Genetics · MU Sofia

23. Hereditary Connective Tissue and Bone System Diseases: Osteogenesis Imperfecta (OI)

Covers osteogenesis imperfecta, the brittle bone disease caused mainly by mutations in the COL1A1 and COL1A2 genes that affect type I collagen. It moves from the molecular basis and pathogenesis to the Sillence classification of types I to IV, then clinical features, diagnosis, management and prognosis. The note also includes a clinical relevance section on distinguishing the condition from child abuse.

Inside: 9 sections · 4 labelled pictures · 15 flashcards · 3 min

Topic 23 of 65 in the MU Sofia syllabus for Genetics (Medicine, Year 3). The free AceMed note covers it in 9 sections, about 472 words (3 min of reading), with 15 flashcards.

In this note

  1. Hereditary Connective Tissue and Bone System Diseases: Osteogenesis Imperfecta (OI)
  2. I. Introduction
  3. II. Molecular Basis
  4. III. Classification (Sillence Classification – major types)
  5. IV. Clinical Features
  6. V. Diagnosis
  7. VI. Management
  8. VII. Prognosis
  9. VIII. Clinical Relevance

I. Introduction

Osteogenesis imperfecta (OI), also known as “brittle bone disease”, is a group of genetic connective tissue disorders characterized by:

  • Bone fragility and multiple fractures,
  • Defective connective tissue (due to abnormal collagen type I),
  • Extraskeletal features (hearing loss, dentinogenesis imperfecta, blue sclerae).

It is one of the most common inherited bone disorders.

II. Molecular Basis

  • Defective synthesis of type I collagen (major structural protein in bone, dentin, sclera, ligaments).
  • Mutations most commonly in COL1A1 and COL1A2 genes → abnormal α chains of collagen type I.
  • Inheritance: mostly autosomal dominant, but recessive and de novo cases also reported.

Pathogenesis

  • Collagen is quantitatively reduced or structurally abnormal.
  • Results in weak bone matrix, reduced tensile strength, and systemic connective tissue fragility.

III. Classification (Sillence Classification – major types)

  1. 1. Type I (Mild)
  • Most common and mildest form.
  • Normal stature, fractures during childhood (↓ after puberty).
  • Blue sclerae (due to thinning of sclera, underlying choroid visible).
  • Hearing loss (otosclerosis of middle ear bones).
  • Normal life expectancy.
  1. 2. Type II (Perinatal lethal)
  • Most severe form, usually lethal in utero or shortly after birth.
  • Multiple fractures, skeletal deformities.
  • Extremely fragile bones, underdeveloped lungs.
  1. 3. Type III (Severe, progressively deforming)
  • Severe bone fragility, frequent fractures, progressive deformities.
  • Short stature, kyphoscoliosis, barrel-shaped chest.
  • Normal sclera (sometimes blue at birth → white with age).
  • Wheelchair-dependent, reduced life expectancy.
  1. 4. Type IV (Moderate severity)
  • Variable severity between Type I and III.
  • Fractures, mild to moderate bone deformity.
  • Normal sclerae.
  • May have dentinogenesis imperfecta.

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