True ageusia is relatively rare compared to hypogeusia – a partial loss of taste – and dysgeusia – a distortion or alteration of taste. [1] [2] Contents 1 Causes 1.1 Neurological damage 1.2 Problems with the endocrine system 1.3 Other causes 2 Diagnosis 3 References 4 External links Causes [ edit ] The main causes of taste disorders are head trauma, infections of upper respiratory tract, exposure to toxic substances, iatrogenic causes, medicines, glossodynia (" burning mouth syndrome (BMS)") [2] and COVID-19 . [3] Head trauma can cause lesions in regions of the central nervous system which are involved in processing taste stimuli, including thalamus , brain stem , and temporal lobes ; it can also cause damage to neurological pathways involved in transmission of taste stimuli. [ citation needed ] Neurological damage [ edit ] Tissue damage to the nerves that support the tongue can cause ageusia, especially damage to the chorda tympani nerve and the glossopharyngeal nerve . ... Disorders of the endocrine system, such as Cushing's syndrome , hypothyroidism and diabetes mellitus , can cause similar problems.
This article needs more medical references for verification or relies too heavily on primary sources . Please review the contents of the article and add the appropriate references if you can. Unsourced or poorly sourced material may be challenged and removed . Find sources: "Hypogeusia" – news · newspapers · books · scholar · JSTOR ( September 2019 ) Hypogeusia Differential diagnosis zinc deficiency Hypogeusia is a reduced ability to taste things (to taste sweet, sour, bitter, or salty substances). The complete lack of taste is referred to as ageusia . Causes of hypogeusia include the chemotherapy drug bleomycin , an antitumor antibiotic as well as zinc deficiency. [ citation needed ] References [ edit ] v t e Symptoms and signs relating to perception , emotion and behaviour Cognition Confusion Delirium Psychosis Delusion Amnesia Anterograde amnesia Retrograde amnesia Convulsion Dizziness Disequilibrium Presyncope / Lightheadedness Vertigo Emotion Anger Anxiety Depression Fear Paranoia Hostility Irritability Suicidal ideation Behavior Verbosity Russell's sign Perception Sensory processing disorder Hallucination ( Auditory hallucination ) Smell Anosmia Hyposmia Dysosmia Parosmia Phantosmia Hyperosmia Synesthesia Taste Ageusia Hypogeusia Dysgeusia Hypergeusia This medical symptom article is a stub . You can help Wikipedia by expanding it . v t e
A number sign (#) is used with this entry because of evidence that progressive familial intrahepatic cholestasis-3 (PFIC3) is caused by mutation in the gene encoding the class III multidrug resistance (MDR3) P-glycoprotein (ABCB4; 171060). For a general phenotypic description and a discussion of genetic heterogeneity of PFIC, see PFIC1 (211600). Clinical Features De Vree et al. (1998) reported 2 unrelated patients with PFIC3. The first patient was a Turkish boy, born of consanguineous parents, who had recurrent bouts of jaundice from the age of 3 months, when he presented with severe icterus, diarrhea, fever, and pruritus. At the age of 3 years, he showed hepatosplenomegaly, elevated serum liver enzymes, increased gamma-glutamyltransferase (GGT1; 612346) activity (6 times normal), and a high serum bile acid concentration (50 times normal).
Progressive familial intrahepatic cholestasis (PFIC) refers to a heterogeneous group of autosomal recessive disorders of childhood that disrupt bile formation and present with cholestasis of hepatocellular origin. Epidemiology The exact prevalence remains unknown, but the estimated prevalence at birth varies between 1/50,000 and 1/100,000. Clinical description Three types of PFIC have been identified and are related to mutations in hepatocellular transport system genes involved in bile formation. PFIC1 and PFIC2 (see these terms) usually appear in the first months of life, whereas onset of PFIC3 (see this term) may also occur later in infancy, in childhood or even during young adulthood. Main clinical manifestations include cholestasis, pruritus and jaundice.
A number sign (#) is used with this entry because progressive familial intrahepatic cholestasis-4 (PFIC4) is caused by homozygous or compound heterozygous mutation in the TJP2 gene (607709) on chromosome 9q21. For a phenotypic description and a discussion of genetic heterogeneity of progressive familial intrahepatic cholestasis, see PFIC1 (211600). Clinical Features Sambrotta et al. (2014) reported 12 patients from 8 families with early childhood onset of severe progressive liver disease. One child died at age 13 months, 9 patients required a liver transplant, and 2 had stable liver disease with mild portal hypertension at ages 4 and 7 years, respectively. Laboratory studies showed normal or mildly increased GGT levels. No additional clinical details were given.
A number sign (#) is used with this entry because progressive familial intrahepatic cholestasis-1 (PFIC1) is caused by homozygous or compound heterozygous mutation in the ATP8B1 gene (602397) on chromosome 18q21. Mutation in the ATP8B1 gene can also cause benign recurrent intrahepatic cholestasis-1 (BRIC1; 243300) and intrahepatic cholestasis of pregnancy-1 (ICP1; 147480). Description 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 Cholestasis PFIC is a genetically heterogeneous disorder caused by defects in the transport of bile acids. See also PFIC2 (601847), caused by mutation in a liver-specific ATP-binding cassette transporter gene (ABCB11; 603201) on chromosome 2q24; PFIC3 (602347), caused by mutation in the class III multidrug resistance P-glycoprotein gene (ABCB4; 171060) on chromosome 7q21; PFIC4 (615878), caused by mutation in the TJP2 gene (607709) on chromosome 9q12; and PFIC5 (617049), caused by mutation in the NR1H4 gene (603826) on chromosome 12q.
