Oculoectodermal syndrome: Report of a new case with a broad clinical spectrum

Aslan, Deniz; Akata, Rüştü Fikret; Schröder, Julia; Happle, Rudolf; Moog, Ute; Bartsch, Oliver

doi:10.1002/ajmg.a.36727

Cited by 12 publications

(10 citation statements)

References 23 publications

(49 reference statements)

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“…The clinical phenotype of this 6 year old male was reported by Aslan et al as a case of OES . His clinical abnormalities included bilateral epibulbar dermoids, multiple areas of scalp alopecia, streaky areas of hypo‐ and hyperpigmentation following the lines of Blaschko, intellectual disability, and attention deficit hyperactivity disorder.…”

Section: Clinical Reportsmentioning

confidence: 59%

Specific mosaic KRAS mutations affecting codon 146 cause oculoectodermal syndrome and encephalocraniocutaneous lipomatosis

et al. 2016

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Oculoectodermal syndrome (OES) and encephalocraniocutaneous lipomatosis (ECCL) are rare disorders that share many common features, such as epibulbar dermoids, aplasia cutis congenita, pigmentary changes following Blaschko lines, bony tumor-like lesions, and others. About 20 cases with OES and more than 50 patients with ECCL have been reported. Both diseases were proposed to represent mosaic disorders, but only very recently whole-genome sequencing has led to the identification of somatic KRAS mutations, p.Leu19Phe and p.Gly13Asp, in affected tissue from two individuals with OES. Here we report the results of molecular genetic studies in three patients with OES and one with ECCL. In all four cases, Sanger sequencing of the KRAS gene in DNA from lesional tissue detected mutations affecting codon 146 (p.Ala146Val, p.Ala146Thr) at variable levels of mosaicism. Our findings thus corroborate the evidence of OES being a mosaic RASopathy and confirm the common etiology of OES and ECCL. KRAS codon 146 mutations, as well as the previously reported OES-associated alterations, are known oncogenic KRAS mutations with distinct functional consequences. Considering the phenotype and genotype spectrum of mosaic RASopathies, these findings suggest that the wide phenotypic variability does not only depend on the tissue distribution but also on the specific genotype.

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Section: Clinical Reportsmentioning

confidence: 59%

Specific mosaic KRAS mutations affecting codon 146 cause oculoectodermal syndrome and encephalocraniocutaneous lipomatosis

et al. 2016

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“…Since the initial report of OES [Toriello et al, 1993], 19 additional patients have been described [Evers et al, 1994;Gardner and Viljoen, 1994;Gunduz et al, 2000;Lees et al, 2000;Silengo et al, 2000;James and McGaughran, 2002;Federici et al, 2004;Lee et al, 2005;Martin et al, 2007;Ardinger et al, 2007;Horev et al, 2011;Fickie and Stoler, 2011;Trubnik et al, 2011;Aslan et al, 2014] with follow up details on two of them [Toriello et al, 1999;Horev et al, 2011]. All affected individuals were sporadic occurrences; prior to this report, the cause was unknown.…”

Section: Discussionmentioning

confidence: 95%

Oculoectodermal syndrome is a mosaic RASopathy associated with KRAS alterations

Peacock

Dykema

Toriello

et al. 2015

American J of Med Genetics Pt A

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Oculoectodermal syndrome (OES) is a rare disease characterized by a combination of congenital scalp lesions and ocular dermoids, with additional manifestations including non-ossifying fibromas and giant cell granulomas of the jaw occurring during the first decade of life. To identify the genetic etiology of OES, we conducted whole-genome sequencing of several tissues in an affected individual. Comparison of DNA from a non-ossifying fibroma to blood-derived DNA allowed identification of a somatic missense alteration in KRAS NM_033360.3(KRAS):c.38G>A, resulting in p.Gly13Asp. This alteration was also observed in the patient's other affected tissues including the skin and muscle. Targeted sequencing in a second, unrelated OES patient identified an NM_033360.3(KRAS):c.57G>C, p.Leu19Phe alteration. Allelic frequencies fell below 40% in all tissues examined in both patients, suggesting that OES is a mosaic RAS-related disorder, or RASopathy. The characteristic findings in OES, including scalp lesions, ocular dermoids, and benign tumors, are found in other mosaic and germline RASopathies. This discovery also broadens our understanding of the spectrum of phenotypes resulting from KRAS alterations. Future research into disease progression with regard to malignancy risk and investigation of RAS-targeted therapies in OES is warranted. KRAS sequencing is clinically available and may also now improve OES diagnostic criteria.

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“…In addition, all described cases of OES have shown some level of multi-organ involvement that include cardiovascular (coarctation of the aorta, atrial/septal defect), CNS (arachnoid cyst, seizures) and genitourinary system abnormalities (bladder exstrophy, epispadias), ( 97 - 99 ). Generally, individuals present with normal growth and neurocognitive development, but intellectual disability has been reported ( 98 , 99 ).…”

Section: Methodsmentioning

confidence: 99%

Giant Cell Lesions of the Jaws Involving RASopathy Syndromes

Luna¹,

Wolsefer²,

Zambrano³

et al. 2022

Acta Stomatol Croat

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Objective Giant cell lesions of the jaws (GCLJ) may rarely occur in the setting of RASopathy syndromes such as Noonan syndrome or neurofibromatosis I. Recently, central giant cell granulomas (CGCG), the most common of the GCLJ, have been recognized as benign neoplasms characterized by Ras/MAPK signaling pathway mutations. This provides a rational basis for understanding GCLJ in RASopathy syndromes as syndromically occurring CGCG. This review aims to summarize the clinicopathologic features of syndromic CGCG and to review the salient clinical and craniofacial features of the syndromes in which they may rarely occur. Material and Methods An electronic search in 3 databases was performed, looking for GCLJ/CGCG in RASopathy syndromes. Results 124 CGCG in 56 patients were identified across 6 RASopathy syndromes. Median age at syndromic CGCG diagnosis is 11 years; 69.6% (39/56) patients developed two or more CGCG; 58.9% (33/56) presented with bilateral posterior mandibular CGCGs, mimicking cherubism. Of 88 CGCG with follow-up, 22.4% (13/58) of excised/resected CGCG recurred while 46.7% (14/30) of monitored CGCG showed continued growth. Conclusion Syndromic CGCG involves multiple RASopathy syndromes and may mimic cherubism or, when solitary, sporadically occurring CGCG. Familiarity with other clinical findings of RASopathy syndromes is critical for appropriate diagnosis and patient management.

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Oculoectodermal syndrome: Report of a new case with a broad clinical spectrum

Cited by 12 publications

References 23 publications

Specific mosaic KRAS mutations affecting codon 146 cause oculoectodermal syndrome and encephalocraniocutaneous lipomatosis

Specific mosaic KRAS mutations affecting codon 146 cause oculoectodermal syndrome and encephalocraniocutaneous lipomatosis

Oculoectodermal syndrome is a mosaic RASopathy associated with KRAS alterations

Giant Cell Lesions of the Jaws Involving RASopathy Syndromes

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