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aortic stenosis ; Talipes equinovarus ; Tendon rupture ; Unerupted tooth ; Waddling gait Associated Genes IFIH1 (Withdrawn symbols: Hlcd, IDDM19, MDA-5, MDA5 ) Mouse Orthologs Ifih1 (Withdrawn symbols: 9130009C22Rik [mousephenotype.org]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

• 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]

• Skin Disease

  Resources NIH/NationaI Institute of Arthritis and Musculoskeletal and Skin Diseases Information Clearinghouse One AMS Circle Bethesda, MD 20892-3675 USA Tel: (301)495-4484 Fax: (301)718-6366 Tel: (877)226-4267 TDD: (301)565-2966 Email: [email protected] [healthmedicinet.com]

  The effects of the El Niño Southern Oscillation on skin and skin-related diseases: a me... [allmedx.com]

  Resources NIH/National Institute of Arthritis and Musculoskeletal and Skin Diseases Information Clearinghouse One AMS Circle Bethesda, MD 20892-3675 USA Tel: (301)495-4484 Fax: (301)718-6366 Tel: (877)226-4267 TDD: (301)565-2966 Email: [email protected] [metrohealth.net]

  Given the progressive disease course, in particular due to refractory skin inflammation, this led us to consider treatment with the JAK inhibitor ruxolinitib. [ped-rheum.biomedcentral.com]

• Skin Rash

  Mild form of Singleton-Merten syndrome may be associated wth only one symptom, such as a skin rash ( psoriasis ). [xpertdox.com]

  Individuals with a mild form of Singleton-Merten syndrome may show only one symptom, such as a skin rash (psoriasis). [rarediseases.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]

• Arthritis

  British Society for Paediatric and Adolescent Rheumatology Psoriatic arthritis or could it be Singleton-Merten syndrome? Abstract Aims To describe Singleton-Merten Syndrome as an unusual cause of arthritis associated with a psoriasiform rash. [adc.bmj.com]

  Arthritis resulting from calcified tendons as well as ligaments of the interphalangeal and metacarpophalangeal joints may occur in young adults. The skin is often scaly and dry with psoriatic lesions. [disorders.eyes.arizona.edu]

  Arthritis Rheumatol. 2017 Oct;69(10):2081-2091. doi: 10.1002/art.40179. Epub 2017 Aug 22. Arthritis Rheumatol. 2017. PMID: 28605144 Free PMC article. [pubmed.ncbi.nlm.nih.gov]

• 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]

• Joint Dislocation

  Short forearm Bruising susceptibility Joint dislocation Bilateral cryptorchidism Lipodystrophy Expanded metacarpals with widened medullary cavities Hyperextensible skin Radioulnar synostosis Sparse eyelashes Cutis laxa Accelerated skeletal maturation [mendelian.co]

  Chondrodysplasia with congenital joint dislocations, CST3 type 47. Desbuquois Dysplasia 48. gPAPP Dysplasia 49. Pseudodiastrophic Dysplasia 50. [axon.es]

  Dislocations; OMIM:602611 Spondyloepiphyseal Dysplasia with Coronal Craniosynostosis, Cataracts, Cleft Palate, and Mental Retardation OMIM:183850 Spondyloepiphyseal Dysplasia with Punctate Corneal Dystrophy OMIM:184200 Spondylolisthesis OMIM:609616 Spondylomegaepiphyseal [informatics.jax.org]

  Contractures, and Facial Dysmorphism Mental Retardation, Short Stature, Facial Anomalies, and Joint Dislocations Mental Retardation, Skeletal Dysplasia, and Abducens Palsy Mental Retardation, X-Linked + Merlob Grunebaum Reisner Syndrome MERRF Syndrome [rgd.mcw.edu]

• Seizure

  […] progressive encephalopathy with onset in the first months of life characterised by cerebrospinal fluid (CSF) lymphocytosis and calcifications in the basal ganglia.1 It manifests with irritability, psychomotor retardation, spasticity, dystonia, epileptic seizures [analesdepediatria.org]

  Genital Hypoplasia Microcephaly Seizures Mental Retardation Heart Disorders Microcephaly Sparse Hair Mental Retardation Seizures Microcephaly with Chemotactic Defect and Transient Hypogammaglobulinemia Microcephaly with Chorioretinopathy, Autosomal Dominant [rgd.mcw.edu]