A number sign (#) is used with this entry because of evidence that progressive familial intrahepatic cholestasis-2 (PFIC2) is caused by homozygous or compound heterozygous mutation in the ABCB11 gene (603201), which encodes a liver-specific ATP-binding cassette (ABC) transporter, on chromosome 2q31. Benign recurrent intrahepatic cholestasis-2 (BRIC2; 605479) is an allelic disorder. For a phenotypic description and a discussion of genetic heterogeneity of progressive familial intrahepatic cholestasis, see PFIC1 (211600). Clinical Features Sandor et al. (1976) described brother and sister with 'giant cell hepatitis' in infancy. The male died of a rare primary hepatic cancer; the female died of cirrhosis and hepatic coma.
In the second family, the male proband was diagnosed with isolated LVNC and Wolff-Parkinson-White syndrome (WPW; 194200) on routine physical examination at 13 years of age; his asymptomatic mother was found to have LVNC on echocardiography. ... In the second family, the male proband was diagnosed with isolated LVNC and Wolff-Parkinson-White syndrome (WPW; 194200) on routine physical examination at 13 years of age; his asymptomatic mutation-positive mother was found to have LVNC on echocardiography.
A number sign (#) is used with this entry because of evidence that dilated cardiomyopathy-1NN (CMD1NN) is caused by heterozygous mutation in the RAF1 gene (164760) on chromosome 3p25. For a general phenotypic description and a discussion of genetic heterogeneity of dilated cardiomyopathy, see CMD1A (115200). Clinical Features Dhandapany et al. (2014) reported patients with nonsyndromic dilated cardiomyopathy (CMD) and mutations in the RAF1 gene (see MOLECULAR GENETICS). Of 10 patients in whom age of onset was known, 8 presented in childhood or adolescence. The average age at presentation was 12.6 years, which the authors noted was younger than the approximate average of 20 years associated with CMD caused by sarcomeric gene mutations.
A number sign (#) is used with this entry because of evidence that cardiomyopathy of the dilated (CMD1KK), hypertrophic (CMH22), or restrictive (RCM4) type can be caused by heterozygous mutation in the myopalladin gene (MYPN; 608517) on chromosome 10q21. For a general phenotypic description and a discussion of genetic heterogeneity of dilated cardiomyopathy, see 115200; for hypertrophic cardiomyopathy, see 192600; for familial restrictive cardiomyopathy, see 115210. Clinical Features Duboscq-Bidot et al. (2008) studied 6 patients from 2 families, as well as 2 sporadic patients, with isolated dilated cardiomyopathy due to mutations in the myopalladin gene (see MOLECULAR GENETICS). Mean age at diagnosis was 40 years. Of the 8 patients, 4 had incomplete left bundle branch block (BBB) on electrocardiogram, 1 had complete left BBB, and 1 had right BBB; 3 patients had left ventricular hypertrophy. There were 3 cardiac deaths due to refractory congestive heart failure, at 20, 29, and 55 years of age.
A number sign (#) is used with this entry because of evidence that dilated cardiomyopathy-1X (CMD1X) is caused by compound heterozygous mutation in the gene encoding fukutin (FKTN; 607440) on chromosome 9q31. For a general phenotypic description and a discussion of genetic heterogeneity of dilated cardiomyopathy, see CMD1A (115200). Clinical Features Murakami et al. (2006) described 6 Japanese patients from 4 families with dilated cardiomyopathy and mild or no limb-girdle muscle involvement, normal intelligence, and no history of seizures. One patient died at age 12 years from rapidly progressive CMD, and another underwent cardiac transplantation at age 18 years. Skeletal muscle biopsies from the patients showed minimal dystrophic features but altered glycosylation of alpha-dystroglycan (128239) and reduced laminin (see 150240)-binding ability.
A number sign (#) is used with this entry because of evidence that dilated cardiomyopathy-1CC (CMD1CC) is caused by heterozygous mutation in the nexilin gene (NEXN; 613121) on chromosome 1p31. For a phenotypic description and discussion of genetic heterogeneity in dilated cardiomyopathy, see CMD1A (115200). Clinical Features Hassel et al. (2009) reported 9 patients with CMD due to an NEXN mutation with onset of dilated cardiomyopathy in the fifth or sixth decade of life. The average left ventricular end-diastolic diameter was approximately 69 mm, and average left ventricular ejection fraction was approximately 26%. One patient underwent heart transplantation at age 60 years due to progressive dilated cardiomyopathy.
A number sign (#) is used with this entry because of evidence that dilated cardiomyopathy-1M (CMD1M) is caused by heterozygous mutation in the CSRP3 gene (600824) on chromosome 11p15. One such family has been reported. For a general phenotypic description and a discussion of genetic heterogeneity of dilated cardiomyopathy, see CMD1A (115200). Clinical Features In 10 patients with CMD, Knoll et al. (2002) reported a clinical phenotype that included chamber dilation, thin ventricular walls, decreased contractility and impaired relaxation, and no evidence of hypertrophic cardiomyopathy. The phenotype was considered consistent with Csrp3-deficient mouse heart. Mohapatra et al. (2003) described a 2-year-old girl who died after a 2-day illness, in whom autopsy revealed an enlarged and dilated heart with endocardial fibroelastosis (EFE) of the left ventricle.
A number sign (#) is used with this entry because dilated cardiomyopathy-1V is caused by heterozygous mutation in the PSEN2 gene (600759) on chromosome 1q31-q42. For a general phenotypic description and a discussion of genetic heterogeneity of dilated cardiomyopathy, see CMD1A (115200). Clinical Features Li et al. (2006) described 2 families with dilated cardiomyopathy segregating with mutation in the PSEN2 gene (CMD1V). The mutation was present in heterozygous state. Both were white families. Onset of cardiovascular disease occurred at the age of 48 to 55 years in one family.
