Patients often present with muscular weakness, failure to thrive, abnormal dentition, glaucoma, psoriatic skin lesions, aortic calcification and musculoskeletal abnormalities. [ncbi.nlm.nih.gov]

We present a young man with dyspnea who was noted to have aortic stenosis in the background of glaucoma, psoriasis, dental anomalies, hand and foot deformities, Achilles tendinitis, osteopenia, and nephrolithiasis. [unboundmedicine.com]

The patient in our sample that presented with such a variant had a neonatal presentation and currently has the most severe form of illness of the 3. [analesdepediatria.org]

Signs and symptoms[edit] The patients often present with a history of fever of unknown origin, muscular weakness, poor development, abnormal dentition, normal serum calcium, phosphorus, and alkaline phosphatase levels. [en.wikipedia.org]

• Short Stature

  Dental concerns also emerged with delayed eruption and very malformed teeth with short roots. She was of proportional short stature with height at the 3rd centile at 10 years. [adc.bmj.com]

  Other findings may include neurologic problems, generalized short stature, muscle weakness; poor muscle tone ( hypotonia ); progressive wasting of the muscles ( muscle atrophy ); heart arrhythmia, growth and developmental delay ; skin problems such as [rarediseases.info.nih.gov]

  This anomaly may sometimes, not always, be associated with short stature or short stature syndromes. Short roots, whether generalized or localized, may or may not pose any clinical problem. [indjos.com]

  stature ; Smooth philtrum ; Subvalvular aortic stenosis ; Talipes equinovarus ; Tendon rupture ; Unerupted tooth ; Waddling gait Associated Genes IFIH1 (Withdrawn symbols: Hlcd, IDDM19, MDA-5, MDA5 ) Mouse Orthologs Ifih1 (Withdrawn symbols: 9130009C22Rik [mousephenotype.org]

• Poor Growth

  Russell-Silver syndrome | Genetic and Rare Diseases Information ... ; Russell-Silver syndrome (RSS) is a rare condition associated with poor growth both .... Do you have more information about symptoms of this disease? ..... [xdlrwffz.gq]

  Learn more Other less relevant matches: Medium match MOSAIC VARIEGATED ANEUPLOIDY SYNDROME 2; MVA2 Mosaic variegated aneuploidy syndrome is an autosomal recessive disorder characterized by poor growth and variable phenotypic manifestations, such as facial [mendelian.co]

• Weight Loss

  Broad thumb Conotruncal defect Nephrocalcinosis Medullary nephrocalcinosis Infantile hypercalcemia Polyuria Hypercalciuria Hypercalcemia Calcinosis Dehydration Hyperkeratosis Nephrolithiasis Thick lower lip vermilion Lethargy Abnormality of the eye Weight [mendelian.co]

  Determinants of neonatal weight loss in term-infants ; specific association with pre-pregnancy maternal body mass index and infant feeding mode. Arch Dis Child Fetal Neonatal Ed 2011 ; 96 : 217-22 45. RENEVIER B, LE RAY C, CABROL D, GOFFINET F. [xn--epop-inserm-ebb.fr]

• Streptococcal Pharyngitis

  Rapid-antigen detection tests for group a streptococcal pharyngitis: revisiting false-positive results using polymerase chain reaction testing. J Pediatr. 2013 Jun;162(6):1282-4, 4 e1. 27. Collinot H, Azria E. [xn--epop-inserm-ebb.fr]

• Failure to Thrive

  Patients often present with muscular weakness, failure to thrive, abnormal dentition, glaucoma, psoriatic skin lesions, aortic calcification and musculoskeletal abnormalities. [ncbi.nlm.nih.gov]

  Top matches: Medium match HYPERCALCEMIA, INFANTILE, 1; HCINF1 Infantile hypercalcemia is characterized by severe hypercalcemia, failure to thrive, vomiting, dehydration, and nephrocalcinosis. [mendelian.co]

  All the patients had failure to thrive (Table S1 in the Supplementary Appendix ). By 7 years of age, Patient 5 had symmetric seropositive polyarthritis with carpal-bone erosions and progressive ulnar deviation (Fig. [nejm.org]

• Cardiomegaly

  [citation needed] Typical radiographic appearances include skeletal demineralization, expanded shafts of the metacarpals and phalanges with widenend medullary cavities, cardiomegaly, and intramural calcification of the proximal aorta with occasional extension [en.wikipedia.org]

