Carcinoma, and Cholestasis

PROGRESSIVE FAMILIAL INTRAHEPATIC CHOLESTASIS TYPE 4 Is also known as pfic4|tjp2 deficit

• Neoplasm
• Hypertension
• Jaundice
• Carcinoma
• Abnormality of the liver

SOURCES: ORPHANET OMIM MENDELIAN

• Short stature
• Neoplasm
• Failure to thrive
• Hepatomegaly
• Diarrhea

SOURCES: OMIM MENDELIAN

HBV is a DNA virus that enters the liver via the bloodstream, and replication occurs only in liver tissue. Transmission occurs by percutaneous or mucosal exposure to infected blood or other body fluids. Approximately one third of all cases of cirrhosis and half of all cases of hepatocellular carcinoma (HCC ) can be attributed to chronic HBV infection. Worldwide, 2 billion people have been infected with HBV, 360 million have chronic infection, and 600,000 die each year from HBV-related liver disease or HCC. However, there is marked geographic variability in HBV prevalence, with chronic infection affecting less than 2% of the populations of North America and western and northern Europe; between 2 and 7% of the populations of eastern and central Europe, the Amazon basin, the Middle East, and the Indian subcontinent; and more than 8% of the populations of Asia, sub-Saharan Africa, and the Pacific (Seeff and Hoofnagle, 2006; Shepard et al., 2006).

HEPATITIS B VIRUS, SUSCEPTIBILITY TO Is also known as hbv, susceptibility to

• Pain
• Hepatomegaly
• Fever
• Vomiting
• Splenomegaly

SOURCES: OMIM MENDELIAN

Karyomegalic interstitial nephritis is a rare, genetic renal disease characterized by slowly progressive, chronic, tubulointerstitial nephritis, leading to end-stage renal disease before the age of 50 years, manifesting with mild proteinuria, glucosuria and, occasionally, urinary sediment abnormalities (mainly hematuria). Mild extrarenal manifestations, such as recurrent upper respiratory tract infections and abnormal liver function tests, may be associated. Renal biopsy reveals severe, chronic, interstitial fibrosis and tubular changes, as well as hallmark karyomegalic tubular epithelial cells which line the proximal and distal tubules and have enlarged, hyperchromatic nuclei.

KARYOMEGALIC INTERSTITIAL NEPHRITIS Is also known as kin|systemic karyomegaly

• Anemia
• Hypertension
• Renal insufficiency
• Recurrent infections
• Pneumonia

SOURCES: OMIM ORPHANET MENDELIAN

Pancreatic cancer shows among the highest mortality rates of any cancer, with a 5-year relative survival rate of less than 5%. By the time of initial diagnosis, metastatic disease is commonly present. Established risk factors include a family history of pancreatic cancer, a medical history of diabetes type 2, and cigarette smoking (summary by Amundadottir et al., 2009). Genetic Heterogeneity of Pancreatic CancerSomatic mutations in pancreatic cancer occur in the KRAS (OMIM ), CDKN2A (OMIM ), MADH4 (OMIM ), TP53 (OMIM ), ARMET (OMIM ), STK11 (OMIM ), ACVR1B (OMIM ), and RBBP8 (OMIM ) genes.Susceptibility loci for pancreatic cancer include PNCA1 (OMIM ), related to mutation in the PALLD gene on chromosome 4q32 (OMIM ); PNCA2 (OMIM ), related to mutation in the BRCA2 gene on chromosome 13q12 (OMIM ); PNCA3 (OMIM ), related to mutation in the PALB2 gene on chromosome 16p12 (OMIM ); and PNCA4 (OMIM ), related to mutation in the BRCA1 gene on chromosome 17q21 (OMIM ). Occurrence of Pancreatic Cancer in Other DisordersSeveral familial cancer syndromes increase the risk of pancreatic cancer. The best characterized include hereditary nonpolyposis colon cancer syndrome (HNPCC; see {120435}); hereditary breast-ovarian cancer syndrome due to mutations in BRCA2; Peutz-Jeghers syndrome (OMIM ); the melanoma-pancreatic cancer syndrome (OMIM ), caused by mutations in CDKN2A (OMIM ); von Hippel-Lindau syndrome (OMIM ), ataxia-telangiectasia (OMIM ) (Swift et al., 1976), and juvenile polyposis syndrome (OMIM ).Patients with hereditary pancreatitis (OMIM ) resulting from gain-of-function mutations in the protease serine-1 gene (PRSS1 ) have a lifetime pancreatic cancer risk ratio of 57 and a cumulative incidence, to age 70 years, of 40% (Lowenfels et al., 1997).

