Conditions · Metabolism (biochemistry)
Osteogenesis imperfecta !
An inherited type I collagen disorder that makes bones fragile: they break with minimal force; blue sclerae and deafness are common.
Updated 2026-11-01
Structures involved
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In biochemistry
In histology
- Connective tissue proper: cells and fibres
- Bone tissue: cells, compact and spongy bone
- Extracellular matrix: collagen types, elastin, ground substance
In embryology
Why it happens
What it is
A group of inherited connective-tissue disorders, nearly always from COL1A1 or COL1A2 variants, with bone fragility and repeated fractures (“brittle bone disease”).
Who gets it
Affects about 1 in 10,000 to 20,000 people worldwide. No Colombia-specific data were found; care is given in genetics and paediatric orthopaedic services.
Causes
- COL1A1 or COL1A2 variants (≈ 90 % of cases), autosomal dominant; many are new (no family history)
- Rare recessive forms from genes that modify or fold collagen (CRTAP, P3H1, PPIB, SERPINF1 and others)
Risk factors
- An affected parent (50 % chance of inheriting it in dominant forms)
- Germline mosaicism in healthy parents (explains some affected siblings)
Pathophysiology
Type I collagen is a trimer of two α1 and one α2 chains. If a variant lowers the number of normal chains (null allele), half the usual amount of good-quality collagen is made: a mild form (type I). If it changes a glycine of the Gly–X–Y repeat, the abnormal chain enters the trimers and spoils them (dominant-negative effect): the triple helix folds late, is over-modified and degraded, giving severe forms (II, III, IV). Bone ends up with little matrix and disordered mineralisation; dentine, sclera (thin, showing the blue choroid) and the ear ossicles are also affected.
Classification
- Type I: mild, non-deforming, blue sclerae, deafness in adulthood
- Type II: lethal in the perinatal period, fractures in utero
- Type III: progressively deforming, very short stature
- Type IV: moderate, normal or grey sclerae
Symptoms and signs
- Fractures from minimal trauma, especially in childhood
- Blue or grey sclerae
- Hearing loss from adolescence or adulthood
- Dentinogenesis imperfecta (opalescent, fragile teeth)
- Short stature, bowing of long bones and scoliosis
- Ligament laxity and thin skin
Diagnosis
- Clinical
- Fractures from minimal trauma plus blue sclerae, dentinogenesis imperfecta, deafness or a family history.
- Tests
- Genetic testing of COL1A1, COL1A2 and recessive genes; calcium, phosphate, alkaline phosphatase and vitamin D to rule out other causes; audiometry.
- Imaging
- X-rays: osteopenia, fractures at different stages, thin bowed long bones and Wormian bones in the skull; bone densitometry (DXA); prenatal ultrasound in severe forms.
Treatment
- Medical
- Bisphosphonates to raise bone density and reduce fractures, especially in children with moderate or severe forms
- Surgical
- Intramedullary rods (including telescopic rods that grow with the child) to correct deformity and prevent fractures
- Rehabilitation
- Physiotherapy, hydrotherapy and mobility aids that build strength without stressing bone
- Procedure
- Hearing aids or stapes surgery when hearing is lost
- Follow-up
- Follow-up of spine, hearing, teeth and breathing
Complications
- Deformity and motor disability
- Scoliosis and respiratory failure
- Deafness
- Basilar invagination
Prognosis
Highly variable: type I has a near-normal life expectancy; type II is usually fatal at birth; in type III respiratory failure is the main cause of death.
Prevention
- Genetic counselling and prenatal diagnosis in affected families
Test yourself
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Which genes cause most cases of osteogenesis imperfecta?
COL1A1 and COL1A2, which encode the chains of type I collagen (≈ 90 % of cases).
Why does a glycine change in collagen cause a severe form?
Glycine is the only residue that fits the centre of the triple helix; the abnormal chain enters the trimers and damages them (dominant-negative effect).
Why do the sclerae look blue?
The collagen-poor sclera is thin and lets the colour of the underlying choroid show through.
What must multiple fractures in an infant with osteogenesis imperfecta be distinguished from?
Child abuse; sclerae, teeth, family history, X-rays and genetic testing help.
Related conditions
Educational information, not medical advice. For any symptom, see a health professional.
Sources: Osteogenesis imperfecta: MedlinePlus Genetics (MedlinePlus, US National Library of Medicine, 2026); Osteogenesis imperfecta: MedlinePlus Medical Encyclopedia (MedlinePlus, US National Library of Medicine, 2026); COL1A1 gene: MedlinePlus Genetics (MedlinePlus, US National Library of Medicine, 2026); COL1A2 gene: MedlinePlus Genetics (MedlinePlus, US National Library of Medicine, 2026).
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