Background: Deletions involving the long arm of chromosome 18 have been associated with a highly variable phenotypic spectrum that is related to the extent of the deleted region. Duplications in chromosomal region 4p16.3 have also been shown to cause 4p16.3 microduplication syndrome. Most reported patients of trisomy 4p16.3 have more duplications, including the Wolf-Hirschhorn critical region (WHSCR). Here, we present a patient with speech delay and mental retardation caused by a deletion of 18q (18q22.1-qter) and terminal microduplication of 4p (4p16.3-pter) distal to WHSCR.
Case presentation: The patient was a 23-month-old boy with moderate growth retardation, severe speech delay, mental retardation, and dysmorphic features. Single nucleotide polymorphism (SNP) array analysis confirmed an 11.2-Mb terminal deletion at 18q22.1 and revealed a 1.8-Mb terminal duplication of 4p16.3. Our patient showed clinical overlap with these two syndromes, although his overall features were milder than what had been previously described. Some dosage-sensitive genes on the 18q terminal deleted region and 4p16.3 duplicated region of the present case may have contributed to his phenotype.
Conclusions: This is the first report of a patient with combined terminal deletion of 18q22.1 and duplication of 4p16.3. In this report, we provide clinical and molecular evidence supporting that the microduplication in 4p16.3, distal to WHSCR, is pathogenic. The coexistence of two chromosome aberrations complicates the clinical picture and creates a chimeric phenotype. This report provides further information on the genotype-phenotype correlation of 18q terminal deletion and 4p microduplication.
Keywords: 18q22.1 deletion; 4p16.3 duplication; Facial dysmorphisms; Mental retardation; Speech delay.