A number sign (#) is used with this entry because this form of dilated cardiomyopathy is caused by mutation in the gene encoding metavinculin (VCL; 193065). For a general phenotypic description and a discussion of genetic heterogeneity of dilated cardiomyopathy, see CMD1A (115200). Molecular Genetics Olson et al. (2002) used SSCP to analyze the VCL gene, which maps to chromosome 10q, in 350 unrelated patients with sporadic or familial dilated cardiomyopathy who were negative for mutations in the ACTC (102540) and TPM1 (191010) genes, and identified heterozygosity for a 3-bp in-frame deletion (L954del; 193065.0001) and a missense mutation (R975W; 193065.0002) in 2 patients, respectively. Neither mutation was found in 500 controls. A potential risk-conferring polymorphism, A934V, was identified in heterozygosity in a 30-year-old man with dilated cardiomyopathy who died 2 years after diagnosis of progressive heart failure; this variant was also found in 1 of 500 controls, a 67-year-old woman in whom electrocardiography showed abnormal T waves but echocardiogram was nondiagnostic for dilated cardiomyopathy. All 3 variants were located in exon 19, the metavinculin-specific exon of the VCL gene.
A number sign (#) is used with this entry because of evidence that dilated cardiomyopathy-1JJ (CMD1JJ) is caused by heterozygous mutation in the LAMA4 gene (600133) on chromosome 6q21. For a general phenotypic description and a discussion of genetic heterogeneity of dilated cardiomyopathy, see CMD1A (115200). Molecular Genetics Knoll et al. (2007) sequenced the LAMA4 gene in 180 Caucasian patients with severe dilated cardiomyopathy (CMD) and identified heterozygosity for a nonsense (R1073X; 600133.0001) and a missense (P943L; 600133.0002) mutation in 2 patients, respectively. Genotyping for these mutations in an additional 374 Caucasian CMD patients identified 1 more patient with the P943L mutation. Neither mutation was found in 362 well-characterized Caucasian controls, and screening the LAMA4 gene by SSCP in an additional 200 Japanese CMD patients revealed no variants.
A number sign (#) is used with this entry because this form of cardiomyopathy can be caused by mutation in the ABCC9 gene (601439). For a general phenotypic description and a discussion of genetic heterogeneity of dilated cardiomyopathy, see CMD1A (115200). Bienengraeber et al. (2004) performed mutation scans of K(ATP) (ATP-sensitive potassium) channel genes in 323 individuals, predominantly of European descent, with idiopathic dilated cardiomyopathy. They identified 2 heterozygous mutations in the ABCC9 gene, both in exon 38, which encodes the C-terminal domain of SUR2A specific to the cardiac splice variant of the regulatory K(ATP) channel subunit. Both individuals with mutations in ABCC9 had severely dilated hearts with compromised contractile function and rhythm disturbances.
A number sign (#) is used with this entry because of evidence that cardiomyopathy of the dilated (CMD1AA) or hypertrophic (CMH23) type, with or without left ventricular noncompaction (LVNC), can be caused by heterozygous mutation in the gene encoding alpha-actinin-2 (ACTN2; 102573) on chromosome 1q43. For a general phenotypic description and a discussion of genetic heterogeneity of dilated cardiomyopathy, see CMD1A (115200). For a general phenotypic description and a discussion of genetic heterogeneity of hypertrophic cardiomyopathy, see CMH1 (192600). Clinical Features Mohapatra et al. (2003) reported a 7-year-old girl who died of dilated cardiomyopathy only a few weeks after the onset of symptoms. At autopsy, marked dilation of both ventricles, myocyte hypertrophy, and interstitial fibrosis were noted; there were no viral genomic sequences on PCR analysis of cardiac tissue or histologic evidence of myocarditis.
A number sign (#) is used with this entry because of evidence that susceptibility to dilated cardiomyopathy is associated with variation in the desmoglein-2 gene (DSG2; 125671). For a phenotypic description and discussion of genetic heterogeneity in dilated cardiomyopathy, see CMD1A (115200). Molecular Genetics In a man with dilated cardiomyopathy who had severely decreased cardiac function and underwent cardiac transplantation at 44 years of age, Posch et al. (2008) identified homozygosity for the V55M mutation in the DSG2 gene (125671.0009). The proband's father, who had less severe disease with a later onset, was heterozygous for the mutation, as was his asymptomatic mother; his paternal grandfather had died of heart failure at 57 years of age. The proband had no abnormalities of skin or hair. Posch et al. (2008) subsequently screened 538 CMD patients for the DSG2 V55M variant and identified 13 unrelated carriers (2.4%); the variant was also found in 1 (0.23%) of 432 individuals without CMD (p less than 0.006).
A number sign (#) is used with this entry because of evidence that dilated cardiomyopathy-1P (CMD1P) is caused by heterozygous mutation in the phospholamban gene (PLN; 172405) on chromosome 6q22. For a discussion of the genetic heterogeneity in hereditary dilated cardiomyopathy, see CMD1A (115200). Clinical Features Schmitt et al. (2003) reported a 4-generation family with dilated cardiomyopathy (CMD) and heart failure inherited in an autosomal dominant fashion. Affected individuals had increased chamber dimensions and decreased contractile function at age 20 to 30 years, with progression to heart failure within 5 to 10 years after symptom onset. Congestive heart failure was severe in 12 individuals, necessitating cardiac transplantation in 4.
Brain MRI was performed in 2 patients and showed no evidence of focal lesions in the basal ganglia, gray matter, cortex, or brain stem, ruling out Leigh syndrome (256000). Mitochondrial respiratory chain enzymes were assessed in biopsies taken immediately postmortem from 3 patients, and showed moderately reduced activity of complex II in skeletal muscle (50 to 60% residual activity) with marked reduction of activity in cardiac muscle (15 to 18% residual activity).
