TANDEM DUPLICATION OF CHROMOSOME 1q IN FRYNS SYNDROME

Abstract

A newborn male with Fryns syndrome (FS), a lethal autosomal recessive condition, also had mosaic tandem duplication of chromosome 1q. Multiple malformations were noted at birth including diaphragmatic hernia, cleft palate, microglossia, hypoplastic digits, micrognathia, long philtrum, thin upper lip and short nose. The baby died at 5 hrs. of age. Autopsy revealed absent right middle lobe, bilateral renal cysts, hypoplastic renal arteries, urethral stricture, hydronephrosis and aortic coarctation. Chromosome analysis showed an abnormal constitution in 63% of lymphocytes: 46,XY/46,XY, dup(l) (q24q31.2). Parental chromosomes were normal.Possible explanations for a chromosomal abnormality in an autosomal recessive syndrome are (1) the chromosome anomaly could be coincidental, (2) partial trisomy for 1q could produce a phenocopy, (3) the gene for FS may be on 1q. This structural abnormality could have transformed a heterozygous carrier state into an hemizygous state with full expression of FS by disrupting the normal allele. Alternatively, the abnormal allele may have been amplified by the duplication here. This case poses many interesting questions regarding the relationship between chromosomal anomalies and mendelian traits.