Concomitant autoimmune disorders are common and include Sjögren's syndrome, CREST syndrome, autoimmune thyroid disease, rheumatoid arthritis and Raynaud syndrome, and often correlate with the autonomic dysfunction observed.
Description Primary biliary cirrhosis (PBC) is a chronic, progressive cholestatic liver disease that usually affects middle-aged women and eventually leads to liver failure (summary by Kaplan, 1996). For a discussion of genetic heterogeneity of primary biliary cirrhosis (PBC), see PBC1 (109720). Mapping To replicate the findings of Hirschfield et al. (2009) and to evaluate the relevance of identified loci to PBC susceptibility, Hirschfield et al. (2010) tested an additional independent cohort of 857 individuals with PBC and 3,198 controls, all of European descent, for PBC associations with 36 SNPs across 24 loci. The combination of these replication results and the prior genomewide association data yielded a genetic dataset derived from 1,351 PBC cases and 4,700 controls. Hirschfield et al. (2010) identified association with PBC at a region on chromosome 17q12-q21 represented by SNP rs11557467 in the ZPBP2 gene (608499) (combined p = 3.5 x 10(-13), OR = 0.72).
Description Primary biliary cirrhosis (PBC) is a chronic, progressive cholestatic liver disease that usually affects middle-aged women and eventually leads to liver failure (summary by Kaplan, 1996). For a discussion of genetic heterogeneity of primary biliary cirrhosis (PBC), see PBC1 (109720). Mapping In a 2-stage genomewide association study involving a total of 536 patients with primary biliary cirrhosis and 1,536 controls, Hirschfield et al. (2009) found significant association between PBC and 13 loci across the HLA class II region on chromosome 6p21.3, with HLA-DQB1 (604305) having the strongest association (combined p for rs2856683 = 1.78 x 10(-19); odds ratio, 1.75).
Description Primary biliary cirrhosis (PBC) is a chronic, progressive cholestatic liver disease that usually affects middle-aged women and eventually leads to liver failure (summary by Kaplan, 1996). For a discussion of genetic heterogeneity of primary biliary cirrhosis (PBC), see PBC1 (109720). Mapping In a 2-stage genomewide association study involving a total of 536 patients with primary biliary cirrhosis and 1,536 controls, Hirschfield et al. (2009) found significant association between PBC and rs3790567 at the IL12RB2 locus (601642) on chromosome 1p31.2 (combined p = 2.76 x 10(-11); odds ratio, 1.51).
Significant association of PBC has also been shown with SNPs at the HLA-DQB1 locus (604305) on chromosome 6p21.3 (PBC2; 613007), at the IL12RB2 locus (601642) on chromosome 1p31.2 (PBC3; 613008), at the IRF5 (607218)-TNPO3 (610032) locus on chromosome 7q32 (PBC4; 614220), and at the ZPBP2 locus (608499) on chromosome 17q12-q21 (PBC5; 614221). See also Reynolds syndrome (613471), in which primary biliary cirrhosis is a feature. ... Hirakata et al. (1988) described 2 unrelated patients with a combination of the CREST syndrome (181750) and primary biliary cirrhosis.
Primary biliary cholangitis is associated with metabolic or immune system disorders, including thyroid problems, limited scleroderma (CREST syndrome), rheumatoid arthritis, and dry eyes and mouth (Sjogren's syndrome).
Primary biliary cholangitis (PBC) is a chronic, progressive liver disease in which the bile ducts become inflamed and damaged. This leads to the buildup of bile and causes liver problems such as scarring, cirrhosis (scarring and poor liver function), and eventual liver failure . PBC is more common in women. Many people do not have symptoms when they are first diagnosed and may not develop symptoms for several years. Early symptoms may include fatigue (the most common symptom), itchy skin ( pruritus ), and abdominal pain. As the disease progresses, people with PBC may develop weakness, nausea, diarrhea, swelling in the legs and feet (edema), bone and joint pain, jaundice, dark urine, and xanthomas .