A number sign (#) is used with this entry because of evidence that left ventricular noncompaction-8 (LVNC8) and dilated cardiomyopathy-1LL (CMD1LL) are caused by heterozygous mutation in the PRDM16 gene (605557) on chromosome 1p36. For a general phenotypic description and a discussion of genetic heterogeneity of left ventricular noncompaction, see LVNC1 (604169). For a general phenotypic description and a discussion of genetic heterogeneity of dilated cardiomyopathy, see CMD1A (115200). Clinical Features Arndt et al. (2013) described 3 patients with left ventricular noncompaction who were found to have mutations in the PRDM16 gene (see MOLECULAR GENETICS). The first patient was a man who presented at 33 years of age with severe biventricular heart failure with systolic and diastolic dysfunction, secondary pulmonary hypertension, and dilation of both atria and ventricles.
A number sign (#) is used with this entry because of evidence that dilated cardiomyopathy-1II (CMD1II) is caused by heterozygous mutation in the CRYAB gene (123590) on chromosome 11q23. Clinical Features Inagaki et al. (2006) studied a 71-year-old Japanese woman with mild, late-onset dilated cardiomyopathy (CMD) who developed cardiac symptoms only after the fourth decade of life. Her electrocardiogram (ECG) showed ventricular tachycardia, with apparent inverted T waves in leads V4 to V6. She had 6 sibs, 2 of whom had CMD at ages 56 and 66 years; 2 other sibs had sudden cardiac death at ages 60 and 72 years. Pilotto et al. (2006) reported a 48-year-old woman with mild, late-onset CMD, characterized by mild left ventricular dilation, moderately decreased ejection fraction, mild mitral regurgitation, and mildly increased serum CPK (279 U/l).
A number sign (#) is used with this entry because of evidence that dilated cardiomyopathy-1HH is caused by heterozygous mutation in the BAG3 gene (603883) on chromosome 10q26.11. For a general phenotypic description and a discussion of genetic heterogeneity of dilated cardiomyopathy (CMD), see CMD1A (115200). Clinical Features Norton et al. (2011) reported 17 individuals from 8 families with dilated cardiomyopathy who carried heterozygous mutations in the BAG3 gene. The age at onset or diagnosis of the CMD phenotype ranged from 21 years to 64 years (median, 44). Disease severity varied considerably: although 9 of the 17 mutation carriers with CMD underwent heart transplant or died with advanced heart failure, there were 4 mutation carriers who had no disease and 1 who was asymptomatic with only mild left ventricular dysfunction.
A number sign (#) is used with this entry because of evidence that dilated cardiomyopathy-2A (CMD2A) is caused by homozygous mutation in the gene encoding cardiac troponin I (TNNI3; 191044) on chromosome 19q13. One such family has been reported. For a general phenotypic description and a discussion of genetic heterogeneity of dilated cardiomyopathy, see 115200. Clinical Features Goldblatt et al. (1987) described 3 members of a Madeira Portuguese family with dilated cardiomyopathy. The first patient presented at age 11 years with dyspnea and congestive heart failure and died 10 weeks later. A cousin was discovered to have cardiac abnormality on routine employment examination at age 20 years and died 14 months later in congestive heart failure.
A number sign (#) is used with this entry because this form of dilated cardiomyopathy (CMD1I) is caused by heterozygous mutation in the DES gene (125660), which encodes desmin, on chromosome 2q35. One such family has been reported. For a general phenotypic description and a discussion of genetic heterogeneity of dilated cardiomyopathy, see CMD1A (115200). Clinical Features Li et al. (1999) studied a 4-generation Caucasian family segregating autosomal dominant dilated cardiomyopathy. The proband had had cardiomegaly and chronic cardiac failure for more than 5 years, with a left ventricular ejection fraction of 40% and diffuse hypokinesis. His son had cardiomegaly with a left ventricular ejection fraction of 45%.
A number sign (#) is used with this entry because of evidence that autosomal dominant dilated cardiomyopathy-1G (CMD1G) is caused by heterozygous mutation in the titin gene (TTN; 188840) on chromosome 2q31. For a general phenotypic description and a discussion of genetic heterogeneity of dilated cardiomyopathy (CMD), see CMD1A (115200). Mapping Siu et al. (1999) clinically evaluated 3 generations of a Native American kindred with autosomal dominant transmission of dilated cardiomyopathy. Nine surviving affected individuals had early-onset disease (ventricular chamber dilatation during the teenage years and congestive heart failure during the third decade of life). The disease was nonpenetrant in 2 obligate carriers. By linkage analysis, Siu et al. (1999) identified a novel disease locus at marker D2S1244 on 2q31 (maximum lod = 4.06 at theta = 0.0) between the glucagon gene (138030) and marker D2S72; they designated this locus CMD1G.
An X-linked form previously designated CMD3A was found to be the same as Barth syndrome (302060). Clinical Features Dilated cardiomyopathy, a disorder characterized by cardiac dilation and reduced systolic function, represents an outcome of a heterogeneous group of inherited and acquired disorders.
For a general phenotypic description and a discussion of genetic heterogeneity of dilated cardiomyopathy, see CMD1A (115200). Clinical Features Jung et al. (1999) studied a German family in which 12 individuals had autosomal dominant CMD characterized by ventricular dilatation, impaired systolic function, and conduction disease. Mapping After exclusion of the known loci for CMD in a German family segregating for the disorder, Jung et al. (1999) performed a whole-genome screen and detected linkage to 2q14-q22. A peak lod score of 3.73 at a recombination fraction of zero was found at D2S2339.
