Ataxia, and Abdominal pain

Low match PANCREATIC CANCER

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

Low match SPINOCEREBELLAR ATAXIA TYPE 25

Spinocerebellar ataxia type 25 (SCA25) is a very rare subtype of type I autosomal dominant cerebellar ataxia (ADCA type I; see this term). It is characterized by cerebellar ataxia and prominent sensory neuropathy.

SPINOCEREBELLAR ATAXIA TYPE 25 Is also known as sca25

• Scoliosis
• Ataxia
• Nystagmus
• Strabismus
• Visual impairment

SOURCES: OMIM MESH ORPHANET MENDELIAN

Low match CARBAMOYL-PHOSPHATE SYNTHETASE 1 DEFICIENCY

Carbamoyl-phosphate synthetase 1 deficiency (CPS1D) is a rare and severe disorder of urea cycle metabolism most commonly characterized by either a neonatal-onset of severe hyperammonemia that occurs few days after birth and manifests with lethargy, vomiting, hypothermia, seizures, coma and death or a presentation outside the newborn period at any age with (sometimes) milder symptoms of hyperammonemia.

CARBAMOYL-PHOSPHATE SYNTHETASE 1 DEFICIENCY Is also known as carbamoyl phosphate synthetase i deficiency|carbamoyl-phosphate synthetase deficiency|cps i deficiency|carbamoyl-phosphate synthetase i deficiency|cps1 deficiency|cps1d

• Intellectual disability
• Seizures
• Global developmental delay
• Ataxia
• Failure to thrive

SOURCES: OMIM ORPHANET MESH MENDELIAN

Low match NEUROBLASTOMA

Neuroblastoma is a malignant tumor of neural crest cells, the cells that give rise to the sympathetic nervous system, which is observed in children.

• Ataxia
• Neoplasm
• Failure to thrive
• Pain
• Anemia

SOURCES: ORPHANET OMIM MENDELIAN

Low match CYCLIC VOMITING SYNDROME; CVS

• Intellectual disability
• Seizures
• Global developmental delay
• Generalized hypotonia
• Hearing impairment

SOURCES: OMIM MENDELIAN

Low match MITOCHONDRIAL DNA DEPLETION SYNDROME 4B (MNGIE TYPE); MTDPS4B

Mitochondrial DNA depletion syndrome-4B is an autosomal recessive progressive multisystem disorder clinically characterized by chronic gastrointestinal dysmotility and pseudoobstruction, cachexia, progressive external ophthalmoplegia (PEO), axonal sensory ataxic neuropathy, and muscle weakness (van Goethem et al., 2003).For a discussion of genetic heterogeneity of autosomal recessive mtDNA depletion syndromes, see MTDPS1 (OMIM ).

MITOCHONDRIAL DNA DEPLETION SYNDROME 4B (MNGIE TYPE); MTDPS4B Is also known as mngie, polg-related|mitochondrial neurogastrointestinal encephalopathy syndrome, polg-related

• Seizures
• Global developmental delay
• Short stature
• Generalized hypotonia
• Hearing impairment

SOURCES: OMIM MENDELIAN

Low match LEGIONNAIRE DISEASE, SUSCEPTIBILITY TO

Legionnaire disease (LD) is a type of pneumonia caused by Legionella pneumophila, a flagellated gram-negative bacterium found primarily in warm water environments. The disease and the bacterium were discovered following an outbreak traced to a 1976 American Legion convention in Philadelphia. A number of risk factors for acquiring LD have been identified, including age, smoking, chronic lung disease, cancer, and immunosuppression (summary by Hawn et al., 2003).

• Ataxia
• Neoplasm
• Muscle weakness
• Pain
• Peripheral neuropathy

SOURCES: ORPHANET OMIM MENDELIAN

Low match DIHYDROLIPOAMIDE DEHYDROGENASE DEFICIENCY; DLDD

DLD deficiency is an autosomal recessive metabolic disorder characterized biochemically by a combined deficiency of the branched-chain alpha-keto acid dehydrogenase complex (BCKDC), pyruvate dehydrogenase complex (PDC), and alpha-ketoglutarate dehydrogenase complex (KGDC). This is the result of E3 being a common component of all 3 mitochondrial multienzyme complexes. Clinically, affected individuals have lactic acidosis and neurologic deterioration due to sensitivity of the central nervous system to defects in oxidative metabolism. E3 deficiency is often associated with increased urinary excretion of alpha-keto acids, such as pyruvate (summary by Hong et al., 1996). E3 deficiency can also be associated with increased concentrations of branched-chain amino acids, as observed in maple syrup urine disease (MSUD ), and is sometimes referred to as 'MSUD type III,' although patients with E3 deficiency have additional biochemical defects (Chuang and Shih, 2001; Robinson, 2001).

DIHYDROLIPOAMIDE DEHYDROGENASE DEFICIENCY; DLDD Is also known as maple syrup urine disease, type iii|e3 deficiency|lipoamide dehydrogenase deficiency, lactic acidosis due to|dld deficiency

• Seizures
• Global developmental delay
• Generalized hypotonia
• Hearing impairment
• Microcephaly

SOURCES: OMIM MENDELIAN

Low match HYPOCOMPLEMENTEMIC URTICARIAL VASCULITIS

Hypocomplementemic urticarial vasculitis (HUV) is an immune complex-mediated small vessel vasculitis characterized by urticaria and hypocomplementemia (low C1q with or without low C3 and C4), and usually associated with circulating anti-C1q autoantibodies. Arthritis, pulmonary disease, ocular inflammation, and glomerulonephritis are common systemic manifestations.

HYPOCOMPLEMENTEMIC URTICARIAL VASCULITIS Is also known as mac duffie syndrome|mac duffie hypocomplementemic urticarial vasculitis|anti-c1q vasculitis|mcduffie hypocomplementemic urticarial vasculitis|mcduffie syndrome

• Seizures
• Ataxia
• Sensorineural hearing impairment
• Pain
• Peripheral neuropathy

SOURCES: ORPHANET MENDELIAN

Low match GITELMAN SYNDROME; GTLMNS

Gitelman syndrome is an autosomal recessive renal tubular salt-wasting disorder characterized by hypokalemic metabolic alkalosis with hypomagnesemia and hypocalciuria. It is the most common renal tubular disorder among Caucasians (prevalence of 1 in 40,000). Most patients have onset of symptoms as adults, but some can present in childhood. Clinical features include transient periods of muscle weakness and tetany, abdominal pains, and chondrocalcinosis (summary by Glaudemans et al., 2012). Gitelman syndrome is sometimes referred to as a mild variant of classic Bartter syndrome (OMIM ).For a discussion of genetic heterogeneity of Bartter syndrome, see {607364}.

GITELMAN SYNDROME; GTLMNS Is also known as hypomagnesemia-hypokalemia, primary renotubular, with hypocalciuria|potassium and magnesium depletion

• Seizures
• Short stature
• Generalized hypotonia
• Ataxia
• Growth delay

SOURCES: ORPHANET OMIM MESH MENDELIAN