  Classification bone, developmental, genetic, immunological, rheumatological of childhood, systemic and rheumatological Phenotypes Aortic arch calcification ; Aortic valve calcification ; Aortic valve stenosis ; Autosomal dominant inheritance ; Broad forehead ; Cardiomegaly [mousephenotype.org]

• Dental Caries

  Pachyonychia congenita (caries; early loss) 49. Papillon-Lefèvre S. (early loss) 50. Prader-Willi S. (dental caries; enamel hypoplasia) 51. Rieger S. (hypodontia; microdontia) 52. Robinow S. (delayed eruption) 53. Romberg S. (delayed eruption) 54. [gamuts.isradiology.org]

  MMP13 polymorphism decreases risk for dental caries. [journal.frontiersin.org]

  While AGS is characterized by inflammatory neurodegeneration and skin disease, the clinical features of SGMRT comprise abnormal calcification of the aorta and cardiac valves, alveolar bone loss, dental caries, osteoporosis, psoriasis, and muscular weakness [ped-rheum.biomedcentral.com]

• Erythema

  Related symptoms: Autosomal recessive inheritance Skeletal muscle atrophy Pectus excavatum Erythema Arthritis SOURCES: OMIM SCTID More info about KERATOSIS PILARIS ATROPHICANS; KPA Low match IMMUNODEFICIENCY 11B WITH ATOPIC DERMATITIS; IMD11B IMD11B is [mendelian.co]

  Myalgia Eosinophilic Fasciitis Ependymona Epidermal Nevus Syndrome Epidermolysis Bullosa Epidermolytic Hyperkeratosis Epilepsy Epilepsy, Myoclonic Progressive Familial Epitheliopathy, Acute Posterior Multifocal Placoid Pigment Erdheim Chester Disease Erythema [medschool.umaryland.edu]

  We observed a moderate to severe gingival inflammation: bright surface inflammation, erythema, edema and/or hypertrophy of gingiva, and some spontaneous bleedings. We did not observe deep pockets or recessions. [frontiersin.org]

• Cutaneous Manifestation

  Jan 30th, 2019 - Aleukemic leukemia cutis (ALC) is an extremely rare cutaneous manifestation of an aggressive systemic hematological malignancy, associated with dermal infiltration by leukemic cells preceding peripheral blood involvement. [allmedx.com]

• Muscle Weakness

  Core manifestations included marked aortic calcification, dental anomalies, osteopenia and acroosteolysis, and, to a lesser extent, glaucoma, psoriasis, muscle weakness, and joint laxity. [findzebra.com]

  weakness, and joint laxity. [ncbi.nlm.nih.gov]

  Definition A form of Singleton-Merten syndrome, an autosomal dominant disorder characterized by marked aortic calcification, dental anomalies, osteopenia, acro-osteolysis, and to a lesser extent glaucoma, psoriasis, muscle weakness, and joint laxity. [uniprot.org]

  Other findings may include neurologic problems, generalized short stature, muscle weakness; poor muscle tone ( hypotonia ); progressive wasting of the muscles ( muscle atrophy ); heart arrhythmia, growth and developmental delay ; skin problems such as [rarediseases.info.nih.gov]

  Additional features included generalized muscle weakness and atrophy, and chronic psoriasiform skin eruptions. It has been reported in four unrelated patients (male and female) and in a family with multiple affected members (male). [orpha.net]

• Coxa Valga

  [citation needed] Other commonly seen radiographic findings include shallow acetabular fossa, subluxation of the femoral head, coxa valga, hypoplastic radial epiphysis, soft tissue calcifications between the radius and ulna, constriction of the proximal [en.wikipedia.org]

  valga ; Cutaneous photosensitivity ; Decreased body weight ; Expanded metacarpals with widened medullary cavities ; Expanded metatarsals with widened medullary cavities ; Expanded phalanges with widened medullary cavities ; Generalized hypotonia ; Genu [mousephenotype.org]

• Muscular Atrophy

  Type OMIM:271220 Spinal Muscular Atrophy, Scapuloperoneal OMIM:183020 Spinal Muscular Atrophy, Segmental OMIM:253400 Spinal Muscular Atrophy, Type III; SMA3 OMIM:253550 Spinal Muscular Atrophy, Type II; SMA2 OMIM:253300 Spinal Muscular Atrophy, Type [informatics.jax.org]

  atrophy type 1 with congenital bone fractures Spinal muscular atrophy type 2 Spinal muscular atrophy type 3 Spinal muscular atrophy type 4 Spinal muscular atrophy with respiratory distress 1 Spinal shock Spine rigid cardiomyopathy Spinocerebellar ataxia [personalizedcause.com]

  atrophy, microcytic anemia, and panniculitis-induced lipodystrophy syndrome, Nakajo-Nishimura syndrome PSTPIP1 Pyogenic sterile arthritis, pyoderma gangrenosum, and acne PTPRC Severe combined immunodeficiency,, T-cell negative, B-cell positive, NK cell [genda.com.ar]