A number sign (#) is used with this entry because of evidence that left ventricular noncompaction-10 (LVNC10) and dilated cardiomyopathy-1MM (CMD1MM) are caused by heterozygous mutation in the MYBPC3 gene (600958) on chromosome 11p11. Clinical Features Probst et al. (2011) described 2 families with left ventricular noncompaction (LVNC) due to mutations in the MYBPC3 gene (see MOLECULAR GENETICS). In the first family, the male proband presented at age 70 years with dyspnea; family screening revealed that his asymptomatic son was also affected. Both patients had noncompacted segments of the left midventricular inferior and lateral wall. In the second family, the female proband had nonsustained ventricular flutter and received an implantable cardioverter-defibrillator; she had noncompacted segments of the apex and midventricular wall.
A number sign (#) is used with this entry because dilated cardiomyopathy-1U is caused by heterozygous mutation in the PSEN1 gene (104311) on chromosome 14q24.3. For a general phenotypic description and a discussion of genetic heterogeneity of dilated cardiomyopathy, see CMD1A (115200). Clinical Features Li et al. (2006) described an African American family with dilated cardiomyopathy segregating with mutation in the PSEN1 gene (CMD1U). Affected members were identified in 3 generations. Onset of dilated cardiomyopathy and heart failure ranged from age 24 to 69 years. Mortality from progressive heart failure usually followed within a few years of diagnosis.
For a general phenotypic description and a discussion of genetic heterogeneity of dilated cardiomyopathy, see CMD1A (115200). Mapping Sylvius et al. (2001) reported the results of a linkage analysis of a French family in which 9 individuals in 3 successive generations expressed the pure form of dilated cardiomyopathy. They identified a novel locus, CMD1K, on 6q12-q16 using a genomewide search after exclusion of all other disease loci and genes for dilated cardiomyopathy. The maximum pairwise lod score was 3.52 at recombination fraction 0.0 for markers D6S1644 and D6S1694. The CMD1K locus did not overlap with 2 other disease loci mapped to 6q, CMD1J (605362) on 6q23-q24, and MFM1 (formerly CMD1F; 601419) on 6q23.
A number sign (#) is used with this entry because dilated cardiomyopathy-1Z is caused by mutation in the gene encoding slow troponin-C (TNNC1; 191040) on chromosome 3p. For a general phenotypic description and a discussion of genetic heterogeneity of dilated cardiomyopathy, see CMD1A (115200). Clinical Features Mogensen et al. (2004) studied a 3-generation family with severe dilated cardiomyopathy in which the proband had sudden onset of heart failure at 21 years of age and underwent cardiac transplantation 2 months later. His mother died at 45 years of age awaiting cardiac transplantation, his maternal grandfather died of heart failure at 62 years of age after 8 months of medical treatment, and a maternal aunt had unexplained sudden death at 21 years of age. A maternal uncle and cousin received cardiac transplants at age 52 and 22 years, respectively; the uncle, who had normal cardiac function at the time of his son's transplant, developed heart failure 2 years later and required transplantation within 2 months of symptom onset.
A number sign (#) is used with this entry because of evidence that dilated cardiomyopathy-2C (CMD2C) is caused by homozygous or compound heterozygous mutation in the PPCS gene (609853) on chromosome 1p34. Description CMD2C is characterized by dilated cardiomyopathy of variable severity, with age of onset ranging from 2 to 20 years. Affected individuals exhibit reduction in coenzyme A (CoA) levels. Some severely affected children die in the first few years of life (Iuso et al., 2018). For a general phenotypic description and a discussion of genetic heterogeneity of dilated cardiomyopathy (CMD), see 115200. Clinical Features Iuso et al. (2018) studied a consanguineous Arab Muslim family (family B) in which 4 sibs had dilated cardiomyopathy of variable severity.
A number sign (#) is used with this entry because dilated cardiomyopathy-1S (CMD1S) is caused by heterozygous mutation in the MYH7 gene (160760) on chromosome 14q12. Mutation in the MYH7 gene has also been associated with left ventricular noncompaction (LVNC5), hypertrophic cardiomyopathy (CMH1; 192600), and myosin storage myopathy (608358). For a general phenotypic description and a discussion of genetic heterogeneity of dilated cardiomyopathy, see CMD1A (115200); for a similar discussion of left ventricular noncompaction, see LVNC1 (604169). Clinical Features Kamisago et al. (2000) studied affected members of a large 4-generation family segregating autosomal dominant dilated cardiomyopathy (CMD). Seventeen family members had dilated cardiomyopathy without conduction system disease, skeletal muscle dysfunction, or other phenotypes.
A number sign (#) is used with this entry because this form of dilated cardiomyopathy (CMD1R) is caused by heterozygous mutation in the ACTC1 gene (102540) on chromosome 15q14. Mutation in the ACTC1 gene has also been associated with left ventricular noncompaction (LVNC4), hypertrophic cardiomyopathy (CMH11; 612098), and atrial septal defects (ASD5; 612794). For a general phenotypic description and a discussion of genetic heterogeneity of dilated cardiomyopathy, see CMD1A (115200); for a similar discussion of left ventricular noncompaction, see LVNC1 (604169). Clinical Features Olson et al. (1998) studied 2 unrelated families with autosomal dominant idiopathic dilated cardiomyopathy (CMD), one of German ancestry and the other of Swedish Norwegian ancestry. Families were phenotypically characterized by echocardiography, with CMD being defined as left ventricular end-diastolic dimension (LVEDD) greater than the 95th percentile for age and body surface area, and shortening fraction less than 28%.
A number sign (#) is used with this entry because of evidence that dilated cardiomyopathy-1DD is caused by heterozygous mutation in the RBM20 gene (613171) on chromosome 10q25. For a general phenotypic description and a discussion of genetic heterogeneity of dilated cardiomyopathy, see CMD1A (115200). Clinical Features Brauch et al. (2009) studied 2 large multigenerational European American families with dilated cardiomyopathy (CMD). In 'kindred DC-12,' the patriarch, who was of Scottish ancestry, died suddenly at 39 years of age. Ten family members developed documented CMD, 2 as young children; the mean age at diagnosis was 30 years.
