Dwarfism
Kevin October 29th, 2007
Both Amy and Zach have a condition called Achondroplasia Dwarfism. Matt, however, has a different type called Diastrophic Dysplasia. Below is a brief FAQ for each type of dwarfism to help you learn more about the conditions affecting the Roloffs.
Achondroplasia Dwarfism (Amy & Zach):
What does the name mean?
Achondroplasia literally means failure or lack of cartilage formation. This is not strictly true as cartilage formation does occur in the growth plates of patients with achondroplasia.
How common is achondroplasia?
Achondroplasia is the most common skeletal dysplasia. Although the exact incidence is not known estimates range from 1 in 15,000 to 1 in 26,000 births.
Is achondroplasia inherited?
Achondroplasia is inherited in an autosomal dominant manner, but about 75% of patients with achondroplasia represent new mutations. These new mutations are typically arise from the father during sperm formation. Paternal age greater than 35 years has been found to be a risk factor.
What causes achondroplasia?
Achondroplasia is caused by a mutation in the fibroblast growth factor receptor-3 (FGFR-3) gene. Mutations which change the amino acid glycine to arginine at position 380 of the FGFR-3 protein account for >97% of all reported cases of achondroplasia. Normally the FGFR-3 protein functions as “brake” for endochondral bone growth. This typical G380R mutation actually increases the ability of the FGFR-3 protein to slow bone growth and causes the features of achondroplasia. This type of change associated with an increased ability is termed a “gain-of-function” mutation.
Diastrophic Dysplasia (Matt):
What does the name mean?
The term ‘diastrophic’ is Greek and means ‘crooked’.
How common is diastrophic dysplasia?
Although diastrophic dysplasia occurs in most countries, the highest prevalence is found in Finland (1 in 33,000) where the carrier rate in the population is 1 – 2%. The incidence in non-Finnish populations is considerably lower, being 1 in 500,000 live births.
Is diastrophic dysplasia inherited?
Diastrophic dysplasia is inherited as an autosomal recessive trait, with very wide variability of phenotypic expression. Approximately 5% of cases constitute new mutations.
What causes diastrophic dysplasia?
Diastrophic dysplasia is caused by a mutation in the gene coding for a sulfate transporter protein that is essential for normal cartilage function. This protein is called DTDST and was first identified by Hastabacka and colleagues in 1994. The gene is located on chromosome 5 (5q31-q34). Mutations in the same gene are responsible for lethal chondrodysplasias.
Proteoglycans are complex molecules that absorb water and facilitate load bearing in articular cartilage. Reduction in sulfate transporter concentrations in chondrocytes causes under-sulfation of the proteoglycan matrix and predisposes individuals to early degenerative joint disease. Diastrophic dysplasia affects chondrocyte function in the growth plate, epiphyseal region and other areas such as the trachea.
[Source: Nemours.org - Diastrophic and Achondroplasia]