Description Primary biliary cirrhosis (PBC) is a chronic, progressive cholestatic liver disease that usually affects middle-aged women and eventually leads to liver failure (summary by Kaplan, 1996). For a discussion of genetic heterogeneity of primary biliary cirrhosis (PBC), see PBC1 (109720). Mapping To replicate the findings of Hirschfield et al. (2009) and to evaluate the relevance of identified loci to PBC susceptibility, Hirschfield et al. (2010) tested an additional independent cohort of 857 individuals with PBC and 3,198 controls, all of European descent, for PBC associations with 36 SNPs across 24 loci. The combination of these replication results and the prior genomewide association data yielded a genetic dataset derived from 1,351 PBC cases and 4,700 controls. The locus on chromosome 7q32 near the IRF5 (607218)-TNPO3 (610032) genes was confirmed by this analysis (SNP rs10488631, replication dataset p = 1.13 x 10(-8), OR = 1.58; combined dataset p = 8.66 x 10(-13), OR = 1.57).
Neurodegenerative diseases including Parkinson's disease and “Parkinson’s Plus diseases” including multiple system atrophy and Lewy body dementia , and multiple sclerosis Autonomic neuropathy may also be caused by an abnormal attack by the immune system ( autoimmune autonomic ganglionopathy ), sometimes as part of a paraneoplastic syndrome which can occur even when cancer has not yet been diagnosed. ... Autoimmune diseases , in which the immune system attacks and damages parts of the body, including the nerves. Examples include Sjögren syndrome , systemic lupus erythematosus , rheumatoid arthritis and celiac disease . Guillain–Barré syndrome is an autoimmune disease that happens rapidly and can affect autonomic nerves.
Autoimmune diseases, in which your immune system attacks and damages parts of your body, including your nerves. Examples include Sjogren syndrome, systemic lupus erythematosus, rheumatoid arthritis and celiac disease. Guillain-Barre syndrome is an autoimmune disease that happens rapidly and can affect autonomic nerves. Autonomic neuropathy may also be caused by an immune system attack triggered by some cancers (paraneoplastic syndrome). Certain medications, including some drugs used in cancer treatment (chemotherapy).
MRI showed bilateral lesions within the brain consistent with Leigh syndrome (see 256000). He developed an abnormal breathing pattern and died at age 14 months. ... The former patient had a severe presentation consistent with Leigh syndrome (see 256000) and early death. The latter patient had developmental delay and myoclonic epilepsy. ... INHERITANCE - X-linked recessive HEAD & NECK Eyes - Nystagmus RESPIRATORY - Abnormal breathing pattern (in some patients) MUSCLE, SOFT TISSUES - Axial hypotonia NEUROLOGIC Central Nervous System - Global developmental delay - Delayed language - Delayed walking - Choreoathetosis - Extrapyramidal signs - Myoclonic seizures - White matter abnormalities consistent with Leigh syndrome seen on brain imaging (in some patients) - Cerebellar atrophy (in some patients) Peripheral Nervous System - Hyporeflexia LABORATORY ABNORMALITIES - Increased serum lactate (in some patients) - Mitochondrial respiratory complex I deficiency in various tissues MISCELLANEOUS - Onset in the first year of life - Variable severity - Death in early childhood may occur - Two unrelated families have been reported (last curated January 2019) MOLECULAR BASIS - Caused by mutation in the NADH-ubiquinone oxidoreductase subunit A gene (NDUFA1, 300078.0001 ) ▲ Close
A form of cutaneous lupus erythematosus (CLE) that can present either as a non-scarring, annular photo-distributed dermatosis or psoriasiform plaques. This disorder is associated with anti-Ro/SSA antibodies and can be drug-induced.
Congenital chloride diarrhea Other names Darrow Gamble syndrome This condition is inherited via autosomal recessive manner Congenital chloride diarrhea ( CCD , also congenital chloridorrhea or Darrow Gamble syndrome ) is a genetic disorder due to an autosomal recessive mutation on chromosome 7 . ... Diastrophic dysplasia , congenital chloride diarrhea, and Pendred syndrome are caused by the highly related genes SLC26A2 (first called DTDST), SLC26A3 (first called CLD or DRA), and SLC26A4 (first called PDS), respectively. [9] Two of these diseases, diastrophic dysplasia and congenital chloride diarrhea, are Finnish heritage diseases . [ citation needed ] References [ edit ] ^ Dorwart MR, Shcheynikov N, Yang D, Muallem S (April 2008).