A number sign (#) is used with this entry because dilated cardiomyopathy-1Y (CMD1Y) and left ventricular noncompaction-9 (LVNC9) are caused by heterozygous mutation in the TPM1 gene (191010) on chromosome 15q22.1. For a general phenotypic description and a discussion of genetic heterogeneity of dilated cardiomyopathy, see CMD1A (115200). Description Dilated cardiomyopathy-1Y (CMD1Y) is characterized by severe progressive cardiac failure, resulting in death in the third to sixth decades of life in some patients. Electron microscopy shows an abnormal sarcomere structure (Olson et al., 2001). In left ventricular noncompaction-9 (LVNC9), patients may present with cardiac failure or may be asymptomatic.
For a general phenotypic description and a discussion of genetic heterogeneity of dilated cardiomyopathy, see CMD1A (115200). Clinical Features Schonberger et al. (2005) reported a 3-generation Portuguese family in which 16 individuals had dilated cardiomyopathy (CMD). The pedigree was consistent with autosomal dominant inheritance and age-related penetrance, with age of onset between 25 and 47 years of age. Mapping In a 3-generation Portuguese family segregating autosomal dominant dilated cardiomyopathy, Schonberger et al. (2005) performed genomewide linkage analysis and excluded linkage to all known CMD genes and loci, whereas several close markers on chromosome 7q22.3-q31.1 segregated with the disease (maximum lod score, 4.20 at D7S471 and D7S501). Recombination events defined a 9.73-Mb disease interval between D7S2545 and D7S2554.
A number sign (#) is used with this entry because this form of dilated cardiomyopathy is caused by mutations in the gene encoding delta-sarcoglycan (SGCD; 601411). Description Dilated cardiomyopathy, a disorder characterized by cardiac dilation and reduced systolic function, represents an outcome of a heterogeneous group of inherited and acquired disorders. For background and phenotypic information on dilated cardiomyopathy, see CMD1A (115200). Molecular Genetics Cardiomyopathy in the hamster is a model of human hereditary cardiomyopathy and is divided into hypertrophic cardiomyopathy (HCM; BIO 14.6 strain) and dilated cardiomyopathy (DCM; TO-2 strain) inbred sublines, both of which descended from the same ancestor and are due to mutations in the gene encoding delta-sarcoglycan (Sakamoto et al., 1997; Nigro et al., 1997). Hypothesizing that DCM is a disease of the cytoskeleton and sarcolemma, Tsubata et al. (2000) focused on candidate genes whose products are found in these structures.
A number sign (#) is used with this entry because familial dilated cardiomyopathy mapping to 1q32 was shown to result from heterozygous mutation in the gene encoding cardiac troponin T (TNNT2; 191045) on chromosome 1q32. Mutation in the TNNT2 gene has also been associated with left ventricular noncompaction (LVNC6), hypertrophic cardiomyopathy (CMH2; 192600), and restrictive cardiomyopathy (RCM3; 612422). For a general phenotypic description and a discussion of genetic heterogeneity of dilated cardiomyopathy, see CMD1A (115200); for a similar discussion of left ventricular noncompaction, see LVNC1 (604169). Clinical Features Kamisago et al. (2000) studied families with dilated cardiomyopathy. In 1 family (family C), sudden death occurred in a 26- and a 27-year-old as well as in a 1- and an 8-month-old, both of whom had a diagnosis of infantile cardiomyopathy.
A number sign (#) is used with this entry because of evidence that dilated cardiomyopathy-1E can be caused by mutation in the cardiac sodium channel gene SCN5A (600163). For a general phenotypic description and a discussion of genetic heterogeneity of dilated cardiomyopathy, see CMD1A (115200). Clinical Features Greenlee et al. (1986) reported a large family of German and Swiss ancestry with dilated cardiomyopathy, conduction defect, and arrhythmia. The phenotype included sinus node dysfunction in adolescence, supraventricular tachyarrhythmia, and progressive atrial ventricular and intraventricular conduction delay that led to permanent pacing in most cases. The phenotype was also characterized by a progression toward atrial dilation, frequently followed by right ventricular dilation and, in some cases, led to ventricular dilation and dysfunction.
For a general phenotypic description and a discussion of genetic heterogeneity of dilated cardiomyopathy, see CMD1A (115200). Mapping In a single large 6-generation family with autosomal dominant dilated cardiomyopathy, Krajinovic et al. (1995) performed a genomewide search for linkage. After a large series of candidate genes were excluded, they demonstrated linkage to 9q13-q22 with a maximum multipoint lod score of 4.2 (when data from 2 other families selected on the basis of the same stringent diagnostic criteria were included). There was no evidence of heterogeneity. The FDC locus was placed in the interval between D9S153 and D9S152. Friedreich ataxia (229300), which is frequently associated with dilated cardiomyopathy, maps to the same region as does also the cAMP-dependent protein kinase (176893), which regulates calcium-channel ion conductance in the heart.
A rare familial cardiomyopathy characterized by the dilation of left ventricle and progressively impairing of systolic ventricular function, in the absence of abnormal loading conditions or coronary artery disease sufficient to cause global systolic impairment. The disease may cause heart failure or arrhythmia. The disease is isolated when no additional atypical cardiac or extracardiac manifestations are present. Epidemiology The prevalence and incidence of Familial isolated dilated cardiomyopathy (FDC) is unknown; however, the incidence of dilated cardiomyopathy (DCM) is estimated between 1/12,000-28,000 worldwide; the prevalence of dilated cardiomyopathy is estimated at 1/2500; FDC is reported to make up about 20-30% of DCM case (range 2-65%). Clinical description The disease is defined by the presence of two major clinical criteria: left ventricular (LV) fractional shortening less than 25% and/or LV ejection fraction less than 45% with LV end diastolic diameter greater than 117% of the predicted value (corrected for age and body surface area based on Henry's formula), in the absence of abnormal loading conditions or coronary artery disease sufficient to cause global systolic impairment. The disease can develop at any age, in either sex. LV mass is often greatly increased in this disorder but LV wall thickness is normal.
