Dominant coloboma-microphthalmos syndrome associated with sensorineural hearing loss, hematuria, and cleft lip/palate

Abstract

Ocular colobomas and microphthalmos, isolated or as part of a syndrome, are usually sporadic and only rarely found in large families. A 4-generation family with autosomal dominant uveal coloboma and microphthalmos associated with cleft lip and palate was re-evaluated. Wide variability in expression is evident and more recently recognized manifestations include a complete spectrum of eye involvement, impairment of extraocular movement, mid-frequency sensorineural hearing loss, and hematuria. Learning difficulties requiring remedial teaching were present in one third of those affected and a neural tube defect has occurred in one presumed affected member. This family appears to present a unique phenotype, which provides an opportunity to identify a genetic locus involved in eye, ear, renal, primary palate, and brain development.

Gorlin syndrome: the PTCH gene links ocular developmental defects and tumour formation

“…It is now well established that microphthalmia with cyst is a developmental defect caused by failure of the optic fissure to close and forms part of the coloboma spectrum of ocular developmental anomalies. [1][2][3] The identification of a mutation within the PTCH gene, the gene known to give rise to Gorlin syndrome, highlights the importance of this gene in the ocular development gene pathway, particularly in the successful closure of the fetal fissure. The eye develops by a precisely orchestrated sequence of interdependent morphogenetic programmes allowing inductive interactions between tissues of different embryonic origin.…”

“…[1][2][3] Although microphthalmia with cyst is usually an isolated phenomenon, it can occur in association with systemic abnormalities notably clefting syndromes, oculo-cerebro-cutaneous syndrome, branchiooculo-facial syndrome, and cardiovascular anomalies including coarctation of the aorta and atrial septal defects. 4 However, any described conditions and genes (for example SHH (sonic hedgehog), or SIX3) associated with coloboma formation could in theory also be associated with microphthalmia or anophthalmia with cyst formation.…”

“…8 All inheritance patterns have been described for microphthalmia with coloboma, and in theory this could also be seen in microphthalmia with cyst formation. 1 9 10 Microphthalmia, with or without coloboma, is one of around 100 potential features seen in the naevoid basal cell carcinoma (BCC) syndrome or Gorlin syndrome, an autosomal dominant condition first described by Gorlin and Goltz. 11 12 The other ocular features include anterior segment dysgenesis with cataract and Peter's anomaly, and vitreoretinal anomalies including epiretinal membrane formation, myelinated nerve fibres, and persistent fetal hyaloid anomalies.…”

Studies of genes involved in craniofacial development and tumorigenesis:FGF3contributes to isolated oral clefts and may interact withPAX9

“…We are not aware of reports suggesting associations between these conditions and cleft lip and palate or cancer. However, at least one family segregating ocular coloboma and microphthalmos with cleft lip and palate in an autosomal dominant fashion has been reported [45].…”

Ocular colobomata, polydactyly, cleft palate and panhypopituitarism: a new syndrome

“…Ocular coloboma is a feature of numerous syndromes, some of which share features with our patient (Warburg et al, 1991;Ravine, 1997;Onwochei et al, 2000;Martin et al, 2001;Morrison et al, 2003;Gregory-Evans, 2004). Zuppinger and colleagues (1971) describe a case of hypothalamo-pituitary dysfunction and cleft lip with choroidal and optic disc colobomas.…”