Osteogenesis imperfecta

Genetic bone disorder (brittle bone disease) caused by a variety of gene defects (most commonly COL1A1 and COL1A2). Most common form is autosomal dominant with ↓ production of otherwise normal type I collagen (altered triple helix formation).

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Manifestations include:

• Multiple fractures and bone deformities (arrows in A) after minimal trauma (eg, during birth)
• Blue sclerae B due to the translucent connective tissue over choroidal veins
• Some forms have tooth abnormalities, including opalescent teeth that wear easily due to lack of dentin (dentinogenesis imperfecta)
• Conductive hearing loss (abnormal ossicles)

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Osteogenesis Imperfecta: Management

May be confused with child abuse. Treat with bisphosphonates to ↓ fracture risk. Patients can’t BITE.

• Bones = multiple fractures
• I (eye) = blue sclerae
• Teeth = dental imperfections
• Ear = hearing loss

Ehlers-Danlos syndrome

Faulty collagen synthesis causing hyperextensible skin A, hypermobile joints B, and tendency to bleed (easy bruising). Multiple types. Inheritance and severity vary. Can be autosomal dominant or recessive. May be associated with joint dislocation, berry and aortic aneurysms, organ rupture.

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Ehlers-Danlos Syndrome: Types

Hyper-mobility type (joint instability): most common type.

Classical type (joint and skin symptoms): caused by a mutation in type V collagen (eg, COL5A1, COL5A2).

Vascular type (fragile tissues including vessels [eg, aorta], muscles, and organs that are prone to rupture [eg, gravid uterus]): mutations in type III procollagen (eg, COL3A1).

Menkes disease

X-linked recessive connective tissue disease caused by impaired copper absorption and transport due to defective Menkes protein ATP7A (Absent copper), vs ATP7B in Wilson disease (copper Buildup). Leads to ↓ activity of lysyl oxidase (copper is a necessary cofactor) ⇒ defective collagen cross-linking. Results in brittle, “kinky” hair, growth and developmental delay, hypotonia, ↑ risk of cerebral aneurysms.

Topics Covered:

• Osteogenesis Imperfecta: Genetic Basis
• Osteogenesis Imperfecta: Clinical Features
• Osteogenesis Imperfecta: Differential and Treatment
• Ehlers-Danlos Syndrome: Overview
• Ehlers-Danlos Syndrome: Specific Types
• Menkes Disease