A number sign (#) is used with this entry because of evidence that dilated cardiomyopathy-2B (CMD2B) is caused by homozygous mutation in the GATAD1 gene (614518) on chromosome 7q21. One such family has been reported. For a general phenotypic description and a discussion of genetic heterogeneity of dilated cardiomyopathy (CMD), see 115200. Clinical Features Theis et al. (2011) studied a consanguineous family of Norwegian ancestry segregating autosomal recessive dilated cardiomyopathy. The proband was a 74-year-old woman who presented at age 50 with heart failure and cardiomegaly; echocardiography was diagnostic for CMD. Left ventricular endomyocardial biopsy showed moderate myocyte hypertrophy, mild focal interstitial fibrosis, and mild diffuse endocardial fibrosis, consistent with chronic cardiomyopathy.
A number sign (#) is used with this entry because of evidence that dilated cardiomyopathy-1FF is caused by heterozygous mutation in the TNNI3 gene (191044). For a general phenotypic description and discussion of genetic heterogeneity in dilated cardiomyopathy, see CMD1A (115200). Molecular Genetics Carballo et al. (2009) analyzed the TNNI3 gene in 96 probands with dilated cardiomyopathy (CMD) in whom screening for mutations in 6 more commonly implicated CMD genes was negative and identified heterozygosity for 2 different TNNI3 missense mutations in 2 male probands (191044.0012 and 191044.0013, respectively). The probands, who were diagnosed with CMD at ages 15 and 24 years, respectively, both required cardiac transplantation soon after diagnosis.
A number sign (#) is used with this entry because of evidence that this form of dilated cardiomyopathy is caused by mutation in the MYH6 gene (160710). For a general phenotypic description and discussion of genetic heterogeneity in dilated cardiomyopathy, see CMD1A (115200). Molecular Genetics Carniel et al. (2005) analyzed the MYH6 gene in 69 families with dilated cardiomyopathy (CMD), including 134 affected and 214 unaffected individuals, and identified 3 heterozygous missense mutations in 3 sporadic Caucasian patients (160710.0005-160710.0007, respectively). None of the 3 mutations were detected in 150 ethnically similar controls. Mutations in 7 known CMD genes were excluded in the patients in whom MYH6 mutations had been identified.
A number sign (#) is used with this entry because the Silverman-Handmaker type of dyssegmental dysplasia (DDSH) is caused by homozygous or compound heterozygous mutation in the gene encoding perlecan (HSPG2; 142461) on chromosome 1p36. See also Schwartz-Jampel syndrome type 1 (SJS1; 255800), an allelic disorder with a less severe but overlapping phenotype.
Dyssegmental dysplasia, Silverman-Handmaker type is a rare, genetic, primary bone dysplasia disorder, and lethal form of neonatal short-limbed dwarfism, characterized by anisospondyly, severe short stature and limb shortening, metaphyseal flaring and distinct dysmorphic features (i.e. flat facial appearance, abnormal ears, short neck, narrow thorax). Additional features may include other skeletal findings (e.g. joint contractures, bowed limbs, talipes equinovarus) and urogenital and cardiovascular abnormalities.
Pure autosomal dominant cerebellar ataxia is a relatively benign, late-onset, slowly progressive neurologic disorder characterized by an uncomplicated cerebellar syndrome (see SCA1; 164400). For a general discussion of autosomal dominant spinocerebellar ataxia, see SCA1 (164400).
Summary Clinical characteristics. Spinocerebellar ataxia type 11 (SCA11) is characterized by progressive cerebellar ataxia and abnormal eye signs (jerky pursuit, horizontal and vertical nystagmus). Pyramidal features are seen on occasion. Peripheral neuropathy and dystonia are rare. Six families have been reported to date, one each from the UK, Pakistan, France, Germany, Denmark, and China. Age of onset ranged from early childhood to the mid-40s. Life span is thought to be normal. Diagnosis/testing. The diagnosis of spinocerebellar ataxia type 11 (SCA11) is established in a proband with a heterozygous pathogenic variant in TTBK2 identified by molecular genetic testing.
A rare neurologic disease that is characterized by the early-onset of cerebellar signs, eye movement abnormalities and pyramidal signs. Epidemiology Spinocerebellar ataxia type 11 (SCA11) prevalence is unknown but SCA11 is thought to account for 2% of ADCA type III cases. More than sixty clinically affected members from six families (of British, Pakistani, Danish, Chinese, German and French descent) have been reported to date. Clinical description SCA11 presents between the ages of 11-70 years with a mean age of onset of 25 years. It presents with the cerebellar signs such as dysarthria and progressive ataxia, eventually leading to difficulty walking and loss of balance as well as eye movement abnormalities (jerky pursuit, horizontal and vertical nystagmus and ophthalmoplegia).
Spinocerebellar ataxia type 11 (SCA11) is characterized by progressive cerebellar ataxia (difficulty walking and balance) and abnormal eye signs (jerky pursuit, horizontal and vertical movements (nystagmus), pyramidal features (increased muscular tonus, increased reflexes and an abnormal reflex known as Babinski sign and inability to make to perform fine movements), peripheral neuropathy with numbness, weakness or pain in the feet or hands or other places of the body and dystonia. It is a very rare disease and very few patients have been reported to date. Age of onset ranges from the early teens to the mid 20s and life span is normal. Diagnosis is based on signs and symptoms and is confirmed by genetic testing finding a change (mutation) in the TTBK2 gene . It is inherited in an autosomal dominant manner. Treatment may include speech and language therapy for talking and swallowing problems, occupational therapy, including home adaptations, physiotherapy and use of assistive walking devices and ankle-foot orthotics (AFOs) for those with neuropathy.
