Zeiter (1963) described a family with bilateral microphthalmia, congenital cataract, and nystagmus in 7 members over 3 generations. Of the 4 affected family members in the youngest generation, 2 were mentally retarded and 1 of the latter also ... Zeiter (1963) described a family with bilateral microphthalmia, congenital cataract, and nystagmus in 7 members over 3 generations. Of the 4 affected family members in the youngest generation, 2 were mentally retarded and 1 of the latter also had congenital heart disease with presumed interventricular septal defect and patent ductus arteriosus as well as hydrocephalus and brain atrophy on ventriculogram. Temtamy and Shalash (1974) reported a 3-year-old Egyptian boy, born of first-cousin parents, with bilateral microphthalmia, cataracts, and nystagmus. An older sister, who died at age 3 of a 'severe chest infection,' was said to have had an identical phenotype. Gallardo et al. (2004) described an 18-year-old female who presented with congenital bilateral asymmetric microphthalmia, cataract, nystagmus, and syndactyly of toes 2/3. At 1 year of age, she underwent cataract extraction on her left eye with subsequent development of secondary glaucoma in that eye, which led to surgical removal and prosthetic replacement at age 7. At 11 years of age, growth, psychomotor development, and neurologic examination were normal, as was brain MRI; specifically, there were no abnormalities of the posterior pituitary gland (see MCOPS6, 607932). Gallardo et al. (2004) noted that isolated syndactyly of toes 2/3 is a frequent minor limb anomaly which they considered to be unrelated to the ocular phenotype of this patient.
In an 18-year-old female with bilateral microphthalmia, cataract, and nystagmus, Gallardo et al. (2004) identified heterozygosity for a missense mutation in the SIX6 gene (606326.0001). Her unaffected father also carried the mutation, which was not found in more ... In an 18-year-old female with bilateral microphthalmia, cataract, and nystagmus, Gallardo et al. (2004) identified heterozygosity for a missense mutation in the SIX6 gene (606326.0001). Her unaffected father also carried the mutation, which was not found in more than 160 control chromosomes. To explain the lack of abnormality in the father, Gallardo et al. (2004) suggested that the mutation may be on a different genetic background in the father than in the daughter or that the presence of a mutation in another gene in the daughter might have, in combination with the SIX6 mutation, resulted in the disease phenotype.