Skip to main content
U.S. Department of Health & Human Services
National Institutes of Health
NCATS

COVID-19 is an emerging, rapidly evolving situation.

Get the latest public health information from CDC: https://www.coronavirus.gov (link is external)
Get the latest research information from NIH: https://www.nih.gov/coronavirus (link is external)

National Center for Advancing and Translational Sciences National Center for Advancing and Translational Sciences Genetic and Rare Diseases Information Center, a program of the National Center for Advancing and Translational Sciences Genetic and Rare Diseases Information Center, a program of the National Center for Advancing and Translational Sciences
1-888-205-2311
Menu Search
1-888-205-2311
Menu
  • Home
  • Diseases expand submenu for Diseases
    • Browse A-Z
    • Find Diseases By Category expand submenu for Find Diseases By Category
      • Autoimmune / Autoinflammatory diseases
      • Bacterial infections
      • Behavioral and mental disorders
      • Blood Diseases
      • Chromosome Disorders
      • Congenital and Genetic Diseases
      • Connective tissue diseases
      • Digestive Diseases
      • Ear, Nose, and Throat Diseases
      • Endocrine Diseases
      • Environmental Diseases
      • Eye diseases
      • Female Reproductive Diseases
      • Fungal infections
      • Heart Diseases
      • Hereditary Cancer Syndromes
      • Immune System Diseases
      • Kidney and Urinary Diseases
      • Lung Diseases
      • Male Reproductive Diseases
      • Metabolic disorders
      • Mouth Diseases
      • Musculoskeletal Diseases
      • Myelodysplastic Syndromes
      • Nervous System Diseases
      • Newborn Screening
      • Nutritional diseases
      • Parasitic diseases
      • Rare Cancers
      • RDCRN
      • Skin Diseases
      • Viral infections
    • List of FDA Orphan Drugs
    • GARD Information Navigator
    • FAQs About Rare Diseases
  • Guides expand submenu for Guides
    • Patients, Families and Friends expand submenu for Patients, Families and Friends
      • How to Find a Disease Specialist
      • Tips for the Undiagnosed
      • Support for Patients and Families
      • Tips for Finding Financial Aid
      • Help with Travel Costs
      • How to Get Involved in Research
      • FAQs About Chromosome Disorders
      • Medical and Science Glossaries
    • Healthcare Professionals expand submenu for Healthcare Professionals
      • Caring for Your Patient with a Rare Disease
      • ICD Coding for Rare Diseases
      • FindZebra Diagnosis Assist Tool
    • Researchers expand submenu for Researchers
      • Finding Funding Opportunities
    • Teachers and Students expand submenu for Teachers and Students
      • Teaching Resources
  • News expand submenu for News
    • In The Spotlight
    • News Archive
    • Connect with GARD
    • Media Requests
  • About GARD expand submenu for About GARD
    • Contact GARD
    • About GARD
    • Videos
    • Brochures and Publications
  • En Español expand submenu for En Español
    • Enfermedades
    • Contacte GARD
    • Guías de Información expand submenu for Guías de Información
      • Preguntas Más Frecuentes Sobre Enfermedades Raras
      • Como Encontrar un Especialista en su Enfermedad
      • Consejos Para una Condición no Diagnosticada
      • Consejos Para Pacientes y Familias
      • Consejos Para Obtener Ayuda Financiera Para Una Enfermedad
      • Participe en Estudios de Investigación
      • Preguntas Más Frecuentes Sobre los Trastornos Cromosómicos
    • Sobre GARD
  • Home
© Positive Exposure
banner showing people with disabilities and/or their relatives
  1. Home
  2. Diseases
  3. Singleton-Merten syndrome
print
  • Table of Contents expand submenu for Table of Contents
    • Summary
    • Symptoms
    • Diagnosis
    • Treatment
    • Find a Specialist
    • Research
    • Learn More
    • GARD Answers
    • References
  • Browse A-Z
  • Find Diseases By Category expand submenu for Find Diseases By Category
    • Autoimmune / Autoinflammatory diseases
    • Bacterial infections
    • Behavioral and mental disorders
    • Blood Diseases
    • Chromosome Disorders
    • Congenital and Genetic Diseases
    • Connective tissue diseases
    • Digestive Diseases
    • Ear, Nose, and Throat Diseases
    • Endocrine Diseases
    • Environmental Diseases
    • Eye diseases
    • Female Reproductive Diseases
    • Fungal infections
    • Heart Diseases
    • Hereditary Cancer Syndromes
    • Immune System Diseases
    • Kidney and Urinary Diseases
    • Lung Diseases
    • Male Reproductive Diseases
    • Metabolic disorders
    • Mouth Diseases
    • Musculoskeletal Diseases
    • Myelodysplastic Syndromes
    • Nervous System Diseases
    • Newborn Screening
    • Nutritional diseases
    • Parasitic diseases
    • Rare Cancers
    • RDCRN
    • Skin Diseases
    • Viral infections
  • List of FDA Orphan Drugs
  • GARD Information Navigator
  • FAQs About Rare Diseases
You can help advance
rare disease research!
You can help advance rare disease research!
toolbox
Find out how with the NCATS Toolkit.

