplasia and pseudoachondroplasia.

Proportionate dwarfism is marked by body parts being proportional but stunted. Height is significantly below average and there may be long periods without any significant growth. Sexual development is often delayed or impaired into adulthood. Unlike disproportionate dwarfism, mental capacity may be diminished in some cases of proportionate dwarfism. The overall stunted growth can lead to impaired intelligence when compared to the physical age.

Physical maleffects of malformed bones vary according to the specific disease. Many involve joint pain caused by abnormal bone alignment, or from nerve compression (e.g., spinal stenosis). Early degenerative joint disease, exaggerated lordosis or scoliosis, and constriction of spinal cord or nerve roots can cause pain and disability. Reduced thoracic size can restrict lung growth and reduce pulmonary function. Some forms of dwarfism are associated with disordered function of other organs, such as the brain or liver, sometimes severely enough to be more disabling than the abnormal bone growth.

Causes

Causes of Achondroplastic Dwarfism
Dwarfism is a result of autosomal dominant mutation in the fibroblast growth factor receptor gene 3 , which causes an abnormality of cartilage formation. In normal circumstances, FGFR3 has a negative regulatory effect on bone growth. In achondroplasia, the mutated form of the receptor is constitutively active and this leads to severely shortened bones.

People with achondroplasia have one normal copy of the fibroblast growth factor receptor 3 gene and one mutant copy. Two copies of the mutant gene are invariably fatal before or shortly after birth. Only one copy of the gene has to be present for the disorder to occur. Therefore, a person with achondroplasia has a 50% chance of passing on the gene to his or her offspring, meaning that there will be a 50% chance that each child will have achondroplasia. Since it is fatal to have two copies (homozygous), if two people with achondroplasia have a child, there is a 25% chance of the child dying shortly after birth, a 50% chance the child will have achondroplasia, and a 25% chance the child will have an average phenotype. People with achondroplasia can be born to parents that do not have the condition. This is the result of a new mutation.

Diagnosis

Diagnosis of Achondroplastic Dwarfism
Achondroplasia can be detected before birth by the use of prenatal ultrasound. A DNA test can be performed before birth to detect homozygosity, wherein two copies of the mutant gene are inherited, a lethal condition leading to stillbirths.

A skeletal survey is useful to confirm the diagnosis of achondroplasia. The skull is large, with a narrow foramen magnum, and relatively small skull base. The vertebral bodies are short and flattened with relatively large intervertebral disk height, and there is congenitally narrowed spinal canal. The iliac wings are small and squared, with a narrow sciatic notch and horizontal acetabular roof. The tubular bones are short and thick with metaphyseal cupping and flaring and irregular growth plates. Fibular overgrowth is present. The hand is broad with short metacarpals and phalanges, and a trident configuration. The ribs are short with cupped anterior ends. If the radiographic features are not classic, a search for a different diagnosis should be entertained. Because of the extremely deformed bone structure, people with achondroplasia are often double jointed.

The diagnosis can be made by fetal ultrasound by progressive discordance between the femur length and biparietal diameter by age. The trident hand configuration can be seen if the fingers are fully extended.

Prognosis

Prognosis of Achondroplastic Dwarfism
The prognosis of people with achondroplasia dwarfism depends on the severity of their condition. In 2 to 5 percent of all cases, newborns do not survive more than 12 months after birth. These cases are considered to be a severe form of achondroplasia dwarfism. However, most people with the condition should expect to live a normal lifespan and have normal intelligence.

Treatment

Treatment of Achondroplastic Dwarfism
At present, there is no known treatment for achondroplasia.

Although used by those without achondroplasia to aid in growth, human growth hormone does not help people with achondroplasia. However, if desired, the controversial surgery of limb-lengthening will lengthen the legs and arms of someone with achondroplasia.

Usually, the best results appear within the first and second year of therapy. After the second year of GH therapy, beneficial bone growth decreases. Therefore, GH therapy is not a satisfactory long term treatment.