A Small Supernumerary Marker Derived from the Pericentromeric Region of Chromosome 5: Case Report and Delineation of Partial Trisomy 5p Phenotype

Abstract

A 17-year-old girl presented with a distinct phenotype mainly featuring craniofacial dysmorphism, including a disproportioned large, round, elongated face; hypertelorism; deep-set eyes with short palpebral fissures; obesity (BMI 37), and a neuropsychiatric disorder with high-functioning autism. Postnatal conventional cytogenetic analyses from peripheral blood revealed a mosaic small supernumerary marker chromosome (sSMC) with a mos 47,XX,+mar[7]/46,XX[43] karyotype. By cenM-FISH technique, the sSMC was identified as a ring derivative of chromosome 5. Metaphase FISH analysis with a set of dedicated probes defined its origin from the pericentromeric region of chromosome 5, including the NIPBL gene at 5p13.2. Such sSMCs, exceedingly rare in the literature, underlie proximal trisomy 5p. In order to delineate a core phenotype of proximal trisomy 5p, we compared our patient's features with those of 6 patients found in the literature with similar der(5) chromosomes. Furthermore, a dozen individuals with 5p13 (micro)duplication syndrome was compared and discussed. We identified highly distinctive craniofacial dysmorphism, obesity, and intellectual disability and/or autism spectrum disorder as typical features of proximal 5p trisomy. In the critical region (band 5p13), the NIPBL gene is likely to be a major determinant of the neurobehavioral phenotype, and its presence at the sSMC level may be relevant to predict clinical outcome.

First case of two supernumerary markers derived from chromosome 5 and chromosome 8

“…A critical region has been proposed for 5p13, which, in trisomy, is associated with pregnancy complicated by polyhydramnios, psychomotor delay and characteristic facial features. Of the ten reported cases with a molecular cytogenetic content overlapping our case, six involve 5p-arm euchromatic content, namely, the critical region proposed for 5p13, and euchromatic material from 5q-arm (Stankiewicz et al [ 5 ] (case 1); D’Amato Sizonenko et al [ 9 ] (case 2); Sarri et al [ 10 ]; Hadzsiev et al [ 13 ]; Camerota et al [ 14 ] and Armstrong et al [ 4 ]). The dysmorphic features of these cases are concordant with the ones described for trisomy involving 5p13 (Avansino et al [ 7 ]; D’Amato Sizonenko et al [ 9 ] (case 1)).…”

“…82% of patients presented macrocephaly [ 4 , 7 , 9 – 11 , 13 , 14 ], 91% have hypertelorism [ 7 – 14 ], 63% have upslanted palpebral fissures [ 7 – 9 , 11 , 14 ], 54% have midface hypoplasia [ 4 , 7 , 9 , 13 ] and 73% have depressed nasal bridge [ 7 – 9 , 11 , 13 , 14 ].…”

Novel phenotype of 5p13.3-q11.2 duplication resulting from supernumerary marker chromosome 5: implications for management and genetic counseling

“… a Dysmorphic facial features described in individuals included dolichocephaly, epicanthal folds, upslanting palpebral fissures, hypertelorism, microphthalmia/coloboma, strabismus, broad nasal bridge, short nose, midface hypoplasia, macroglossia, microretrognathia, pre-auricular pits, and/or low-set/dysplastic ears [ 6 , 7 , 10 , 14 , 15 , 22 , 28 , 31 , 32 ]. “NR” represents that the feature was not reported in the publication …”