Partial tetrasomy 14 associated with multiple malformations

Abstract

We report on an 8-year-old female patient with multiple malformations including bilateral cleft lip and palate, coloboma, and craniosynostosis. She presented with severe intellectual disability, seizures, and gastrointestinal dysfunction. Mitochondrial investigations in a muscle biopsy revealed reduced activity in complex I of the mitochondrial respiratory chain. Chromosome analysis and fluorescent in situ hybridization (FISH) studies showed an isodicentric marker chromosome 14 that was identified in all cells analyzed in peripheral blood lymphocytes and cultured fibroblasts. Parental chromosome studies were normal. To further characterize the marker chromosome and determine its origin, we performed array-based comparative genomic hybridization (CGH) and polymorphic marker analysis with quantitative fluorescent PCR (QF-PCR). The combined results from cytogenetic and array-CGH analyses showed tetrasomy 14p13q13.1 and results from the QF-PCR point to formation of the marker chromosome in the maternal meiosis. Isodicentric chromosomes involving partial 14q have previously been reported in four cases; however, this is the first patient with tetrasomy 14p13q13.1 in non-mosaic form surviving beyond infancy.

The first de novo non‐mosaic 14q11.2q13.1 tetrasomy of paternal origin

“…To our best knowledge, this is the first report on a case of a non‐mosaic partial tetrasomy of chromosome 14 resulting from a triplication of paternal origin. The phenotype of our patient was severe and decidedly different from the previously published cases [Nuessle and Miles, ; George et al, ; Eggermann et al, ; Fdez‐Novoa et al, ; Schwanitz et al, ; Winberg et al, ]. None of the patients with tetrasomy 14q11q13 described before [Nuessle and Miles, ; George et al, ; Eggermann et al, ; Fdez‐Novoa et al, ; Schwanitz et al, ; Winberg et al, ] had blepharophimosis, small thorax, joint contractures, and our proband did not have cleft lip/palate nor iris coloboma.…”

“…The phenotype of our patient was severe and decidedly different from the previously published cases [Nuessle and Miles, ; George et al, ; Eggermann et al, ; Fdez‐Novoa et al, ; Schwanitz et al, ; Winberg et al, ]. None of the patients with tetrasomy 14q11q13 described before [Nuessle and Miles, ; George et al, ; Eggermann et al, ; Fdez‐Novoa et al, ; Schwanitz et al, ; Winberg et al, ] had blepharophimosis, small thorax, joint contractures, and our proband did not have cleft lip/palate nor iris coloboma. Interestingly, blepharophimosis, small thorax, and joint contractures were also seen in patients with paternal UPD cases reported so far [Sutton and Shaffer, ; Chu et al, ].…”

“…Tetrasomy 14q11q13 is a very rare chromosome aberration. Until now, only five patients were reported [Nuessle and Miles, ; George et al, ; Eggermann et al, ; Fdez‐Novoa et al, ; Schwanitz et al, ; Winberg et al, ]. All these patients had a marker chromosome idic(14)(q13) resulting in partial tetrasomy of chromosome 14.…”

“…All these patients had a marker chromosome idic(14)(q13) resulting in partial tetrasomy of chromosome 14. Reported abnormalities included craniosynostosis, a distinctive dysmorphic facial appearance with cleft lip and palate, coloboma of the iris, cardiac abnormalities, digital anomalies, growth retardation, intellectual disability [Winberg et al, ].…”

Different mutations inPDE4Dassociated with developmental disorders with mirror phenotypes

“…All experiments were performed according to the manufacturer's recommendations with minor modifications. Scanning and computational procedures have been described previously 8 – 10…”