Sengers Syndrome

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OMIM 57 212350 Disease Ontology 12 DOID:0080132 MedGen 42 C1859317

MeSH 44 D002386 D009202 D028361 SNOMED-CT via HPO 69 258211005 128602000 22066006 23986001 609587005 79410001 57190000 563001 398151007 398152000 26544005 276617005 444896005 59576002 233873004 45227007 302215000 415116008 409623005 129565002 248268002 237950009 267044007 16851005 248274002 84229001 more UMLS 73 C1859317

NIH Rare Diseases : ⁵³ The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs.Orpha Number: 1369Disease definitionCongenitalcataract - hypertrophic cardiomyopathy - mitochrondrial myopathy (CCM) is a mitochondrial disease (see this term) characterized by cataracts, hypertrophic cardiomyopathy, muscle weakness and lactic acidosis after exercise.EpidemiologyPrevalence of CCM is unknown; approximately 40 cases have been reported to date in disparate locations throughout the world.Clinical descriptionClinical features include congenital cataract (total or rapidly progressive), hypertrophic cardiomyopathy, muscle weakness and lactic acidosis after exercise. CCM may present in two forms, a neonatal lethal form or a chronic form. Hypertrophic cardiomyopathy is diagnosed at birth in half of the patients in both forms. Approximately half of the patients die within the first year of life due to cardiac failure. Nystagmus, strabismus, hypotonia, hyporeflexia and delayed motor development are occasional features. Marked lactic acidemia occurs with even limited muscular exertion. Patients who survive neonatal period and infancy, manifest the chronic form with stable cardiomyopathy and myopathy and have a normal intellect. Physical mobility is impaired due to muscular weakness in most patients.EtiologyIn the majority of CCM patients mutations (nonsense, frame-shift, start codon or splice site) in the AGK gene have been identified. The AGK gene encodes the mitochondrial acylglycerol kinase which plays a role in the assembly of adeninenucleotide translocator (ANT), an essential component of the oxidative phosphorylation in mitochondria. Two patients with distinct autosomal recessiveSLC25A4 mutations have been reported (one of whom had cardiomyopathy but not cataract). The SLC25A4 gene encodes the heart and muscle specific isoform 1 of the mitochondrial ANT. The etiology remains genetically unsolved in the rest of cases of CCM. The milder affected individuals carried either splice site or start codon mutations.Diagnostic methodsDiagnostic procedures include serum and urine analysis for lactic acid, radiology and echocardiogram for findings of cardiomyopathy. Muscle biopsy from cardiac and skeletal muscle reveals storage of lipid and glycogen, mitochondrial abnormalities, ANT deficiency and mild decrease of respiratory chain complexes I and IV. Genetic testing may reveal autosomal recessive mutations in AGK and SLC25A4 and it should be considered early in diagnostic workup.Differential diagnosisDifferential diagnoses include mitochondrial encephalo-cardio-myopathy due to TMEM70 deficiency, isolated ATP synthase deficiency and Barth syndrome (see these terms).Antenatal diagnosisPrenatal genetic testing may be possible for families with affected children.Genetic counselingThe reported mutations are transmitted in an autosomal recessive manner.Management and treatmentCCM patients require cataract surgery during infancy and medical management of cardiomyopathy with standard therapy. Patients may require palliative care and a wheelchair for locomotion.PrognosisApproximately half of the reported patients die in the first year of life due to cardiac failure. The longest surviving patients are in their fifth decade of life.Visit the Orphanet disease page for more resources.

MalaCards based summary : Sengers Syndrome, also known as cataract and cardiomyopathy, is related to congenital cataract-hypertrophic cardiomyopathy-mitochondrial myopathy syndrome and cataract, and has symptoms including fatigue and muscle weakness. An important gene associated with Sengers Syndrome is AGK (Acylglycerol Kinase). Affiliated tissues include skeletal muscle, heart and testes, and related phenotypes are nystagmus and muscular hypotonia

OMIM : ⁵⁷ Sengers syndrome is an autosomal recessive mitochondrial disorder characterized by congenital cataracts, hypertrophic cardiomyopathy, skeletal myopathy, exercise intolerance, and lactic acidosis. Mental development is normal, but affected individuals may die early from cardiomyopathy (summary by Mayr et al., 2012). Skeletal muscle biopsies of 2 affected individuals showed severe mtDNA depletion (Calvo et al., 2012). (212350)

UniProtKB/Swiss-Prot : ⁷⁵ Mitochondrial DNA depletion syndrome 10: An autosomal recessive mitochondrial disorder characterized by congenital cataracts, hypertrophic cardiomyopathy, skeletal myopathy, exercise intolerance, and lactic acidosis. Mental development is normal, but affected individuals may die early from cardiomyopathy.

Wikipedia : ⁷⁶ Sengers syndrome is a rare autosomal recessive condition characterised by congenital cataract,... more...

Clinical features from OMIM:

212350

Search Clinical Trials , NIH Clinical Center for Sengers Syndrome

Search GEO for disease gene expression data for Sengers Syndrome.