Wolf–Hirschhorn syndrome facial dysmorphic features in a patient with a terminal 4p16.3 deletion telomeric to the WHSCR and WHSCR 2 regions

Engbers, Hannelie M.; Smagt, Jasper J. van der; Slot, Ruben van ‘t; Vermeesch, Joris Robert; Hochstenbach, Ron; Poot, Martin

doi:10.1038/ejhg.2008.168

Cited by 57 publications

(62 citation statements)

References 12 publications

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“…A1 and A2 are in a grey area, but could not be given a diagnosis of WHS. MT1's deletion involves FGFRL1 alone, but does appear to produce some WHS facial characteristics, as was suggested for the patient in Engbers et al, 22 whom we have not analysed. Thus, the loss or disruption of FGFRL1 or WHSC1 alone does affect facial morphology, with FGFRL1 possibly having a slightly greater effect.…”

Section: Facial Dysmorphology In Whs Is Visualized Effectively Using mentioning

confidence: 64%

“…It has been suggested that the facial phenotype arises from loss of WHSC1, 20 but a later communication 21 reported one patient without the facial phenotype with WHSC1 deleted and another patient with the facial phenotype, but with WHSC1 retained. Two recent studies 22,23 have suggested that the fibroblast growth factor receptor FGFRL1 is involved in the aetiology of WHS and in particular influences craniofacial development. Figure 1a shows the relative positions of FGFRL1, LETM1, WHSC1 and WHSC2 in 4p16.…”

Section: Wolf-hirschhorn Syndrome (Whs; Omim 194190) Is a Contiguous mentioning

confidence: 99%

“…Also represented in the figure is the case where a role for FGFRL1 in the WHS facial phenotype was first proposed. 22 This patient has a terminal deletion with a breakpoint in between those of MT1 and A2. Supplementary Table ST1 gives more detailed descriptions of the breakpoints for these six individuals.…”

Section: Cases A3 and Ma3mentioning

confidence: 99%

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Fine-grained facial phenotype–genotype analysis in Wolf–Hirschhorn syndrome

Hammond¹,

Hannes

Suttie³

et al. 2011

Eur J Hum Genet

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Wolf-Hirschhorn syndrome is caused by anomalies of the short arm of chromosome 4. About 55% of cases are due to de novo terminal deletions, 40% from unbalanced translocations and 5% from other abnormalities. The facial phenotype is characterized by hypertelorism, protruding eyes, prominent glabella, broad nasal bridge and short philtrum. We used dense surface modelling and pattern recognition techniques to delineate the milder facial phenotype of individuals with a small terminal deletion (breakpoint within 4p16.3) compared to those with a large deletion (breakpoint more proximal than 4p16.3). Further, fine-grained facial analysis of several individuals with an atypical genotype and/or phenotype suggests that multiple genes contiguously contribute to the characteristic Wolf-Hirschhorn syndrome facial phenotype.

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Section: Facial Dysmorphology In Whs Is Visualized Effectively Using mentioning

confidence: 64%

Section: Wolf-hirschhorn Syndrome (Whs; Omim 194190) Is a Contiguous mentioning

confidence: 99%

See 1 more Smart Citation

Fine-grained facial phenotype–genotype analysis in Wolf–Hirschhorn syndrome

Hammond¹,

Hannes

Suttie³

et al. 2011

Eur J Hum Genet

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show abstract

“…1,8,16 Furthermore, not all patients with deletions overlapping both WHSC1 and LETM1 express the full WHS phenotype 1,12,13 and deletions elsewhere in 4p16.3 have been identified in patients with features overlapping WHS. 1, [21][22][23][24] Altogether, these findings suggest that multiple loci within the B0.4-2.0 Mb terminal region of 4p16.3 contribute to WHS.…”

Section: Introductionmentioning

confidence: 79%

“…In the literature, there are several reports of patients with atypical 4p16.3 deletions and a facial profile similar to WHS, 12,19,21,23,24 suggesting that multiple genes contribute to the WHS gestalt. In addition to WHSC1, the gene fibroblast growth factor receptor-like 1 (FGFRL1) has also been associated with craniofacial development phenotypes in the mouse.…”

Section: Discussionmentioning

confidence: 99%

Deletions involving genes WHSC1 and LETM1 may be necessary, but are not sufficient to cause Wolf–Hirschhorn Syndrome

et al. 2013

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Wolf-Hirschhorn syndrome (WHS) is a complex genetic disorder caused by the loss of genomic material from the short arm of chromosome 4. Genotype-phenotype correlation studies indicated that the loss of genes within 4p16.3 is necessary for expression of the core features of the phenotype. Within this region, haploinsufficiency of the genes WHSC1 and LETM1 is thought to be a major contributor to the pathogenesis of WHS. We present clinical findings for three patients with relatively small (o400 kb) de novo interstitial deletions that overlap WHSC1 and LETM1. 3D facial analysis was performed for two of these patients. Based on our findings, we propose that hemizygosity of WHSC1 and LETM1 is associated with a clinical phenotype characterized by growth deficiency, feeding difficulties, and motor and speech delays. The deletion of additional genes nearby WHSC1 and LETM1 does not result in a marked increase in the severity of clinical features, arguing against their haploinsufficiency. The absence of seizures and typical WHS craniofacial findings in our cohort suggest that deletion of distinct or additional 4p16.3 genes is necessary for expression of these features. Altogether, these results show that although loss-offunction for WHSC1 and/or LETM1 contributes to some of the features of WHS, deletion of additional genes is required for the full expression of the phenotype, providing further support that WHS is a contiguous gene deletion disorder.

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DELETION 4p

Battaglia¹

2020

Cassidy and Allanson's Management of Genetic Syndromes

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Wolf–Hirschhorn syndrome facial dysmorphic features in a patient with a terminal 4p16.3 deletion telomeric to the WHSCR and WHSCR 2 regions

Cited by 57 publications

References 12 publications

Fine-grained facial phenotype–genotype analysis in Wolf–Hirschhorn syndrome

Fine-grained facial phenotype–genotype analysis in Wolf–Hirschhorn syndrome

Deletions involving genes WHSC1 and LETM1 may be necessary, but are not sufficient to cause Wolf–Hirschhorn Syndrome

DELETION 4p

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