A number sign (#) is used with this entry because of evidence that a syndrome involving short stature, developmental delay, and congenital heart defects (SDDHD) is caused by homozygous or compound heterozygous mutation in the TKT gene (606781) on chromosome 3p21.
A rare disorder of pentose phosphate metabolism characterized by developmental delay and intellectual disability, delayed or absent speech, short stature, and congenital heart defects (such as ventricular septal defect, atrial septal defect, and patent foramen ovale). Additional reported features include hypotonia, hyperactivity, stereotypic behavior, ophthalmologic abnormalities (bilateral cataract, uveitis, strabismus), hearing impairment, and variable facial dysmorphism, among others. Laboratory analysis shows elevated plasma and urinary polyols (erythritol, arabitol, and ribitol) and urinary sugar-phosphates (ribose-5-phosphate and xylulose/ribulose-5-phosphate).
However, some NETs are associated with a hereditary cancer or tumor syndrome such as multiple endocrine neoplasia type 1 (most commonly), Von Hippel-Lindau disease , tuberous sclerosis , or neurofibromatosis type 1 (NF1).
Mapping In a 4-generation Chinese family segregating autosomal dominant high myopia, Ma et al. (2010) excluded known syndromic myopia loci, and linkage to known loci for nonsyndromic autosomal dominant high myopia was insignificant or suggestive only.
The possibility of a generalized membrane defect was raised. Also, similarities to Lowe syndrome (309000) were pointed out. Braverman and Snyder (1987) identified a 5-year-old male who presented with band keratopathy as the first sign of proximal renal tubular acidosis.
Autosomal recessive proximal renal tubular acidosis (AR pRTA) is a rare form of proximal renal tubular acidosis (pRTA; see this term) characterized by an isolated defect in the proximal tubule leading to the decreased reabsorption of bicarbonate and consequentially to urinary bicarbonate wastage along with additional characteristic clinical features. Epidemiology The precise prevalence is unknown but it is thought to be a rare disease. Clinical description As in other forms of pRTA, hyperchloremic acidosis is a presenting feature and onset usually occurs in childhood. Manifestations include ocular abnormalities (band keratopathy, glaucoma, and cataracts), intellectual disability and severe growth retardation. Other features like dental enamel defects, basal ganglia calcification and pancreatitis are sometimes present.
Ching et al. (2005) pointed out that cardiac transcription factor TBX5 (601620) strongly regulates expression of MYH6, but mutant forms of TBX5, which cause Holt-Oram syndrome (HOS; 142900), do not regulate MYH6.
A number sign (#) is used with this entry because of evidence that atrial septal defect (ASD4) with other congenital heart disease but no conduction defects or noncardiac abnormalities is caused by heterozygous mutation in the TBX20 gene (606061) on chromosome 7p14. For a discussion of genetic heterogeneity in atrial septal defect, see ASD1 (108800). Clinical Features Kirk et al. (2007) identified 2 families with congenital heart defects, in which affected individuals displayed a complex spectrum of cardiac developmental abnormalities, including defects in septation, chamber growth, and valvulogenesis, and heterozygous mutation in the TBX20 gene. The proband of the first family had ASD, which was corrected surgically in early childhood. Her grandmother had a small ventriculoseptal defect (VSD), and her mother had a large patent foramen ovale (PFO) with a permanent left-to-right blood shunt.
An ostium secundum atrial septal defect is a type of congenital heart defect called an atrial septal defect (ASD). An ASD is a hole in the wall (septum) between the two upper chambers of the heart (the atria). ASDs can be classified by location. An ostium secundum ASD is a hole in the center of the atrial septum. Normally, the right side of the heart pumps oxygen-poor blood to the lungs, while the left side pumps oxygen-rich blood to the body. An ASD allows blood from both sides to mix, causing the heart to work less efficiently.
He was born to a 34-year-old mother and an unrelated 37-year-old father. Features of the syndrome from which the patient suffered included extraordinary hirsutism, marked brachycephaly, abnormal position of thumbs, pes cavus with claw toes, an abnormal face, and mental retardation.
Scoliosis can occur as a feature of other conditions, including a variety of genetic syndromes. However, adolescent idiopathic scoliosis typically occurs by itself, without signs and symptoms affecting other parts of the body.
Scoliosis may occur secondary to other hereditary disorders including Marfan syndrome (154700), dysautonomia (223900), neurofibromatosis (see 162200), Friedreich ataxia (see 229300), and muscular dystrophies.
Franceschini et al. (2004) suggested that despite the clinical and radiologic variability, the unique proximal metaepiphyseal appearance of the humeri makes the syndrome easily identifiable. The changes in the humeri were widening of proximal metaphyses, striking flattening of the proximal epiphyses, and lateral bulging of proximal diaphyses.
Rhizomelic dysplasia, Patterson-Lowry type is a rare primary bone dysplasia characterized by short stature, severe rhizomelic shortening of the upper limbs associated with specific malformations of humeri (including marked widening and flattening of proximal metaphyses, medial flattening of the proximal epiphyses, and lateral bowing with medial cortical thickening of the proximal diaphyses), marked coxa vara with dysplastic femoral heads and brachimetacarpalia.
Differential diagnosis Differential diagnosis includes childhood absence epilepsy, juvenile myoclonic epilepsy, Jeavons syndrome (see these terms). Genetic counseling The transmission is still unknown although an increased risk for first degree related parents to develop JME may exist.
Winawer et al. (2003) concluded that there are distinct genetic effects on absence and myoclonic seizures, and suggested that examining seizure types as opposed to syndromes may be more useful in linkage studies.