  Absent speech Lower limb spasticity Muscular hypotonia of the trunk Developmental regression Skin rash Irritability Spastic paraplegia Abnormality of the cerebral white matter Lymphadenopathy Abnormality of eye movement Paraplegia Tetraplegia Brain atrophy [mendelian.co]

  Other physical findings associated with this syndrome may include generalized muscle weakness; progressive muscular atrophy; delayed motor development and eczema. [docksci.com]

• Pierre Robin Syndrome

  Phosphoglycerate Kinase Deficiency Pick's Disease Pierre Robin Syndrome Pinta Pityriasis Rubra Pilaris Pneumonia, Eosinophilic Pneumonia, Interstitial POEMS Syndrome Poland Syndrome Polyarteritis Nodosa Polychondritis Polycystic Kidney Diseases Polycystic [medschool.umaryland.edu]

• Hyperactivity

  This indicates that SMS-MDA5 is hyperactive to non-self dsRNA. According to additional in vitro studies, interferon signature genes including SIGLEC1 were upregulated in blood and dental cells derived from SMS individuals. [link.springer.com]

  Conformational changes of mutated MDA5 caused a hyperactivity of the protein in a dsRNA independent manner (Funabiki et al 2014). Thus, this mouse model supports the idea that hyperactivity of MDA5 is caused by gain-of-function mutations in MDA5. [muhaz.org]

  […] nasal bridge Falls Leukemia Skeletal muscle atrophy Alopecia Narrow mouth Severe short stature Arachnodactyly Elbow dislocation Abnormality of skin pigmentation Syndactyly Toe syndactyly Aggressive behavior Muscular hypotonia of the trunk Polydactyly Hyperactivity [mendelian.co]

  The pathogenesis is not known, but hyperactivity of the sympathetic nervous system and local hyperemia seem to play a major part in it, which is the reason for the designation. [rrnursingschool.biz]

• Stroke

  steroid-sensitive, steroidogenesis, sterol, stevenson, stiff, stiff-man, stimmler, stippling, stocco, stoelinga, stoll, stomatitis, stomatocytosis, storage, stormorken, strabismus, straddling, streptococcus, striata, striatal, striations, striato, stroke [rapsodyonline.eurordis.org]

  Thromboembolic events (strokes, myocardial infarctions) are a significant risk at any age, especially so after age 20 years, and this is responsible for considerable morbidity and mortality. [disorders.eyes.arizona.edu]

  Ischemic OMIM:606799 Stroke, Susceptibility to, 1 OMIM:243605 Stromme Syndrome; STROMS OMIM:617478 Structural Heart Defects and Renal Anomalies Syndrome; SHDRA OMIM:185300 Sturge-Weber Syndrome; SWS OMIM:184450 Stuttering, Familial Persistent, 1; STUT1 [informatics.jax.org]

  Regional osteoporosis is a typical feature of reflex sympathetic dystrophy (OMIM 604335), a condition occurring in association with a number of pathologic conditions, notably trauma, myocardial infarction, stroke, degenerative cervical spine disease and [rrnursingschool.biz]

  Cerebral arterial stenoses and stroke: novel features of Aicardi-Goutières syndrome caused by the Arg164X mutation in SAMHD1 are associated with altered cytokine expression. Hum Mutat 31:E1836-1850. [muhaz.org]

• Spastic Gait

  Over the following several years, he developed a spastic gait and contractures of the knee joints and elbows (figure 1B). [muhaz.org]

The treatment with dental implants in the extremely rare Singleton-Merten syndrome patients is a reasonable treatment option to rehabilitate maxillofacial aesthetics and establish normal function of the jaws. [ncbi.nlm.nih.gov]

Treatment Treatment Options: Glaucoma should be treated with pressure-lowering drugs and surgery. It may be possible to decalcify cardiovascular structures in select patients and to perform valve replacement. [disorders.eyes.arizona.edu]

Conclusion: The rehabilitation treatment with maxillary overdenture and mandibular partial removable denture provided better facial muscle support, restoring masticatory function and facial esthetics. [periodicos.univille.br]

Cleft palate is also addressed, with details on etiology, phenotypes, treatment timing and approaches, and dental management. [books.google.com]