Congenital chloride diarrhea (CCD) is a lifelong condition that causes large, watery stools (diarrhea) that contain an excess of chloride. Those with CCD have diarrhea even before birth. Signs of CCD before birth may be detected with an ultrasound, and may include an increased amount of amniotic fluid (polyhydramnios) and enlarged (dilated) intestinal loops in the fetus. Newborns with CCD are often premature and may have a swollen-looking abdomen ( abdominal distention ). For this reason, CCD is sometimes first mistaken for an intestinal obstruction. CCD causes electrolyte imbalances including low blood sodium levels ( hyponatremia ) and chloride levels (hypochloremia).
The electrolyte disorder resembles the renal disorder Bartter syndrome (see 607364), except that chloride diarrhea is not associated with calcium level abnormalities (summary by Choi et al., 2009). ... In chloride diarrhea, juxtaglomerular hyperplasia, hyperreninemia and hyperaldosteronism, leading to hyperkaluria and hypokalemia, simulate the Bartter syndrome (see 241200). As in the latter disorder, inhibitors of prostaglandin synthetase have beneficial effects (Minford and Barr, 1980). ... Choi et al. (2009) used whole-exome capture and massively parallel DNA sequencing to identify a homozygous pathogenic mutation in the SLC26A3 gene in a Turkish infant with congenital chloride diarrhea who was initially thought to have renal Bartter syndrome. Sequencing this gene in 39 additional patients referred with a suspected diagnosis of Bartter syndrome identified recessive SLC26A3 mutations in 5 patients. ... INHERITANCE - Autosomal recessive GROWTH Other - Failure to thrive - Poor growth CARDIOVASCULAR Vascular - Hypotension due to volume depletion ABDOMEN External Features - Abdominal distention Gastrointestinal - Diarrhea, watery - Diarrhea contains high chloride levels GENITOURINARY Kidneys - Juxtaglomerular hyperplasia due to activation of the renin-aldosterone axis METABOLIC FEATURES - Dehydration - Metabolic alkalosis PRENATAL MANIFESTATIONS Amniotic Fluid - Polyhydramnios Delivery - Premature birth LABORATORY ABNORMALITIES - Hypokalemia - Hyponatremia - Hypochloremia - Increased serum bicarbonate - Increased aldosterone - Increased plasma renin activity MISCELLANEOUS - Onset in first weeks to months of life - Chronic disorder - Electrolyte imbalances can mimic renal Bartter syndrome ( 601678 ) MOLECULAR BASIS - Caused by mutation in the solute carrier family 26, member 3 gene (SLC26A3, 126650.0001 ) ▲ Close
A rare genetic intestinal disease characterized by persistent, potentially life-threatening, watery diarrhea with excessive levels of chloride in stools, hypochloremia, hyponatremia, hypokalemia, and metabolic alkalosis, resulting in chronic dehydration and failure to thrive. Antenatal ultrasound typically reveals polyhydramnios and significant dilatation of the fetal intestinal loops.
Left ventricular noncompaction can also be part of syndromes that affect multiple parts of the body. When left ventricular noncompaction is part of a syndrome, it is caused by mutations in the gene that cause that syndrome.
Nodal marginal zone B-cell lymphoma is a rare, indolent B-cell non-Hodgkin lymphoma, characterized by abnormal clonal proliferation of mature B-lymphocytes with involvement of the lymph nodes, sometimes the bone marrow, and rarely the blood. Clinically it presents with disseminated peripheral, abdominal and/or thoracic lymphadenopathy. Cytopenia and bulky tumors (greater than 5 cm) are rare. Association with Hepatitis C virus and chronic inflammation has been reported.
Clinical Features Among the children of a consanguineous mating, Mutchinick (1972) described 2 with an apparently distinctive syndrome of mental and physical retardation, peculiar facies, and heart and renal malformations. ... Tonoki et al. (1999) described a Japanese girl with Mutchinick syndrome, indicating that it is not restricted to descendants of individuals from East Prussia.
Molecular Genetics Berry aneurysm may have an increased frequency in persons with Ehlers-Danlos syndrome type IV (130050), which is caused by mutation in the type III collagen gene (COL3A1; 120180) on chromosome 2q. ... De Paepe et al. (1988) proposed that a defect in type III collagen may be responsible for familial multiple intracranial aneurysms, perhaps with few signs suggesting Ehlers-Danlos syndrome type IV. The same suggestion had been made by Pope et al. (1981).
