Nevoid basal cell carcinoma (Gorlin) syndrome

Gorlin, Robert J.

doi:10.1097/01.gim.0000144188.15902.c4

Cited by 322 publications

(207 citation statements)

References 73 publications

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“…When compared to the previous reports of the literature, our case is particular and resembles an iatrogenic acquired Chiari I malformation for many reasons: (a) the LP shunt was valveless, (b) the shunt was inserted in infancy for macrocephaly that was supposed to be subsequent to the enlargement of the subarachnoid spaces, (c) macrocephaly was in fact the skeletal manifestation of a genetic disorder (Gorlin’s syndrome), (d) there was no previous tonsillar herniation, (e) tonsillar herniation has not been previously related to Gorlin’s syndrome [20], (f) the development of a Chiari I malformation and syringomyelia was induced by the valveless LP shunt with a mechanism of chronic CSF hypotension. The continuous lumbar drainage of CSF induced by the shunt resulted in a chronic negative pressure gradient between the cranial and spinal compartments that created the force responsible for the downward displacement of the tonsils and finally the tonsillar herniation [10, 12].…”

Section: Discussionmentioning

confidence: 99%

Acquired Chiari I Malformation and Syringomyelia after Valveless Lumboperitoneal Shunt in Infancy

Riffaud¹,

Moughty²,

Henaux³

et al. 2008

Pediatr Neurosurg

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The authors present the case of a 13-year-old boy who experienced frequent disabling episodes of typical postural induced headaches, which revealed a Chiari I malformation, syringomyelia and cervical spinal cord edema. This boy had received a valveless lumboperitoneal (LP) shunt at the age of 18 months for macrocephaly. At this time, cranial CT scan showed moderate enlargement of the subarachnoid spaces without hydrocephalus or tonsillar herniation. The LP shunt was clamped but the patient experienced signs of brain stem dysfunction and increased intracranial pressure. Finally, an adjustable valve (110 mm Hg) was inserted and all the symptoms resolved. Although some authors consider LP shunt as a safe and effective procedure even in the pediatric population, our case reminds us that these shunts, especially when valveless, may expose the patient to the risk of symptomatic acquired Chiari I malformation and syringomyelia consecutive to a chronic spinal CSF leakage.

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Section: Discussionmentioning

confidence: 99%

Acquired Chiari I Malformation and Syringomyelia after Valveless Lumboperitoneal Shunt in Infancy

Riffaud¹,

Moughty²,

Henaux³

et al. 2008

Pediatr Neurosurg

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“…Germline PTCH1 mutations result in nevoid basal cell carcinoma syndrome, also known as Gorlin's syndrome, which is characterized by cutaneous basal cell carcinomas (BCC), jaw cysts, skeletal abnormalities, and occasional cerebellar medulloblastoma [5,9,10]. Somatic inactivating PTCH1 mutations have been detected in various tumors, including BCC, medulloblastoma, meningeoma, and breast cancer [5,[9][10][11][12][13][14].…”

Section: Introductionmentioning

confidence: 99%

Downregulation of the hedgehog receptor PTCH1 in colorectal serrated adenocarcinomas is not caused by PTCH1 mutations

et al. 2011

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Colorectal serrated adenocarcinoma forms about 15-20% of colorectal carcinomas. We have previously shown that downregulation of PTCH1 is distinctive for this type of colorectal cancer. In several other tumor types, somatic inactivating PTCH1 mutations have been shown to lead to aberrant Hedgehog signaling, but in colorectal cancer the role of PTCH1 mutations has not been thoroughly studied. Here, we have analyzed the mutation status of PTCH1 in a series of 33 colorectal serrated adenocarcinomas by sequencing all 23 coding exons. We detected 11 previously known SNPs and eight new alterations. The latter included five synonymous changes and two previously unknown missense variations, somatic M319V, and germline V1231A. V1231A was also present in population controls and likely represents polymorphism. The somatic M319V variant does not appear to be an attractive candidate for a disease-associated mutation because in silico analyses did not support the pathogenic nature of the change. A somatic, intronic 1-bp deletion was detected in a short poly(T) stretch in two microsatellite unstable tumors. None of the three changes had predicted effect on splicing when analyzed in silico. Our results did not reveal any clearly deleterious inactivating PTCH1 mutations in our collection of colorectal serrated adenocarcinomas. This suggests that other mechanisms are involved in the observed downregulation of the PTCH1 gene. These might include, e.g., constantly active MAPK signaling by KRAS or BRAF mutations or silencing of PTCH1 by hypermethylation, and further studies are needed to reveal these mechanisms.

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“…Interestingly, Hh signal alterations are associated with as yet unexplained body size phenotypes. Murine models of Hh signal alteration have been described as having a growth alteration (Milenkovic et al 1999) and increased body size is seen in the human syndrome nevoid BCC syndrome in which patients carry a heterozygote Ptch1 mutation (Gorlin 2004). Gorlin syndrome patients' carry whole body heterozygote Ptch1 mutation, quite different from the BCC model discussed within this work, which has epithelial specific homozygous Ptch1 mutation.…”

Section: Discussionmentioning

confidence: 45%

Murine basal cell carcinoma leads to tumor-mediated alterations in endocrine Igf1 signaling

Villani

Waters

Wainwright

2013

Endocrine-Related Cancer

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The intrinsic properties underlying cancer development are extensively studied while the effect of a cancer on the host is often overlooked. Activation of the Hedgehog (Hh) signaling pathway underlies a number of types of common human cancers, yet little is known concerning endocrine signaling in such tumors. Here, we investigated endocrine signaling in a murine model of basal cell carcinoma (BCC) of the skin, the most common cancer. BCCs were generated by the activation of Hh signaling resulting from the specific deletion of the Ptch1 gene in the developing epidermis. Subsequently, a severe growth deficiency was observed in the murine BCC model, and we identified a deficiency of circulating IGF1 (Igf1). We demonstrate that Hh pathway activation in murine BCC induces IGF binding proteins, thereby regulating Igf1 sequestration into the skin and skewing Igf endocrine signaling. Significantly, these results show that Hh-induced tumors can have endocrine effects on normal tissues that in turn can greatly impact the host. This study not only identifies that Igf is important in Hh-associated skin tumors but also exemplifies the need to consider endocrine signaling when interpreting complex in vivo tumor models.

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Nevoid basal cell carcinoma (Gorlin) syndrome

Cited by 322 publications

References 73 publications

Acquired Chiari I Malformation and Syringomyelia after Valveless Lumboperitoneal Shunt in Infancy

Acquired Chiari I Malformation and Syringomyelia after Valveless Lumboperitoneal Shunt in Infancy

Downregulation of the hedgehog receptor PTCH1 in colorectal serrated adenocarcinomas is not caused by PTCH1 mutations

Murine basal cell carcinoma leads to tumor-mediated alterations in endocrine Igf1 signaling

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