Cameron (1993) described 11 patients with blue sclerae, limbus-to-limbus corneal thinning, hypermobile joints, and consanguineous parents. Corneal rupture occurred in 7 patients (9 eyes) either spontaneously or following minimal trauma. Acute hydrops occurred in 3 patients. Bilateral microcornea ... Cameron (1993) described 11 patients with blue sclerae, limbus-to-limbus corneal thinning, hypermobile joints, and consanguineous parents. Corneal rupture occurred in 7 patients (9 eyes) either spontaneously or following minimal trauma. Acute hydrops occurred in 3 patients. Bilateral microcornea was present in 1 patient, and 2 patients had unilateral increased corneal diameter due to secondary glaucoma after trauma. Peripheral sclerocornea was present bilaterally in 5 patients. Curvature abnormalities included cornea plana, keratoconus, and keratoglobus. Systemic abnormalities included increased skin laxity, pectus excavatum, scoliosis, congenital hip dislocation, recurrent shoulder dislocation, high-frequency hearing loss, high-arched palate, and mitral valve prolapse. Cameron (1993) stated that the term 'blue sclera' in this syndrome is a misnomer, as the sclera is more transparent and thinner than normal, revealing underlying uveal tissue; the blue appearance is most apparent in the region of the ciliary body, giving the appearance of a 'halo' at the limbus. In addition, photographic comparisons in patients followed for more than 5 years showed a less prominent blue appearance of the sclera with increasing age. Burkitt Wright et al. (2011) reported a large consanguineous Pakistani family (designated 'BC-001') in which 4 sisters had corneal rupture after minor trauma. The affected sisters had high myopia, blue sclerae, keratoconus, keratoglobus, soft skin with easy bruising, hypermobility of the small joints, femoral epiphyseal changes, abnormal gait, hypercompliance of tympanic membranes, and mixed conductive and sensorineural deafness. Burkitt Wright et al. (2011) identified a second consanguineous Pakistani family ('BC-002') in which affected individuals had thin corneas, blue sclerae, mixed sensorineural/conductive deafness with hypercompliant tympanic membranes, and small joint hypermobility. Patients from both families had normal lysylpyridinoline/hydroxylysylpyridinoline urinary excretion ratios, thus excluding Ehlers-Danlos syndrome type VI (225400).
In affected members of a consanguineous Pakistani family (BC-001) with brittle cornea syndrome mapping to chromosome 4, Burkitt Wright et al. (2011) identified a 52.46-kb homozygous deletion involving exons 9 to 14 of the PRDM5 gene (614161.0001). Heterozygous ... In affected members of a consanguineous Pakistani family (BC-001) with brittle cornea syndrome mapping to chromosome 4, Burkitt Wright et al. (2011) identified a 52.46-kb homozygous deletion involving exons 9 to 14 of the PRDM5 gene (614161.0001). Heterozygous carriers of the deletion had blue sclerae, small joint hypermobility, and central corneal thickness that was more mildly reduced than that of homozygous mutation carriers. In affected members of another consanguineous Pakistani family with BCS (BC-002), Burkitt Wright et al. (2011) identified homozygosity for a nonsense mutation in PRDM5 (614161.0002). Further screening of patient samples identified homozygous mutations in PRDM5 in 5 additional BCS families, including 2 families previously studied by Cameron (1993) (see, e.g., 614161.0003-614161.0005). Burkitt Wright et al. (2011) noted that the phenotypic spectrum in BCS patients with mutations in either the ZNF469 (612078) or PRDM5 genes is extremely similar if not identical (see BCS1, 229200), suggesting that the 2 genes act within the same developmental pathway; expression microarray analysis confirmed that both genes participate in a pathway regulating expression of extracellular matrix components. In a 2-year-old Saudi girl with BCS2, born of healthy, first-cousin parents, Aldahmesh et al. (2012) identified a homozygous mutation in the PRDM5 gene (614165.0006). The parents were heterozygous for the mutation.