Although the radiographic and chondroosseous morphologic findings in these sibs bore certain similarities to Dyggve-Melchior-Clausen syndrome (223800), their clinical course did not fit that condition. Thus, Khosravi et al. (1998) suggested that they represent a new syndrome of bone dysplasia and CNS degeneration inherited as an autosomal recessive.
Etiology Secondary ATM may also occur as a result of direct bacterial, parasitic or viral invasion of the spinal cord, and in patients with Sjögren's syndrome (see this term). Diagnostic methods Diagnosis requires MRI of the spinal cord to confirm the presence of myelitis: for example, long lesions in patients with NMO, short and multifocal lesions in patients with MS. Laboratory tests are also essential for identifying the cause of secondary ATM: analysis of the cerebrospinal fluid may reveal the presence of oligoclonal bands (commonly seen in MS) or bacterial/viral/parasitic infections; serology may reveal the presence of autoantibodies to aquaporin-4 (NMO), anti-double-stranded DNA antibodies (SLE) or anti-Ro/SS-A antibodies (Sjögren's syndrome). Visual evoked responses may be abnormal.
Andres et al. (1981) presented a family with the trait in multiple sibships of 3 generations with male-to-male transmission. The authors suspected a syndromal relationship to deafness in their family. ... None had manifestations of the velocardiofacial syndrome (192430). Kannu et al. (2003) reported a family in which father-to-son transmission demonstrated autosomal dominant inheritance of velopharyngeal insufficiency.
These symptoms may be the expression of hyperviscosity syndrome due to high levels of monoclonal cryoglobulins. ... Management and treatment Plasma exchange treatment, with/without steroids and/or immunosuppressors, is beneficial for simple cryoglobulinemia patients presenting with clinically overt hyperviscosity syndrome. In patients with malignant B-cell neoplasias, the chemotherapy may lead to resolution of this serological manifestation.
Differential diagnosis Differential diagnoses include other conditions that manifest with hypotransferrinemia such as GRACILE syndrome and nephrotic syndromes (see these terms) and, in adults, those suffering from chronic alcoholism.
A number sign (#) is used with this entry because atransferrinemia is caused by homozygous or compound heterozygous mutation in the structural gene for transferrin (TF; 190000) on chromosome 3q22. Variation in the TF gene also affects serum transferrin levels. Variation in the HFE gene (613609.0001) also affects serum transferrin levels (see TFQTL2, 614193). Description Atransferrinemia is characterized by microcytic anemia and by iron loading. It can be treated effectively by plasma infusions (summary by Beutler et al., 2000). Clinical Features Heilmeyer et al. (1961) described total absence of transferrin in a 7-year-old girl whose presenting complaint was severe hypochromic anemia.
Trisomy 10p is a syndrome of mental retardation/multiple congenital malformations (MR-MCA) that is caused by the total or partial duplication of the short arm of chromosome 10. ... Differential diagnosis Differential diagnoses include other syndromes of developmental delay with dysmorphism and congenital malformations.
Chromosome 10p duplication is a chromosome abnormality that occurs when there is an extra copy of genetic material on the short arm (p) of chromosome 10 . The severity and the signs and symptoms depend on the size and location of the duplication and which genes are involved. The size of the duplication can range from a tiny piece of the chromosome arm, to the entire arm. Signs and symptoms that can be present in a person with a 10p duplication may include delay of development, motor skills, or growth; short stature; low muscle tone (hypotonia); abnormalities of the foot (such as clubfoot ); cleft lip and/or cleft palate; and distinctive facial features. Other signs and symptoms may include seizures, a heart defect, or other birth defects.
Clinical description Patients can be asymptomatic but more often present with chest-related symptoms (cough, chest pain), phrenic nerve palsy, or superior vena cava syndrome. Contrary to patients with thymoma (see this term), myasthenia gravis or paraneoplastic syndromes are rarely observed.
Differential diagnosis Differential diagnoses for hereditary thrombocytopenia with normal platelets-hematological cancer predisposition syndrome include several inherited disorders such as Congenital amegakaryocytic thrombocytopenia (CAMT), thrombocytopenia with absent radii (TAR), and Wiskott-Aldrich syndrome (WAS).
They described an Italian family with 3 members affected with FPD/AML, 2 sibs and their father, who developed myelodysplastic syndromes, which in one subsequently evolved into AML.