Dental dysplasia was not observed in either family, nor was tendon rupture, and the disease phenotype was considered to be milder and associated with a better prognosis than classic SMS. [lasid.org]

Diagnosis and Prognosis: The diagnosis (such as glaucoma) can sometimes be made in childhood but other aspects such as arthritis and calcium deposits in the aorta and heart valves become evident somewhat later. [disorders.eyes.arizona.edu]

Pathogenic variants in IFIH1 have previously been associated with the classic Singleton-Merten syndrome, while variants in DDX58 has been described in association with a milder phenotype, which is suggested to have a better prognosis. [semanticscholar.org]

These patients exhibit features of a unique clinical syndrome of unknown etiology: generalized muscular weakness with secondary hip and foot deformities, progressive calcification of the thoracic aorta beginning in childhood, calcific aortic stenosis [ncbi.nlm.nih.gov]

To determine the molecular etiology of this disease, we performed whole-exome sequencing and targeted Sanger sequencing. [infona.pl]

Cleft palate is also addressed, with details on etiology, phenotypes, treatment timing and approaches, and dental management. [books.google.com]

Epidemiology The prevalence of all Singleton-Merten syndromes is less than 1:1,000,000. Systematic References: 1. Jang MA et al. (2015) Mutations in DDX58, which encodes RIG-I, cause atypical Singleton-Merten syndrome. 2. [moldiag.com]

Singleton-Merten dysplasia Synonyms Singleton-Merten syndrome Name in a foreign language - Inheritance Autosomal dominant CONTENT INFORMATION Textual description Etiology Forecast Differential diagnosis Treatment Diagnostic methods Antenatal diagnosis Epidemiology [retkebolesti.com]

No epidemiological studies have been reported for this very rare condition. Thought to be autosomal dominant. Linear calcification of the ascending aorta and severe calcific mixed aortic valve disease (stenotic and regurgitant). [accessanesthesiology.mhmedical.com]

Association Between Psoriasis and Sexual and Erectile Dysfunction in Epidemiologic Stud... Preview https://www.ncbi.nlm.nih.gov/pubmed/30304327 JAMA Dermatology; Molina-Leyva A, Salvador-Rodriguez L et. al. [allmedx.com]

Relevant External Links for IFIH1 Genetic Association Database (GAD) IFIH1 Human Genome Epidemiology (HuGE) Navigator IFIH1 Atlas of Genetics and Cytogenetics in Oncology and Haematology: IFIH1 No data available for Genatlas for IFIH1 Gene A genome-wide [genecards.org]

The pathophysiology of abnormal calcification is unknown but is likely linked to gain-of-function IFIH1 mutation [2]. We had a young male patient who presented for dyspnea and palpitations and was noted to have mild aortic stenosis. 2. [hindawi.com]

Pathophysiology Mutation in IFIH1 (interferon induced with helicase C domain 1) gene on 2q24.2, which encodes MDA5 (melanoma differentiation-associated protein 5) resulting in an enhanced interferon response in affected families. [accessanesthesiology.mhmedical.com]

Pathophysiology Singleton Merten syndrome appears to occur sporadically (in individuals with no history of the condition in their family) but in some cases, autosomal dominant inheritance has been suggested. [wikidoc.org]

The exact pathophysiology is unclear due to the rarity of the disease. Less than 10 clinical cases have been reported so far in the literature. [docksci.com]

Horror autoinflammaticus: the molecular pathophysiology of autoinflammatory disease. Annu Rev Immunol 2009 ;27: 621 - 668 2. Sanchez GA, de Jesus AA, Goldbach-Mansky R. [nejm.org]

In healthy wild type cells, ATP hydrolysis prevents MDA5 and RIG-I to recognize self-dsRNA thus preventing triggering of signaling. [journal.frontiersin.org]

[…] gain-of-function mutation in IFIH1: overlap between Aicardi-Goutières and Singleton-Merten syndromes. 62 Bursztejn AC...Crow YJ 26284909 2015 40 [Type I interferonopathies]. 62 Munoz J...Bessis D 26363997 2015 41 ATP hydrolysis by the viral RNA sensor RIG-I prevents [malacards.org]

Identifying the gene that causes Singleton-Merten Syndrome will also allow families with a history of the disease to potentially participate in genetic screening that could prevent them from passing the disease on to children. [al.com]

Other Possible Causes of these Symptoms * Delayed motor development * Enlarged heart * Growth retardation * Malformed teeth * Missing teeth * Muscle weakness * Osteoporosis * Progressive muscle wasting * Short stature Prevention - Singleton Merten syndrome [checkorphan.org]