Trisomy of the short arm of chromosome 5 due to a de novo inversion and duplication (5)(p15.3 p13.3)

Abstract

Partial trisomies of the short arm of chromosome 5 are uncommon. The first description was made by Lejeune et al., in 1964. It has been suggested that the critical region for 5p trisomy syndrome lies between 5p10 and 5p13. We report on a Mexican girl who developed severe mental retardation and generalized tonic clonic seizures at age 1 year. On physical examination at age 5 years, she had macrodolichocephaly, upslanted palpebral fissures, bilateral inner epicanthic folds, low nasal root, and malformed ears with posterior rotation which are clinical characteristics of 5p trisomy syndrome. The cytogenetic study with G bands and FISH with painting for chromosome 5 and with the cri-du-chat 5p15 unique sequence probe showed a duplication and inversion of 5p [46,XX, dup(5)(p15.3 p13.3)] which overlaps with the critical region for 5p trisomy syndrome. Our patient shares clinical characteristics with the patients described in the literature with involvement of this critical region. Both parents have normal karyotypes indicating the rearrangement is de novo. Only one patient has been reported in the literature with the same cytogenetic rearrangement as our patient, but this patient had a different phenotype. Since they only performed conventional cytogenetics and we performed FISH to confirm the diagnosis, the differences in the phenotypes could be explained by the presence of other genes involved in the rearrangement. The combined use of conventional and molecular cytogenetics in this case allows a more precise diagnosis and furthers knowledge in phenotype/genotype correlation.

Partial 5p monosomy or trisomy in 11 patients from a family with a t(5;15)(p13.3;p12) translocation

“…As our patients presented moderate mental retardation, hypotonia and macrodolicocephaly, bulbous nose, long philtrum, high-arched palate, macroglossia and microretrognathia, the region 5p13.3 is probably involved in these features. On the other hand, a trisomy distal to 5p13.3 is believed to be responsible for minor malformations and learning disabilities (Riordan et al 2002;Baialardo et al 2003;Cervera et al 2005). Our trisomic patients also showed midface hypoplasia, low-set hair line, dental malformations, Xat feet, abdominal muscular hypoplasia, and premature aging in the adults, features probably associated with duplication of the distal regions of 5p13.2.…”

“…The patients may show duplications distal to 5p13.3 (Chia et al 1987;Webb et al 1988;Zenger-Hain et al 1993), complete 5p duplication (Reichenbach et al 1999;Velagaleti et al 2000;Grosso et al 2002), and duplication of the 5p proximal region encompassing 5p10 to 5p13 (Lorda-Sanchez et al 1997;Avansino et al 1999;D'Amato Sizonenko et al 2002). Literature shows that patients with duplications distal to 5p13.3 (Baialardo et al 2003;Cervera et al 2005) present a relatively milder phenotype compared to complete 5p duplications (Reichenbach et al 1999;Velagaleti et al 2000;Grosso et al 2002) and to duplications of the proximal regions 5p11-5p13.2, suggesting a critical region between 5p10 and 5p13.1 (Lorda-Sanchez et al 1997;Avansino et al 1999;D'Amato Sizonenko et al 2002). In this paper we describe eleven alive aVected individuals with partial 5p monosomy or trisomy resulting from a familial balanced translocation t(5;15)(p13.3;p12).…”

Partial Chromosome Deletion: A New Trisomy Rescue Mechanism?

“…Cases of s-SMC of human chromosome 5 have been reported [15] , and the clinical severity was linked to the size and the level of mosaicism of the marker chromosomes. Partial duplication of the short arm [16] and long arm have also been reported but involve only a small part of human chromosome 5. Band 5p13 may be the determinant of clinical severity in 5p duplications.…”

Familial transmission of 5p13.2 duplication due to maternal der(X)ins(X;5)

“…Earlier studies of karyotypically visible duplications generated a clinical picture that included developmental delay, seizures, brain abnormalities, heart defects, hypotonia, clubfeet, and respiratory difficulties [Avansino et al, 1999;Cervera et al, 2005;LordaSanchez et al, 1997;Loscalzo et al, 2008;Rethore et al, 1989;Stankiewicz et al, 2000;Valcarcel et al, 1983]. Dysmorphic features included macrocephaly, frontal bossing, micrognathia, flat nasal bridge, apparent hypertelorism, and dysplastic ears [Avansino et al, 1999;Cervera et al, 2005;Lorda-Sanchez et al, 1997;Loscalzo et al, 2008;Rethore et al, 1989;Stankiewicz et al, 2000;Valcarcel et al, 1983].…”