Cryptic chromosome rearrangements have been detected in developmentally delayed and/or dysmorphic individuals with normal karyotypes using conventional cytogenetic techniques. We report on a 10-month-old boy with bilateral cleft lip, cleft palate, strabismus, moderate bilateral hydroureteronephrosis, unilateral cryptorchidism, reduced growth, delayed development, and dysmorphic features, including upslanting palpebral fissures, bilateral epicanthic folds, a broad nasal bridge, fifth finger clinodactyly, and hypoplastic fifth fingernails. High-resolution G-banded chromosome analysis showed a 46,XY karyotype. However, FISH analysis with subtelomeric probes revealed a deletion of the 17p telomere without evidence of additional chromosome imbalance. Subtelomeric probe analysis in the parents showed a 17p telomere deletion in his phenotypically normal mother. Array comparative genomic hybridization analysis on the patient and his mother is pending. Telomere deletions have been described in phenotypically normal individuals, emphasizing the importance of differentiating pathogenic telomeric imbalance from benign familial variants or copy number variants in the population. In particular, paternally inherited deletions of the 17p telomere up to 600 kb in size have been described in individuals with no identifiable phenotype (Martin et al. J Med Genet 2002;39:734). The variability between the patient's and his mother's phenotype may result from unmasking of a recessive allele(s), modifier genes, environmental influences, or a difference in the size of their respective deletions. Our case provides additional evidence that the distal 17p13 telomeric region may represent an area of the genome in which reduced gene dosage can still be associated with a normal phenotype.
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