Growth disorder: Skeletal dysplasia Flashcards
Define skeletal dysplasia.
The skeletal dysplasias (osteochondrodysplasias) are a heterogeneous group of more than 350 disorders frequently associated with orthopedic complications and varying degrees of dwarfism or short stature. These disorders are diagnosed based on radiographic, clinical, and molecular criteria.
Define achondroplasia.
Achondroplasia is a genetic disorder that results in dwarfism. In those with the condition, the arms and legs are short, while the torso is typically of normal length.
Define hypochondroplasia.
Hypochondroplasia (HCH) is a developmental disorder caused by an autosomal dominant genetic defect in the fibroblast growth factor receptor 3 gene (FGFR3) that results in a disproportionately short stature, micromelia (small extremities) and a head that appears large in comparison with the underdeveloped portions of the body. It is essentially a less severe form of achondroplasia, which can become evident only later in childhood.
Define osteogenesis imperfecta.
Osteogenesis imperfecta (OI), also known as brittle bone disease, is a group of genetic disorders that mainly affect the bonesIt results in bones that break easily. The severity may be mild to severe. Other symptoms may include a blue tinge to the whites of the eye, short height, loose joints, hearing loss, breathing problems and problems with the teeth.
What are the nine types of osteogenesis imperfecta?
Type I: Mild
Type II: Severe and usually lethal in the perinatal period
Type III: Considered progressive and deforming
Type IV: Deforming, but with normal sclerae most of the time
Type V: Shares the same clinical features of IV, but has unique histological findings (“mesh-like”)
Type VI: Shares the same clinical features of IV, but has unique histological findings (“fish scale”)
Type VII: Associated with cartilage associated protein
Type VIII: Severe to lethal, associated with the protein leprecan
Type IX: Lethal
Explain the aetiology/risk factors for achondroplasia.
AD. Achondroplasia is caused by a mutation in fibroblast growth factor receptor 3 (FGFR3) gene. In normal development 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.
Explain the aetiology/risk factors for hypochondroplasia.
AD. Also caused by FGFR3 mutation.
Explain the aetiology/risk factors for osteogenesis imperfecta.
People with OI are born with defective connective tissue, or without the ability to make it, usually because of a deficiency of Type-I collagen. This deficiency arises from an amino acid substitution of glycine to bulkier amino acids in the collagen triple helix structure. The larger amino acid side-chains create steric hindrance that creates a bulge in the collagen complex, which in turn influences both the molecular nanomechanics and the interaction between molecules, which are both compromised. As a result, the body may respond by hydrolyzing the improper collagen structure. If the body does not destroy the improper collagen, the relationship between the collagen fibrils and hydroxyapatite crystals to form bone is altered, causing brittleness.
As a genetic disorder, OI has historically been viewed as an autosomal dominant disorder of type I collagen. Most cases have been caused by mutations in the COL1A1and COL1A2 genes. In the past several years, there has been the identification of autosomal recessive forms. Most people with OI receive it from a parent but in 35% of cases it is an individual (de novo or “sporadic”) mutation.
Summarise the epidemiology of skeletal dysplasia.
Rare
What are the presenting signs and symptoms of achondroplasia (and hypochondroplasia?
Shortened long bones > Dwarfism
- Disproportionate short stature
- Rhizomelic (proximal) shortening
- Short metacarpals
- Short phalanges (brachydactyly)
- Trident hand - tips of giners can’t touch
- Varus legs
Flat bone defects
- Large head size
- Frontal bossing
- Flattened nasal bridge
- Narrow foramen magnum
- Spinal lordosis
What are the presenting signs and symptoms of osteogenesis imperfecta?
Depends on subtype a lot but generally - blue tinge to the whites of the eye, short height, loose joints, hearing loss, breathing problems and problems with the teeth.
What are appropriate investigations for skeletal dysplasia?
Radiology & Karyotyping
What is the management for skeletal dysplasia?
No cure.
What is the management for achondroplasia/hypochondroplasia?
- GH will not help
- Limb lengthening surgery in early years may help
- Physical therapy
- Physical aids
- Genetic counselling
What is the management for osteogenesis imperfecta?
- Bisphosphonates in children
- Orthopaedic surgery with long metal rods being put through bones to make them stronger
- Physical therapy
- Physical aids
- Genetic counselling
