Diffuse Adenomatosis and Hepatocellular Carcinoma Treated with Liver Transplantation in an Adolescent Female with Kabuki Syndrome with a Novel <i>KMT2D</i> Gene Mutation

Timothy, Leander D; Lehrke, Heidi D.; Chandan, Vishal S.; Kolbe, Amy B.; Furuya, Katryn N.

doi:10.1155/2019/7983824

Cited by 9 publications

(13 citation statements)

References 18 publications

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“…This also regulates hepatic metabolism and coactivates PPARy2, which leads to increased bile acid levels, which have been linked to hepatic tumor development (unspecific marker). Whether or not KS should be considered a risk factor for hepatocellular carcinoma remains unknown [ 93 ]. The association between KS and autoimmune diseases has been described in the literature (see Immunology section) [ 94 ].…”

Section: Gastrointestinal (Gi) Issues In Kabuki Syndromementioning

confidence: 99%

“…She underwent donor liver transplantation. On biopsy, besides characteristics of hepatocellular carcinoma, the explanted liver exhibited hepatic adenomas with a low Ki-67 proliferation index [ 93 ]. The association between genetic syndromes and liver cancer has been suggested [ 93 , 159 ].…”

Section: Oncological Issues In Kabuki Syndromementioning

confidence: 99%

“…On biopsy, besides characteristics of hepatocellular carcinoma, the explanted liver exhibited hepatic adenomas with a low Ki-67 proliferation index [ 93 ]. The association between genetic syndromes and liver cancer has been suggested [ 93 , 159 ]. KMT2D has been shown to be mutated in hepatocellular carcinoma cases, and has even been suggested to be associated with earlier recurrence of disease, greater microvascular invasion and a more aggressive phenotype [ 93 , 160 ].…”

Section: Oncological Issues In Kabuki Syndromementioning

confidence: 99%

“…The association between genetic syndromes and liver cancer has been suggested [ 93 , 159 ]. KMT2D has been shown to be mutated in hepatocellular carcinoma cases, and has even been suggested to be associated with earlier recurrence of disease, greater microvascular invasion and a more aggressive phenotype [ 93 , 160 ]. It has also been suggested to disrupt the control of bile acid production in mutant mice [ 93 , 161 ].…”

Section: Oncological Issues In Kabuki Syndromementioning

confidence: 99%

“…KMT2D has been shown to be mutated in hepatocellular carcinoma cases, and has even been suggested to be associated with earlier recurrence of disease, greater microvascular invasion and a more aggressive phenotype [ 93 , 160 ]. It has also been suggested to disrupt the control of bile acid production in mutant mice [ 93 , 161 ]. Despite the cases above presenting a benign phenotype, the potential development of malignant liver cancer must be considered in KS patients.…”

Section: Oncological Issues In Kabuki Syndromementioning

confidence: 99%

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Kabuki Syndrome—Clinical Review with Molecular Aspects

Boniel

Sztefko

Śmigiel

et al. 2021

Genes

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Kabuki syndrome (KS) is a rare developmental disorder principally comprised of developmental delay, hypotonia and a clearly defined dysmorphism: elongation of the structures surrounding the eyes, a shortened and depressed nose, thinning of the upper lip and thickening of the lower lip, large and prominent ears, hypertrichosis and scoliosis. Other characteristics include poor physical growth, cardiac, gastrointestinal and renal anomalies as well as variable behavioral issues, including autistic features. De novo or inherited pathogenic/likely pathogenic variants in the KMT2D gene are the most common cause of KS and account for up to 75% of patients. Variants in KDM6A cause up to 5% of cases (X-linked dominant inheritance), while the etiology of about 20% of cases remains unknown. Current KS diagnostic criteria include hypotonia during infancy, developmental delay and/or intellectual disability, typical dysmorphism and confirmed pathogenic/likely pathogenic variant in KMT2D or KDM6A. Care for KS patients includes the control of physical and psychomotor development during childhood, rehabilitation and multi-specialist care. This paper reviews the current clinical knowledge, provides molecular and scientific links and sheds light on the treatment of Kabuki syndrome individuals.

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Section: Gastrointestinal (Gi) Issues In Kabuki Syndromementioning

confidence: 99%

Section: Oncological Issues In Kabuki Syndromementioning

confidence: 99%

Section: Oncological Issues In Kabuki Syndromementioning

confidence: 99%

Section: Oncological Issues In Kabuki Syndromementioning

confidence: 99%

Section: Oncological Issues In Kabuki Syndromementioning

confidence: 99%

See 3 more Smart Citations

Kabuki Syndrome—Clinical Review with Molecular Aspects

Boniel

Sztefko

Śmigiel

et al. 2021

Genes

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Molecular characterization of an embryonal rhabdomyosarcoma occurring in a patient with Kabuki syndrome: report and literature review in the light of tumor predisposition syndromes

et al. 2022

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Kabuki syndrome is a well-recognized syndrome characterized by facial dysmorphism and developmental delay/intellectual disability and in the majority of patients a germline variant in KMT2D is found. As somatic KMT2D variants can be found in 5–10% of tumors a tumor predisposition in Kabuki syndrome is discussed. So far less than 20 patients with Kabuki syndrome and a concomitant malignancy have been published. Here we report on a female patient with Kabuki syndrome and a c.2558_2559delCT germline variant in KMT2D who developed an embryonal rhabdomyosarcoma (ERMS) at 10 years. On tumor tissue we performed DNA-methylation profiling and exome sequencing (ES). Copy number analyses revealed aneuploidies typical for ERMS including (partial) gains of chromosomes 2, 3, 7, 8, 12, 15, and 20 and 3 focal deletions of chromosome 11p. DNA methylation profiling mapped the case to ERMS by a DNA methylation-based sarcoma classifier. Sequencing suggested gain of the wild-type KMT2D allele in the trisomy 12. Including our patient literature review identified 18 patients with Kabuki syndrome and a malignancy. Overall, the landscape of malignancies in patients with Kabuki syndrome was reminiscent of that of the pediatric population in general. Histopathological and molecular data were only infrequently reported and no report included next generation sequencing and/or DNA-methylation profiling. Although we found no strong arguments pointing towards KS as a tumor predisposition syndrome, based on the small numbers any relation cannot be fully excluded. Further planned studies including profiling of additional tumors and long term follow-up of KS-patients into adulthood could provide further insights.

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Benign liver lesions 2022: Guideline for clinical practice of Associazione Italiana Studio del Fegato (AISF), Società Italiana di Radiologia Medica e Interventistica (SIRM), Società Italiana di Chirurgia (SIC), Società Italiana di Ultrasonologia in Medicina e Biologia (SIUMB), Associazione Italiana di Chirurgia Epatobilio-Pancreatica (AICEP), Società Italiana Trapianti d'Organo (SITO), Società Italiana di Anatomia Patologica e Citologia Diagnostica (SIAPEC-IAP) – Part II - Solid lesions

Pompili

Ardito

Brunetti³

et al. 2022

Digestive and Liver Disease

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Diffuse Adenomatosis and Hepatocellular Carcinoma Treated with Liver Transplantation in an Adolescent Female with Kabuki Syndrome with a Novel KMT2D Gene Mutation

Cited by 9 publications

References 18 publications

Kabuki Syndrome—Clinical Review with Molecular Aspects

Kabuki Syndrome—Clinical Review with Molecular Aspects

Molecular characterization of an embryonal rhabdomyosarcoma occurring in a patient with Kabuki syndrome: report and literature review in the light of tumor predisposition syndromes

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