Congenital Fibre-Type Disproportion (CFTD) is a rare congenital myopathy characterized by a disproportion in muscle fibre size. The key features and considerations for CFTD are summarized below:

Overview

CFTD is considered a diagnosis of exclusion. It is defined by:

1. Histological Findings: A significant reduction in the size of type 1 (slow-twitch) muscle fibres relative to type 2 (fast-twitch) fibres. The size difference should be at least 35–40%, with no other major histological abnormalities present.
2. Clinical Features: Symptoms resemble those seen in other congenital myopathies, including generalized muscle weakness and hypotonia.

Associated Conditions

Fibre-size disproportion can occur as a secondary phenomenon in a range of conditions, including:

• Central Nervous System (CNS) Disorders
• Peripheral Neuropathies
• Muscular Dystrophies
• Other congenital myopathies such as:
  • Nemaline Myopathy
  • Multiminicore Disease
  • Centronuclear Myopathy

CFTD is distinguished by the absence of other defining features of these conditions and by the predominance of fibre-type disproportion as the sole significant histological abnormality.

Genetics and Inheritance

CFTD exhibits genetic heterogeneity, with both autosomal dominant and recessive inheritance patterns. Some cases involve de novo dominant mutations.

Genes Associated with CFTD:

1. Dominant Mutations:

   • ACTA1 (Skeletal α-actin)
   • TPM3 (α-TropomyosinSLOW)
   • TPM2 (β-Tropomyosin)

2. Recessive Mutations:

   • SEPN1 (Selenoprotein N)
   • RYR1 (Ryanodine Receptor)

Overlap with Other Myopathies:

The same genetic mutations are often associated with nemaline myopathy, indicating a shared pathogenic mechanism.

Clinical Presentation

The clinical phenotype of CFTD varies widely depending on the underlying genetic mutation. Features may include:

• Congenital hypotonia
• Delayed motor milestones
• Muscle weakness (generalized or proximal)
• Respiratory involvement in severe cases