What is Achondroplasia ?

Achondroplasia is a genetic disorder of bone growth that is evident at birth. It affects about one in every 20,000 births and it occurs in all races and in both sexes. The term achondroplasia is derived from the Greek meaning “without cartilage formation.” All the symptoms of the disease relate to the defect in the cartilage tissue. During fetal development and childhood, cartilage normally develops into bone, excep in a few places, such as the nose and the ears. In individuals with achondroplasia, something goes wrong with this process, especially in the long bones (upper arms and thighs). The rate at which cartilage cells in the growth plates of the long bones turn into bone is slow, leading to short bones and reduced height.

Symptoms:

Disproportionate short stature
double jointedness, caused by lax (loose) ligaments in some joints
Large head and short arms and legs
increased curvature of the lower back (sway back) making the buttocks appear more prominent (lordosis).
increased curvature of upper back making back appear slightly hunched (kyphosis)
middle ear infections, which can result in hearing loss
reduced muscle tone
waddling gait, bowed legs
Limited twisting ability available at the elbows.
Hands are short. Feet are short, flat, and broad.
intelligence is generally normal.
Affected men average 51.8 inches in height, while women average 48.6 inches
Abnormal hand appearance (trident hand) with persistent space between the long and ring finger

narrowed foramen magnums which can compress the brain stem and spinal cord. Symptoms of narrowing include apnea (cessation of breathing) and cervical myelopathy

flat or depressed area at the base of the nose
 
protruding jaw and sometimes poor dental structure (The teeth are crowded and the upper and lower teeth may be poorly aligned.)

 INHERITANCE:

The type of inheritance of achondroplasia is an autosomal dominant genetic disorder. The disorder is caused by a defect in the fibroblast growth factor receptor-3 protein (FGFR-3), which is located on chromsome 4, gene map locus 4p16.3. The frequency of this disorder varies from 1 in 10000 to 1 in 40000.  A couple with one spouse being achondroplastic, will have a 50% chance of generating an offspring without this disorder and a 50% probability of producing a child with achondroplasia. When both parents have this disorder they have a 25% chance of producing a child without achondroplasia., a 50% chance of getting a child with achondroplasia and a 25% chance of producing an offspring who has two copies of this mutated gene which makes it homozygous for this trait. This “double dominance” is fatal to the baby, because it won’t be able to convert any cartilage into bone, and due to this the chance to survive beyond age 1 is highly doubtful. Couples in which neither spouse has the disorder have a slight chance of producing a child with this genetic defect, because of the mutation. In 80% of the cases it is not inherited but caused by a point mutation in the FGFR-3 gene. The likelihood of producing a child with this defect is greater as the father gets older. It is one of the few genetic diseases in which the frequency increases as the father ages. Usually they are maternally related.
 

GENETIC TESTS
Amniocentesis,

CHROMOSOME ABNORMALITIES

The problem with achondroplasia is the defect on chromosome 4, mapping locus 4p16.3. A mutation of the fibroblast growth factor – 3 gene is the main cause for this disorder. Two groups of investigators have recently reported analyses of the FGFR3 gene in people with achondroplasia. Shiang and his team of scientists, as well as Rousseau and his colleagues discovered that a mutation found on the FGFR3 gene was unique to individuals with achondroplasia. No such mutation was found in the DNA from unaffected persons. In families with multiple affected members the identified mutations were inherited with the disorder. Amazingly, both groups found that every mutation was at exactly the same nucleotide in the transmembrane domain of the FGFR3 gene. In all but a very few other genetic disorders studied thus far, different affected families have different mutations in the disease gene. Shiang et al. found that 15 of the 16 achondroplasia mutations they analyzed had a guanine-to-adenine (G-to-A) transition at nucleotide 1138; the 16th mutation was a guanine-to-cytosine (G-to-C) transversion at the same nucleotide.  Both mutations resulted in the substitution of arginine for glycine at amino acid 380 of the protein. Similarly, Rousseau et al. found that all 23 achondroplasia mutations in their series resulted in the same substitution at the same amino acid of the transmembrane domain of the FGFR3 protein. This high proportion of identical mutations (100 percent for the amino acid change), which is unprecedented for an autosomal dominant disorder in which more than 80 percent of cases represent new mutations, may explain the consistency of the phenotype in achondroplasia

TREATMENTS

Unfortunately no treatments are available for achondroplasia as a disease itself.  However, there are possible treatments for the symptoms.  Although controversial, lengthening is a possibility to help increase the height for children with achondroplasia.  Lengthening has to occur between the ages of 6-10 for the first treatment and can spur growth between 30-35 cm on the lower limb and 10-12 cm on the upper limb.  Duration of this treatment approximately 5 months.  There are also can be treatments for leg and knee deformities as well as tightening the ligaments in the arms and legs.  This stage should be done between the ages of 12 and 14 and duration for this procedure is approximately 8-10 months.

WHERE CAN I FIND MORE INFORMATION?

Human Growth Foundation
7777 Leesburg Pike,
Suite 202 South,
Falls Church, VA 22043,
telephone (800) 451-6434.
Website: http://www.hgfound.org

Little People of America (LPA)
Box 9897, Washington, DC 20016.
Website: http://www.lpaonline.org

Maryland Center for Limb Lengthening and Reconstruction
22 S. Greene Street
Baltimore, MD 21201
(410) 448-6780

http://www.umm.edu/mcllr/mcllr_achond.htm?source=goto
March of Dimes
1-888-MODIMES
www.modimes.org

REFERENCES
Yahoo Health
http://health.yahoo.com/health/dc/001577/0.html