Beckwith–Wiedemann‐like macroglossia and 18q23 haploinsufficiency

Abstract

Beckwith-Wiedemann syndrome (BWS) is an overgrowth condition with tumor proclivity linked to a genetic imbalance of a complex imprinted region in 11p15.5. A female child with features fitting in with the BWS diagnostic framework and an apparent loss of imprinting (LOI) of the IGF2 gene in 11p15.5 was also reported to have a de novo chromosome 18q segmental deletion (Patient 1), thus pointing at the location of a possible trans-activating regulator element for maintenance of IGF2 imprinting and providing one of the few examples of locus heterogeneity of BWS. A second child with de novo 18q23 deletion and features of macroglossia, naevus flammeus, bilateral inguinal hernia and transient neonatal hypoglycemia, thus also fitting in with the BWS diagnostic framework, is here fully reported (Patient 2). In this child, an analysis of the BWS1 locus precluded any paternal isodisomy and showed a normal imprinting pattern (mono-allelic expression of IGF2 and normal H19 and CDKN1OT1/LIT1 methylation index). In Patients 1 and 2, deletions were shown to overlap, defining a minimal region of haplo-insufficiency of 3.8-5.6 Mb in 18q23. We conclude that this region provides a candidate location for an original macroglossia condition with strong overlap with BWS, but without obvious upstream functional relationship with the BWS1 locus in 11p15.5. Because this minimal region of haplo-insufficiency falls into a common region of deletion in 18q- syndrome, we inferred that this macroglossia condition would follow a recessive pattern of inheritance.

Beckwith–Wiedemann syndrome

“…Another locus possibly relevant to BWS has been suggested by reports of BWS‐like phenotype including macroglossia and deletions of the telomeric‐end of the long arm of chromosome 18 [Lirussi et al, 2007]. There is no obvious upstream functional relationship currently known between chromosome 18q and the BWS locus on chromosome 11p15.5.…”

Clinical and Cytogenomic Characterization of De Novo 11p14.3-p15.5 Duplication Associated with 18q23 Deletion in an Egyptian Female Infant

“…7,[12][13][14] Our patient represents only the fourth patient reported with both 11p duplication and 18q deletion, and all had manifestations of BWS (►Table 3). 12,15,16 The major BWS manifestations of macrosomia, macroglossia, and ear lobe crease were present in our patient. The size of the deleted 18q segment in these three patients (►Table 3) ranged from 0.6 to 18.4 Mb.…”

“…The size of the deleted 18q segment in these three patients (►Table 3) ranged from 0.6 to 18.4 Mb. 12,16 Another patient had a deletion of 3.8 to 5.6 Mb, 16 while our patient had a 3.7-MB deletion. Our patient and one other 12 demonstrated both the 11p duplication and 18q deletion, while the remaining two patients 16 only had the 18q deletion.…”

13q31.1 microdeletion: A prenatal case report with macrocephaly and macroglossia

“…Other rarer etiologies have been also involved in isolated or syndromic macroglossia (Prada et al, 2012). Few microdeletions in 9q34, 18q23 or 12q21.31 have been associated with a large protruding tongue in patients (Yatsenko et al, 2005;Lirussi et al, 2007;Baple et al, 2010) as well as some RASopathies, a family of pathologies linked to abnormalities of Ras/ mitogen activated protein kinase (MAPK) signaling pathway (Prada et al, 2012). Interestingly, some RASopathies such as Costello syndrome include macrocephaly as a key prenatal sign (Lin et al, 2009;Myers et al, 2014), a feature found in our presented case.…”