Goldenhar syndrome and medulloblastoma: A coincidental association? The first case report

Aizenbud, Dror; Shoham, Natasha V.; Constantini, Shlomi; Nevo, Neta; Arush, Myriam Ben; Raz, Michal; Rachmiel, Adi; Goldsher, Dorit

doi:10.1016/j.jcms.2013.07.003

Cited by 3 publications

(3 citation statements)

References 55 publications

(59 reference statements)

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“…2,8,[16][17][18][19][20] Moreover, disagreement still exists whether lipodermoids are a part of the ocular manifestation, 4,21-23 and whether auricular appendices or preauricular fistula are also a part of the classification of Goldenhar syndrome. 3,21,24 -26 Additional diagnostic criteria reported previously in the literature as components of the Goldenhar syndrome include facial asymmetry, 3,27 ear anomalies in general, 27,28 cardiac and renal defects, [29][30][31] hypoplasia of the lungs, 29 upper lid coloboma, 21,22 microphtalmia, 26,32 and antimongoloid slant. 33 With all these different criteria described in literature, it is unclear which are truly diagnostic of Goldenhar syndrome.…”

Section: Discussionmentioning

confidence: 99%

Distinguishing Goldenhar Syndrome from Craniofacial Microsomia

Tuin

Tahiri

Paliga

et al. 2015

Journal of Craniofacial Surgery

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Goldenhar syndrome is characterized by the typical features of craniofacial microsomia (CFM) with the addition of epibulbar dermoids and vertebral anomalies. The aim of this study is to examine the objective differences between patients carrying a diagnosis of Goldenhar syndrome to those diagnosed with CFM. Thus, we performed an Institutional Review Board-approved retrospective chart review on all patients who presented with a diagnosis of CFM or Goldenhar syndrome from January 1990 to December 2012. Demographic, diagnosis, OMENS+ classification, accompanying diagnoses, and radiographic data were collected. For subjective analysis, subgroups were designed based on the diagnosis Goldenhar syndrome or CFM per history. For objective analysis, subgroups were designed based on the presence of epibulbar dermoids and/or vertebral anomalies. The cohorts were compared with respect to associated medical abnormalities and severity of CFM features. One hundred thirty eight patients met inclusion criteria. Epibulbar dermoids and vertebral anomalies were seen in 17% and 34% of the patients, respectively. Only 10 patients (7.2%) had both epibulbar dermoids and vertebral anomalies. The subjective "Goldenhar" group (N = 44, 32%) was found to have a higher percentage of bilaterally affected patients (P = 0.001), a more severe mandibular deformity (P = <0.001), a more severe soft tissue deformity (P = 0.01), and a higher incidence of macrostomia (P = 0.003). In the objective subgroup analysis, the only significant difference was found in the degree of soft tissue deficiency (P = 0.049). The diagnostic criteria of Goldenhar syndrome remain unclear, thereby making clinical use of the term "Goldenhar" inconsequential. Goldenhar syndrome is over diagnosed subjectively in patients who show more severe CFM features.

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Section: Discussionmentioning

confidence: 99%

Distinguishing Goldenhar Syndrome from Craniofacial Microsomia

Tuin

Tahiri

Paliga

et al. 2015

Journal of Craniofacial Surgery

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“…During the course of this study, at age seven, she was diagnosed with a medullosblastoma in the fourth ventricle. The tumor was completely resected, after which the child received craniospinal radiotherapy and chemotherapy [see a case study on her cancer treatment here: [20]].…”

Section: Resultsmentioning

confidence: 99%

“…Focal duplications and overexpression of this gene are prevalent in subclasses C and D of medulloblastoma [52]. Analysis of her tumor revealed an additional loss of heterozygosity on chromosome 17q [20] that is exclusively associated with subclasses C and D [52]. The potential biological link between OTX2 duplications in hemifacial microsomia and medulloblastoma raises the possibility of their comorbidity.…”

Section: Discussionmentioning

confidence: 99%

OTX2 Dosage Sensitivity is Implicated in Hemifacial Microsomia

Zielinski

Markus

Sheikh

et al. 2013

Preprint

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Hemifacial microsomia (HFM) is the second most common facial anomaly after cleft lip and palate. The phenotype is highly variable and most cases are sporadic. Here, we investigated the disorder in a large pedigree with five affected individuals spanning eight meioses. We performed whole-exome sequencing and a genome-wide survey of segmental variations. Analysis of the exome sequencing results indicated the absence of a pathogenic coding point mutation. Inspection of segmental variations identified a 1.3Mb duplication of chromosome 14q22.3 in all affected individuals that was absent in more than 1000 chromosomes of ethnically matched controls. The duplication was absent in seven additional sporadic HFM cases, which is concordant with the known heterogeneity of the disorder. To find the critical gene in the duplicated region, we analyzed signatures of human craniofacial disease networks, mouse expression data, and predictions of dosage sensitivity. All of these approaches implicated OTX2 as the most likely causal gene. Moreover, OTX2 is a known oncogenic driver in medulloblastoma, a condition that was diagnosed in the proband during the course of our study. Our findings highlight dosage sensitivity of OTX2 in human craniofacial development and suggest a possible shared etiology between a subtype of hemifacial microsomia and medulloblastoma.

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OTX2 Duplication Is Implicated in Hemifacial Microsomia

et al. 2014

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Hemifacial microsomia (HFM) is the second most common facial anomaly after cleft lip and palate. The phenotype is highly variable and most cases are sporadic. We investigated the disorder in a large pedigree with five affected individuals spanning eight meioses. Whole-exome sequencing results indicated the absence of a pathogenic coding point mutation. A genome-wide survey of segmental variations identified a 1.3 Mb duplication of chromosome 14q22.3 in all affected individuals that was absent in more than 1000 chromosomes of ethnically matched controls. The duplication was absent in seven additional sporadic HFM cases, which is consistent with the known heterogeneity of the disorder. To find the critical gene in the duplicated region, we analyzed signatures of human craniofacial disease networks, mouse expression data, and predictions of dosage sensitivity. All of these approaches implicated OTX2 as the most likely causal gene. Moreover, OTX2 is a known oncogenic driver in medulloblastoma, a condition that was diagnosed in the proband during the course of the study. Our findings suggest a role for OTX2 dosage sensitivity in human craniofacial development and raise the possibility of a shared etiology between a subtype of hemifacial microsomia and medulloblastoma.

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Goldenhar syndrome and medulloblastoma: A coincidental association? The first case report

Cited by 3 publications

References 55 publications

Distinguishing Goldenhar Syndrome from Craniofacial Microsomia

Distinguishing Goldenhar Syndrome from Craniofacial Microsomia

OTX2 Dosage Sensitivity is Implicated in Hemifacial Microsomia

OTX2 Duplication Is Implicated in Hemifacial Microsomia

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