Osteoglophonic dysplasia

Alternate names

• Fairbank-Keats syndrome
• OGD
• osteoglophonic dwarfism

Definition

Osteoglophonic dysplasia is a condition characterized by abnormal bone growth that leads to severe head and face (craniofacial) abnormalities, dwarfism, and other features. The term osteoglophonic refers to the bones (osteo-) having distinctive hollowed out (-glophonic) areas that appear as holes on x-ray images.

Epidemiology

Osteoglophonic dysplasia is a rare disorder; its prevalence is unknown. Only about 15 cases have been reported in the medical literature.

Cause

• Osteoglophonic dysplasia is caused by mutations in the FGFR1 gene, which provides instructions for making a protein called fibroblast growth factor receptor 1.
• This protein is one of four fibroblast growth factor receptors, which are related proteins that bind (attach) to other proteins called fibroblast growth factors.
• The growth factors and their receptors are involved in important processes such as cell division, regulation of cell growth and maturation, formation of blood vessels, wound healing, and embryonic development.
• In particular, they play a major role in skeletal development.
• The FGFR1 protein spans the cell membrane, so that one end of the protein remains inside the cell and the other end projects from the outer surface of the cell.
• When a fibroblast growth factor binds to the part of the FGFR1 protein outside the cell, the receptor triggers a cascade of chemical reactions inside the cell that instruct the cell to undergo certain changes, such as maturing to take on specialized functions.
• The FGFR1 protein is thought to play an important role in the development of the nervous system.
• This protein may also help regulate the growth of long bones, such as the large bones in the arms and legs.

Gene mutations

• FGFR1 gene mutations that cause osteoglophonic dysplasia change single building blocks (amino acids) in the FGFR1 protein.
• The altered FGFR1 protein appears to cause prolonged signaling, which promotes premature fusion of bones in the skull and disrupts the regulation of bone growth in the arms and legs.

Inheritance

Autosomal dominant pattern, a 50/50 chance.

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. Most cases result from new mutations in the gene and occur in people with no history of the disorder in their family. However, some affected individuals inherit the mutation from an affected parent.

Signs and symptoms

• Premature fusion of certain bones in the skull (craniosynostosis) typically occurs in osteoglophonic dysplasia.
• The craniosynostosis associated with this disorder may give the head a tall appearance, often referred to in the medical literature as a tower-shaped skull, or a relatively mild version of a deformity called a cloverleaf skull.
• Characteristic facial features in people with osteoglophonic dysplasia include a prominent forehead (frontal bossing), widely spaced eyes (hypertelorism), flattening of the bridge of the nose and of the middle of the face (midface hypoplasia), a large tongue (macroglossia), a protruding jaw (prognathism), and a short neck.
• People with this condition usually have no visible teeth because the teeth never emerge from the jaw (clinical anodontia).
• In addition, the gums are often overgrown (hypertrophic gingiva).
• Infants with osteoglophonic dysplasia often experience failure to thrive, which means they do not gain weight and grow at the expected rate.
• Affected individuals have short, bowed legs and arms and are short in stature.
• They also have flat feet and short, broad hands and fingers.

Clinical presentation

For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed.

80%-99% of people have these symptoms

• Abnormal form of the vertebral bodies
• Craniosynostosis
• Hypertelorism(Wide-set eyes)
• Multiple unerupted teeth(Multiple non-erupting teeth)
• Reduced number of teeth(Decreased tooth count)
• Severe short stature(Dwarfism)

30%-79% of people have these symptoms

• Abnormal clavicle morphology(Abnormal collarbone)
• Anteverted nares(Nasal tip, upturned)
• Delayed skeletal maturation(Delayed bone maturation)
• Failure to thrive in infancy(Faltering weight in infancy)
• Micrognathia(Little lower jaw)
• Protruding ear(Prominent ear)
• Rhizomelia(Disproportionately short upper portion of limb)

5%-29% of people have these symptoms

• Abnormal bone ossification
• Brachydactyly(Short fingers or toes)
• Choanal atresia(Blockage of the rear opening of the nasal cavity)
• Cryptorchidism(Undescended testes)
• Inguinal hernia
• Intellectual disability(Mental deficiency)
• Scoliosis

NIH genetic and rare disease info

• NIH info on Osteoglophonic dysplasia

Osteoglophonic dysplasia is a rare disease.

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