Brittle cornea syndrome: recognition, molecular diagnosis and management

Table 1 Differential diagnosis of BCS: autosomal recessive connective tissue disorders with blue sclera and thin cornea

Condition / phenotype	OMIM	Gene	Protein	OMIM
BCS	229200	ZNF469	Zinc finger protein 469	612078
BCS	614170	PRDM5	PR domain containing 5	614161
EDS VI	225400	PLOD1	Lysyl hydroxylase 1	153454
EDS, musculocontractural type	601776	CHST14	Carbohydrate sulfotransferase 14	608429
EDS with progressive kyphoscoliosis, myopathy and hearing loss	614557	FKBP14	FK506 binding protein 14	614505
Bone fragility with contractures, arterial rupture and deafness	612394	PLOD3	Lysyl hydroxylase 3	603066
Spondylocheiro dysplastic type of EDS	612350	SLC39A13	ZIP3	608735

Other, rare, autosomal recessive forms of Ehlers Danlos syndrome (EDS) and osteogenesis imperfecta (OI) have also been characterised, but these would be unlikely to present within the differential diagnosis of BCS, for example the dermatosparactic form of EDS (VIIc, OMIM 604539, due to mutations in ADAMTS2[39]) has dramatic skin manifestations not seen to date in BCS patients, whilst the extremely rare patients with recessive OI due to biallelic mutations in collagen I or V genes have usually had severe bone fragility and again no dramatic eye phenotype reported. Recessive CRTAP mutations also appear to result in severe bone phenotypes but without significant ophthalmic complications [40], making it likely that these severe recessive OI presentations would be able to be differentiated from BCS.

ISSN: 1750-1172