Congenital Anomalies and Achondroplasia

Congenital Anomalies

• Congenital anomalies result from localized abnormalities in mesenchyme migration and condensation (dysostosis) or global disorganization of bone and/or cartilage (dysplasia).

Achondroplasia

• Achondroplasia is an autosomal dominant disorder caused by retarded cartilage growth due to gain-of-function mutations in fibroblast growth factor receptor 3 (FGFR3).
• It is the most common skeletal dysplasia and a major cause of dwarfism.
• Affected individuals have shortened proximal extremities, a trunk of relatively normal length, and an enlarged head with specific facial features.

Type I Collagen Diseases (Osteogenesis Imperfecta)

• Osteogenesis Imperfecta is the most common inherited disorder of connective tissue caused by deficiencies in the synthesis of type I collagen.
• It principally affects bone and other tissues rich in type I collagen.
• The inheritance pattern is autosomal dominant.
• The fundamental abnormality is too little bone, leading to extreme skeletal fragility.

Osteogenesis Imperfecta - Other Findings

• Blue sclerae are due to decreased collagen content.
• Hearing loss is related to sensorineural deficit and impeded conduction.
• Dental imperfections include small, misshapen, and blue-yellow teeth due to dentin deficiency.

Osteopetrosis

• Osteopetrosis is also known as marble bone disease, characterized by reduced bone resorption and skeletal sclerosis.
• Bones are abnormally brittle and fracture easily.
• The condition is classified into variants based on inheritance and clinical severity.

Osteopetrosis - Genetic Mutations

• Genetic mutations interfere with acidification of osteoclast resorption pit.
• Bones lack medullary canal, with bulbous and misshapen long bone ends.

Osteopetrosis - Clinical Features

• Small neural foramina compress exiting nerves.
• Primary spongiosa persists, filling medullary cavity.
• Severe infantile osteopetrosis is often fatal due to leukopenia despite extramedullary hematopoiesis.

Osteopetrosis - Mild Form

• Mild autosomal dominant form may not be detected until adolescence or adulthood.
• It is often discovered on radiographic studies for repeated fractures.
• Individuals may have mild cranial nerve deficits and anemia.