Risk of malignancy in Sotos syndrome

Hersh, Joseph H.; Cole, Trevor; Bloom, Allan S.; Bertolone, Salvatore; Hughes, Helen E.

doi:10.1016/s0022-3476(10)80004-6

Cited by 99 publications

(56 citation statements)

References 7 publications

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“…It has also been observed that the incidence of cardiac abnormalities, such as arterial septal defect, ventricular septal defect and patent ductus arteriosus increase 10-fold in patients with Sotos syndrome [16], and since there is an increased risk for malignant tumors in Sotos syndrome, regular clinical examination of such patients has been emphasized [17, 18]. …”

Section: Discussionmentioning

confidence: 99%

A Case of Sotos Syndrome with Subduroperitoneal Shunt

Park

Park²,

Hwang³

et al. 2006

Pediatr Neurosurg

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The authors present a case of Sotos syndrome with increasing severity of subdural hygroma from the age of 5 months, which was managed with a subduroperitoneal shunt at 10 months of age. The patient had been followed up until 30 months of age with continuing improvement of symptoms. The patient initially presented with dolichocephaly accompanied by macrocrania, early tooth development, repeated pneumonia infections and developmental retardation concerning crawling, sitting, walking and speaking at 5 months of age. Magnetic resonance imaging (MRI) demonstrated partial hypoplasia of the corpus callosum and bifrontal subdural hygroma. The patient underwent subduroperitoneal shunting at 10 months of age with partial improvement of symptoms. At 18 months of age, the patient showed increased irritability and sweating, and development of spinal kyphosis, which resulted from shunt malfunction as shown in the shuntogram. The appearance of cervical syringomyelia was also seen in the MRI. After shunt revision, the irritability, sweating and kyphosis improved along with disappearance of the syringomyelia. The authors describe a case of Sotos syndrome with subduroperitoneal shunt that showed syringomyelia which developed with shunt malfunction but disappeared after shunt revision. We emphasize the importance of active management such as subduroperitoneal shunting to drain the cerebrospinal fluid in the Sotos syndrome.

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Section: Discussionmentioning

confidence: 99%

A Case of Sotos Syndrome with Subduroperitoneal Shunt

Park

Park²,

Hwang³

et al. 2006

Pediatr Neurosurg

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“…Mutations in NSD1 cause Sotos syndrome, a condition of childhood overgrowth and intellectual disability, with a 2.4% increased risk of childhood malignancy [45,46]. A chromosomal translocation resulting in the NUP98-NSD1 fusion protein is found in 16% of cytogenetically normal pediatric AML and in a smaller portion of adult AML [47].…”

Section: Nsd1: Activator Of Hox Genes In Leukemiamentioning

confidence: 99%

H3K36 Methyltransferases as Cancer Drug Targets: Rationale and Perspectives for Inhibitor Development

2016

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Methylation at histone 3, lysine 36 (H3K36) is a conserved epigenetic mark regulating gene transcription, alternative splicing and DNA repair. Genes encoding H3K36 methyltransferases (KMTases) are commonly overexpressed, mutated or involved in chromosomal translocations in cancer. Molecular biology studies have demonstrated that H3K36 KMTases regulate oncogenic transcriptional programs. Structural studies of the catalytic SET domain of H3K36 KMTases have revealed intriguing opportunities for design of small molecule inhibitors. Nevertheless, potent inhibitors for most H3K36 KMTases have not yet been developed, underlining the challenges associated with this target class. As we now have strong evidence linking H3K36 KMTases to cancer, drug development efforts are predicted to yield novel compounds in the near future. Cellular development and differentiation are controlled by post-translational modifications on DNA and histone proteins, forming an epigenetic (above the genes) regulatory network. Disruption of epigenetic pathways is a nearly universal feature of cancer, causing aberrations in gene expression and genome integrity (reviewed in [1]). A key group of epigenetic enzymes disrupted in cancer is the lysine methyltransferases (KMTases), which install methyl groups on histone proteins. In cancer cells, methylation performed by KMTases drives proliferation and halts differentiation by modifying gene transcription and other DNA-templated processes [2][3][4]. Over the past decade, KMTases have emerged as important drug targets for both industrial and academic research groups. Some progress has been made, most notably by selective inhibitors for the EZH2 and DOT1L KMTases that have reached clinical trials for the treatment of nonHodgkin lymphoma and acute leukemia, respectively [5,6]. Nevertheless, selective and cell permeable inhibitors for many KMTases remain unavailable.Methylation at H3K36 represents a particularly important chromatin mark implicated in diverse forms of cancer. KMTases with specificity toward H3K36 are overexpressed in cancer cells and have been characterized as regulators of cell growth, differentiation, stemness and DNA repair pathways [7][8][9]. However, very few selective and cell-active small molecule inhibitors of H3K36-specfic KMTases have been reported to date. In this article, we provide an overview of cellular pathways involving H3K36 methylation and discuss the diverse functions carried out by the eight different human H3K36-specific KMTases. Then we analyze structural characteristics of the catalytic SET domain of H3K36 KMTases and evaluate prospects for their inhibition by small molecules. Review Rogawski, Grembecka & Cierpicki We conclude with a discussion of the challenges and o pportunities for targeting these proteins. SPECIAL FOCUS y Epigenetic drug discovery H3K36 methylation regulates diverse processes implicated in cancerH3K36 methylation participates in a wide variety of nuclear pathways. Many of these processes, including transcriptional regulation, alternative spli...

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“…TAKAHASt-II et al with prominent forehead, down-slanting palpebral fissures, hypertelorism, prognathism, abnormal coordination, and variable degrees of mental retardation. Other occasional findings of the syndrome include urogenital anomalies (Moriyama et al, 1984), congenital heart defects (Kaneko et al, 1987), and malignancies (Dodge et al, I983;Hersh et al, 1992).…”

Section: Introductionmentioning

confidence: 99%