Gnathodiaphyseal dysplasia

On this page:

What is gnathodiaphyseal dysplasia?

Gnathodiaphyseal dysplasia is a disorder that affects the bones. People with this condition have reduced bone mineral density (osteopenia), which causes the bones to be unusually fragile. As a result, affected individuals typically experience multiple bone fractures in childhood, often from mild trauma or with no apparent cause.

While most bone tissue is less dense than normal in gnathodiaphyseal dysplasia, the outer layer (cortex) of the shafts of the long bones in the arms and legs is abnormally hard and thick (diaphyseal sclerosis). Bowing of the long bones also occurs in this disorder.

Jaw problems are common in gnathodiaphyseal dysplasia; the prefix "gnatho-" in the condition name refers to the jaw. Affected individuals may develop bone infections (osteomyelitis) in the jaw, which can lead to pain, swelling, discharge of pus from the gums, loose teeth, and slow healing after teeth are lost or extracted. Areas of the jawbone may lose the protective coverage of the gums, which can result in deterioration of the exposed bone (osteonecrosis of the jaw). Also, normal bone in areas of the jaw may be replaced by fibrous tissue and a hard material called cementum, which normally surrounds the roots of teeth and anchors them in the jaw. These areas of abnormal bone, called cementoosseous lesions, may be present at birth or develop later in life.

When gnathodiaphyseal dysplasia was first described, it was thought to be a variation of another bone disorder called osteogenesis imperfecta, which is also characterized by frequent bone fractures. However, gnathodiaphyseal dysplasia is now generally considered to be a separate condition. Unlike in osteogenesis imperfecta, the fractures in gnathodiaphyseal dysplasia heal normally without causing deformity or loss of height.

Read more about osteogenesis imperfecta.

How common is gnathodiaphyseal dysplasia?

The prevalence of gnathodiaphyseal dysplasia is unknown, but it is thought to be a rare disorder. A few affected individuals and families have been described in the medical literature.

What genes are related to gnathodiaphyseal dysplasia?

Gnathodiaphyseal dysplasia is caused by mutations in the ANO5 gene, which provides instructions for making a protein called anoctamin-5. While the specific function of this protein is not well understood, it belongs to a family of proteins, called anoctamins, that act as chloride channels. Studies suggest that most anoctamin channels are turned on (activated) in the presence of positively charged calcium atoms (calcium ions); these channels are known as calcium-activated chloride channels. The mechanism for this calcium activation is unclear.

The ANO5 gene mutations that have been identified in people with gnathodiaphyseal dysplasia change single protein building blocks (amino acids) in the anoctamin-5 protein. It is unclear how these protein changes lead to the fragile bones, jaw problems, and other skeletal abnormalities that occur in gnathodiaphyseal dysplasia. Researchers suggest that the mutations may affect the way cells process calcium, an important mineral in bone development and growth.

How do people inherit gnathodiaphyseal dysplasia?

This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder.

Where can I find information about diagnosis or management of gnathodiaphyseal dysplasia?

These resources address the diagnosis or management of gnathodiaphyseal dysplasia and may include treatment providers.

You might also find information on the diagnosis or management of gnathodiaphyseal dysplasia inEducational resources and Patient support.

General information about the diagnosis and management of genetic conditions is available in the Handbook.

To locate a healthcare provider, see How can I find a genetics professional in my area? in the Handbook.

Where can I find additional information about gnathodiaphyseal dysplasia?

You may find the following resources about gnathodiaphyseal dysplasia helpful. These materials are written for the general public.

MedlinePlus - Health information (5 links)
Additional NIH Resources - National Institutes of Health (2 links)
Educational resources - Information pages (4 links)
Patient support - For patients and families
Children's Craniofacial Association

You may also be interested in these resources, which are designed for healthcare professionals and researchers.

PubMed - Recent literature
OMIM - Genetic disorder catalog

What other names do people use for gnathodiaphyseal dysplasia?

GDD
gnathodiaphyseal sclerosis
Levin syndrome 2
osteogenesis imperfecta, Levin type
osteogenesis imperfecta with unusual skeletal lesions

For more information about naming genetic conditions, see the Genetics Home Reference Condition Naming Guidelines and How are genetic conditions and genes named? in the Handbook.

What if I still have specific questions about gnathodiaphyseal dysplasia?

Ask the Genetic and Rare Diseases Information Center

Where can I find general information about genetic conditions?

The Handbook provides basic information about genetics in clear language.

These links provide additional genetics resources that may be useful.

What glossary definitions help with understanding gnathodiaphyseal dysplasia?

acids ; autosomal ; autosomal dominant ; bone mineral density ; calcium ; cell ; cementum ; chloride ;chloride channels ; dysplasia ; gene ; gums ; inherited ; ions ; mineral ; osteogenesis ; osteomyelitis ;osteopenia ; prevalence ; protein ; sclerosis ; syndrome ; tissue ; trauma

You may find definitions for these and many other terms in the Genetics Home Reference Glossary.

References (5 links)

The resources on this site should not be used as a substitute for professional medical care or advice. Users seeking information about a personal genetic disease, syndrome, or condition should consult with a qualified healthcare professional. See How can I find a genetics professional in my area? in the Handbook.