Brittle Cornea Syndrome (BCS)

ESTIMATED PREVALENCE: <1 in 1,000,000 [52]

INHERITANCE PATTERN: Autosomal Recessive

SYMPTOMS:

Brittle Cornea Syndrome (BCS) affects the eyes, but can also involve the ears, joints, and skin. Characteristics of the eyes include thinning, fragility, protrusion, perforation and/or rupture of the cornea after no/minimal trauma, the presence of blue sclera, and nearsightedness. Patients may also present with deafness, skin and skeletal manifestations, due to mutations in the soft tissue.

DIAGNOSTIC CRITERIA [53]:

To diagnose BCS, the following formula must be satisfied:

Major Criterion #1 + one other Major Criterion, OR three (3) Minor Criteria

To diagnose BCS, a patient must have Major Criterion #1 (thin cornea, with or without rupture (central corneal thickness, often <400 µm), plus one other Major Criterion or three (3) Minor Criteria. Patients may also undergo molecular testing on two gene variants involved with respect to either ZNF469 or PRDM5. However, some patients possess neither gene variant, so genetic testing isn’t required for a diagnosis.

Major Diagnostic Criteria

  • Thin cornea, with or without rupture (central corneal thickness often <400 µm)
  • Early-onset progressive keratoconus
  • Early-onset progressive keratoglobus
  • Blue sclerae

Minor Diagnostic Criteria

  • Enucleation or corneal scarring as a result of previous rupture
  • Progressive loss of corneal stromal depth, especially in central cornea
  • High myopia, with normal or moderately increased axial length
  • Retinal detachment
  • Deafness, often with mixed conductive and sensorineural components, progressive, higher frequencies often more severely affected (“sloping” pure tone audiogram),
  • Hypercompliant tympanic membranes
  • Developmental dysplasia of the hip
  • Hypotonia in infancy, usually mild if present
  • Scoliosis
  • Arachnodactyly
  • Hypermobility of distal joints
  • Pes planus, hallux valgus
  • Mild contractures of fingers (especially 5th)
  • Soft, velvety skin, translucent skin

Genetic Markers:

ZNF469

PRDM5