PANCREATIC CANCER Is also known as pancreatic carcinoma|pancreatic acinar carcinoma

• Ataxia
• Neoplasm
• Pain
• Fatigue
• Diabetes mellitus

SOURCES: ORPHANET OMIM MENDELIAN

Budd-Chiari syndrome (BCS) is caused by obstruction of hepatic venous outflow involving either the hepatic veins or the terminal segment of the inferior vena cava.

• Neoplasm
• Pain
• Hypertension
• Hepatomegaly
• Fever

SOURCES: MESH OMIM ORPHANET MENDELIAN

Alpha-1-antitrypsin deficiency is a hereditary disease that develops in adulthood and is characterized by chronic liver disorders (cirrhosis), respiratory disorders (emphysema), and rarely panniculitis.

ALPHA-1-ANTITRYPSIN DEFICIENCY Is also known as deficiency in alpa-1-proteinase inhibitor

• Neoplasm
• Hypertension
• Hepatomegaly
• Fatigue
• Respiratory distress

SOURCES: ORPHANET MESH OMIM MENDELIAN

Progressive familial intrahepatic cholestasis is a heterogeneous group of autosomal recessive liver disorders characterized by early onset of cholestasis that progresses to hepatic fibrosis, cirrhosis, and end-stage liver disease before adulthood (Alonso et al., 1994; Whitington et al., 1994; Klomp et al., 2004). Genetic Heterogeneity of Progressive Familial Intrahepatic CholestasisPFIC is a genetically heterogeneous disorder caused by defects in the transport of bile acids. See also PFIC2 (OMIM ), caused by mutation in a liver-specific ATP-binding cassette transporter gene (ABCB11 ) on chromosome 2q24; PFIC3 (OMIM ), caused by mutation in the class III multidrug resistance P-glycoprotein gene (ABCB4 ) on chromosome 7q21; PFIC4 (OMIM ), caused by mutation in the TJP2 gene (OMIM ) on chromosome 9q12; and PFIC5 (OMIM ), caused by mutation in the NR1H4 gene (OMIM ) on chromosome 12q.PFIC1 and PFIC2 are associated with mildly elevated or normal serum levels of gamma-glutamyltransferase (GGT; see {612346}), whereas PFIC3 is associated with high serum GGT levels and liver histology that shows portal inflammation and ductular proliferation in an early stage ({27,26:Maggiore et al., 1987, 1991}). PFIC4 is associated with normal or mildly increased GGT levels (Sambrotta et al., 2014). PFIC5 is associated with low to normal GGT levels.There are also several phenotypically similar liver disorders that result from congenital defects in bile acid synthesis. See CBAS1 (OMIM ).

CHOLESTASIS, PROGRESSIVE FAMILIAL INTRAHEPATIC, 1; PFIC1 Is also known as byler disease

• Short stature
• Hearing impairment
• Growth delay
• Failure to thrive
• Sensorineural hearing impairment

SOURCES: OMIM MENDELIAN

Hereditary chronic pancreatitis (HCP), a rare inherited form of pancreatitis is defined as recurrent acute pancreatitis and/or chronic pancreatitis in two first-degree relatives or 3 or more second-degree relatives in 2 or more generations, for which no predisposing factors are identified. HCP is characterized by irreversible damage to both exocrine and endocrine components of the pancreas.

HEREDITARY CHRONIC PANCREATITIS Is also known as hp|pancreatitis, chronic|hpc

• Neoplasm
• Pain
• Fever
• Vomiting
• Diabetes mellitus

SOURCES: OMIM ORPHANET MENDELIAN