SUMMARY A family extending over 4 generations showed iridogoniodysgenesis accompanied by somatic malformations inherited in an autosomal dominant fashion. Iridogoniodysgenesis was present in 10 members, of whom 5 had established glaucoma; 4 youthful members are likely to develop glaucoma. Somatic malformations were present in 5 members from the 3rd and 4th generations who did not manifest iridogoniodysgenesis. A possible polygenic basis is discusssed, though the variable expression of an autosomal dominant inheritance is still the more likely explanation.The contribution of goniodysgenesis to the pathogenesis of hereditary juvenile glaucoma has been described. I2 The tern embraces a maldevelopment of the trabecular meshwork, hypoplasia of the anterior stromal layer of the iris, and anomaly of the peripheral cornea-Rieger's ocular malformation. For those patients in whom the iris hypoplasia is marked and comeal involvement absent iridogoniodysgenesis is the preferred descriptive term.3 Families with hereditary juvenile glaucoma are known in whom a dominantly inherited iridogoniodysgenesis is both prominent and a significant indicator of the accompanying glaucoma,47 but in none have somatic malformations been reported. We report a family over 4 generations showing marked iris hypoplasia present from birth accompanied by glaucoma in early adulthood, associated with somatic malformations of an autosomal dominant inheritance. Materials aind methodsAccess to the family was obtained via III ,0and siblings (Fig. 1). He had undergone bilateral thermal sclerostomy for the control of glaucoma at the age of 25 years and was seeking advice on behalf of his children.He was aware of a connection between iris colour and Correspondence to Dr 1. A.
A young man was diagnosed as having Zimmerman-Laband syndrome (ZLS) on the basis of gingival fibromatosis and absence of nails on thumbs and halluces in addition to other anomalies. He also had profound mental retardation.
The regions near telomeres of human chromosomes are gene rich. Chromosome subtelomere rearrangements occur with a frequency of 7–10% in children with mild‐to‐moderate mental retardation (MR) and approximately 50% of cases are familial. Clinical investigation of subtelomere rearrangements is now prompted by fluorescence in situ hybridization (FISH) analysis using specific DNA probes from all relevant chromosome ends. In our study, 40 children were selected for subtelomere assay using either the Chromophore Multiprobe‐T Cytocell device or the VYSIS TelVision probes. Inclusion criteria were: developmental delay or MR; a normal 550 G‐band karyotype; FRAXA negative; and at least one other clinical criterion. Exclusion criteria included an identified genetic or environmental diagnosis. Of the 40 patients analysed, four (10%) were found to have subtelomere rearrangements. Three of 40 (7.5%) were found to have an unbalanced subtelomere rearrangement and one of 40 (2.5%) was found to have an apparently normal variant subtelomere deletion. The first of the three with an unbalanced karyotype was the result of a familial translocation, the second was a de novo finding, and the origin of the third could not be determined. The subtelomere FISH assay detected almost twice the frequency of unbalanced karyotypes as those detected by 550 G‐banding in our cytogenetics laboratory (4.7%). In addition, subtelomere screening was eight times more likely than fragile X screening in our DNA laboratory (1%) to detect genetic abnormalities in mentally handicapped individuals. Our findings support the view that screening for subtelomere rearrangements has a greater positive yield than other commonly used genetic investigations and, if cost and resources permit, should be the next diagnostic test of choice in a child with unexplained MR/dysmorphisms and a normal 550 G‐band karyotype.
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