  Early neurologic impairment is evident including developmental delay, intellectual disability, ataxia, dysarthria, sensorineural hearing loss, myoclonus and seizures. [mendelian.co]

  5; BFIS5 OMIM:121200 Seizures, Benign Familial Neonatal, 1; BFNS1 OMIM:121201 Seizures, Benign Familial Neonatal, 2; BFNS2 OMIM:608217 Seizures, Benign Familial Neonatal, 3; BFNS3 OMIM:269720 Seizures, Benign Familial Neonatal, Autosomal Recessive OMIM [informatics.jax.org]

• Spastic Paraplegia

  Patient 1 in this report presented with spastic paraplegia, a phenotype that has not been described earlier in SMS specifically; however, IFIH1 sequence variations have been linked previously to non‐syndromic spastic paraplegia (Crow et al., ; Rutsch [deepdyve.com]

  Spastic Paraplegia 33, Autosomal Dominant; SPG33 OMIM:300750 Spastic Paraplegia 34, X-Linked; SPG34 OMIM:612319 Spastic Paraplegia 35, Autosomal Recessive; SPG35 OMIM:613096 Spastic Paraplegia 36, Autosomal Dominant; SPG36 OMIM:611945 Spastic Paraplegia [informatics.jax.org]

  25 Spastic paraplegia 26 Spastic paraplegia 29 Spastic paraplegia 3 Spastic paraplegia 31 Spastic paraplegia 39 Spastic paraplegia 4 Spastic paraplegia 5A Spastic paraplegia 5B Spastic paraplegia 6 Spastic paraplegia 7 Spastic paraplegia 8 Spastic paraplegia [personalizedcause.com]

  […] ataxia + Spastic Diplegia Infantile Type Spastic Paraplegia and Evans Syndrome Spastic Paraplegia Epilepsy Mental Retardation Spastic Paraplegia with Kallmann Syndrome Spastic Paraplegia, Ataxia, and Mental Retardation SPASTIC PARAPLEGIA, INTELLECTUAL [rgd.mcw.edu]

  Most common symptoms of AICARDI-GOUTIÈRES SYNDROME Seizures Microcephaly Ptosis Spasticity Hypertonia More info about AICARDI-GOUTIÈRES SYNDROME SOURCES: ORPHANET UMLS Potential gene panels for IFIH1 gene Hereditary Spastic Paraplegia Panel Panel By Greenwood [mendelian.co]

• Confusion

  The scientists demonstrated precisely how mistakes in a molecular proofreading system can lead to confusion and generate out-of-control interferon signaling, setting off development of autoimmune disease. [nbbgist.com]

  Discussion The oral phenotype of Singleton–Merten syndrome was confusing in the literature. The most frequent anomaly concerns root, dental eruption, and premature tooth loss. [frontiersin.org]

  Signs and symptoms such as confusion, seizures and loss of consciousness require emergency treatment. From the Department of Radiology, Cincinnati Children’s, have yourself a The child then voids while monitoring with intermittent fluoroscopy. [mykidadvisor.com]

• Paresis

  […] target esterase gene mutation Spastic paraplegia epilepsy mental retardation Spastic paraplegia facial cutaneous lesions Spastic paraplegia nephritis deafness Spastic paraplegia neuropathy poikiloderma Spastic paraplegia with precocious puberty Spastic paresis [personalizedcause.com]

  Spastic Paraplegia with Associated Extrapyramidal Signs OMIM:270805 Spastic Paraplegia with Myoclonic Epilepsy OMIM:182815 Spastic Paraplegia with Neuropathy and Poikiloderma OMIM:182820 Spastic Paraplegia with Precocious Puberty OMIM:270850 Spastic Paresis [informatics.jax.org]

  Retardation SPASTIC PARAPLEGIA, INTELLECTUAL DISABILITY, NYSTAGMUS, AND OBESITY Spastic Paraplegia, Optic Atrophy, Microcephaly, and XY Sex Reversal Spastic Paraplegia, Sensorineural Deafness, Mental Retardation, and Progressive Nephropathy Spastic Paresis [rgd.mcw.edu]

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]

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]

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]

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]