Abstract
Inverted duplication syndrome with an adjacent terminal deletion of the short arm of chromosome 8—inv dup del(8p)—is a rare complex structural chromosomal rearrangement with a wide range of clinical manifestations. Molecular cytogenetic variants of chromosomal imbalance depend on the mechanism of rearrangement formation. We analyzed the clinical–genetic and molecular cytogenetic characteristics of the 8p inverted duplication/deletion syndrome, as well as the genotype–phenotype correlation in eight unrelated cases with the rearrangement of inv dup del(8p). The main clinical manifestations in all cases are psychomotor and language delay, muscle hypotonia, and dysmorphic facial features. Malformations of the central nervous system, such as corpus callosum agenesis, were found in five cases. Seizures were reported in only one case. We found that the cause of the formation of the rearrangement was generally ectopic recombination (seven out of eight cases) and this was due to U-type exchange in only one case. Depending on the mechanism of formation, the characteristics of the genomic imbalance were different, which made it possible to identify two molecular cytogenetic variants in the cases we describe here. No association between molecular cytogenetic variants and clinical manifestations was found.
Highlights
Inverted duplication with an adjacent terminal deletion of the short arm of chromosome 8—inv dup del(8p), ORPHA 96092—is a rare complex constitutional structural chromosomal rearrangement with an estimated frequency of 1/10,000–1/30,000 of newborns [1,2]
The first clinical case was described in 1976 by Weleber et al They reported the birth of a patient with delayed psychomotor development and multiple developmental anomalies, including agenesis of the corpus callosum and cleft palate, and for the first time suggested a model for the formation of chromosomal imbalance [3]
The clinical manifestations of this chromosomal/genomic imbalance include mild-to-severe intellectual disability, characteristic dysmorphic facial features, CNS malformations such as hypoplasia/agenesis of the corpus callosum (67%), cardiovascular diseases (65%), musculoskeletal problems (59%), hypotonia (88%), and seizures (55%)
Summary
Inverted duplication with an adjacent terminal deletion of the short arm of chromosome 8—inv dup del(8p), ORPHA 96092—is a rare complex constitutional structural chromosomal rearrangement with an estimated frequency of 1/10,000–1/30,000 of newborns [1,2]. The first clinical case was described in 1976 by Weleber et al They reported the birth of a patient with delayed psychomotor development and multiple developmental anomalies, including agenesis of the corpus callosum and cleft palate, and for the first time suggested a model for the formation of chromosomal imbalance [3]. The clinical manifestations of this chromosomal/genomic imbalance include mild-to-severe intellectual disability, characteristic dysmorphic facial features, CNS malformations such as hypoplasia/agenesis of the corpus callosum (67%), cardiovascular diseases (65%), musculoskeletal problems (59%), hypotonia (88%), and seizures (55%). Dysmorphic facial features in individuals with inv dup del(8p) include microcephaly, large and prominent forehead, mildly arched eyebrows, deep-set eyes, ptosis or hooded eyelids, full cheeks, wide mouth, and micrognathia [4].
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