Singleton-Merten syndrome


Información en español Title


How can we make GARD better? We want to hear from you.
Provide Feedback

Other Names:
Merten-Singleton syndrome; SM syndrome; Widened medullary cavities of bone, aortic calcification, abnormal dentition, and muscular weakness; Merten-Singleton syndrome; SM syndrome; Widened medullary cavities of bone, aortic calcification, abnormal dentition, and muscular weakness; Syndrome of widened medullary cavities of the metacarpals and phalanges, aortic calcification and abnormal dentition; Singleton-Merten dysplasia See More
Categories:
Congenital and Genetic Diseases; Immune System Diseases; Musculoskeletal Diseases

Summary Summary


Listen
Singleton-Merten syndrome is a very rare disease that affect many organs. The main features are tooth abnormalities with gum infection; calcifications in the aorta artery and in certain valves of the heart (i.e., aortic and mitral valves); and progressive thinning and weakening of the bones (osteoporosis), especially in the upper and back portions of the skull. 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 psoriasis; malformation of the hips and/or feet and limbs or fingers, joint problems, tendon rupture, distinct facial features, and vision problems due to glaucoma.[1][2][3] Severe systemic lupus erythematosus can also occur with Singleton-Merten syndrome.[2]  Singleton-Merten syndrome is caused by mutations in the IFIH1 gene, and in the DDX58  genes (which causes anatypical form of Singleton-Merten syndrome where there are no teeth problems).[1][2] Inheritance is autosomal dominant, but it may also occur sporadically (in individuals with no history of the condition in their family).[1] 

Commonly, people with type I interferonopathies are treated with high doses of intravenous methylprednisolone, oral prednisone and intravenous immunoglobulins during the acute phases with often only partial control of the flares. There are studies trying to find a more effective treatment.[2][4]

The genes  causing Singeleton-Merten syndrome can activate type I interferon (IFN1) responses. Diseases related to INF1 are known as type I interferonopathies.[4] Type I interferonopathies are a group of rheumatic diseases that are frequently severe and have an early-onset.  These  diseases include  Aicardi-Goutières syndrome,  familial chilblain lupus,  spondyloenchondrodysplasia, the proteasome associated autoinflammatory syndromes, IFN-stimulated gene 15 (ISG15) deficiency, Singleton-Merten syndrome, STING-associated vasculopathy with onset in infancy (SAVI).[4]
Last updated: 11/20/2017

Symptoms Symptoms


Listen
Singleton-Merten syndrome main symptoms are:[1][2]
  • Cavities and early loss of baby (primary) teeth, deformed permanent teeth with late eruption or early lost of these teeth
  • Blockage and narrowing of the aorta due to calcified aortic stenosis leading to obstructing the flow of oxygenated blood
  • Mitral valve calcification causing high blood pressure (hypertension)
  • Abnormal transmission of the electrical impulses of the heart muscle (heart block)
  • Abnormal contractions of the heart (systolic murmurs)
  • Abnormal enlargement of the heart (cardiomegaly), with inability of the heart to pump blood causing heart failure by late  adolescence
  • Abnormal and progressive thinning and weakness of the bones (osteoporosis) resulting in  bones that are frequently brittle and may fracture easily, affecting the skull and the long bones of the arms and legs, and the bones of the hands and fingers
Other symptoms that may occur may include: [1][2][3]
  • Generalized muscle weakness and loss of muscle tissue (muscle atrophy) starting between the ages of four to 24 months, that usually begin after a feverish illness
  • Growth delay resulting in short stature Delay in acquiring motor skills
  • Malformation of the hips and/or feet and limbs or fingers Destruction of the tips of the bones of the fingers
  • Chronic skin condition characterized by red, thick, scaly patches of skin (psoriasiform skin eruption)
  • Vision loss due to an abnormal accumulation of pressure of the fluid of the eye (glaucoma) and/or abnormal sensitivity to light (photosensitivity)
  • Neurologic problems,
  • Poor muscle tone (hypotonia)
  • Joint problems and tendon rupture
  • Distinct facial features such a wide forehead with a high hairline, drooped eyelids (ptosis), decreased space between the nose and upper lip, and a thin upper lip border (vermillion).
  • Severe systemic lupus erythematosus 
Last updated: 11/20/2017

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

Showing of 41 |
Medical Terms Other Names
Learn More:
HPO ID
Percent of people who have these symptoms is not available through HPO
Aortic arch calcification 0005303
Aortic valve calcification 0004380
Aortic valve stenosis
Narrowing of aortic valve
0001650
Autosomal dominant inheritance 0000006
Broad forehead
Increased width of the forehead
Wide forehead
[ more ]
0000337
Cardiomegaly
Enlarged heart
Increased heart size
[ more ]
0001640
Carious teeth
Dental cavities
Tooth cavities
Tooth decay
[ more ]
0000670
Congestive heart failure
Cardiac failure
Cardiac failures
Heart failure
[ more ]
0001635
Coxa valga 0002673
Cutaneous photosensitivity
Photosensitive skin
Photosensitive skin rashes
Photosensitivity
Sensitivity to sunlight
Skin photosensitivity
Sun sensitivity
[ more ]
0000992
Decreased body weight
Decreased weight
Low body weight
Low weight
Weight less than 3rd percentile
[ more ]
0004325
Expanded metacarpals with widened medullary cavities 0006232
Expanded metatarsals with widened medullary cavities 0008102
Expanded phalanges with widened medullary cavities 0006112
Generalized hypotonia
Decreased muscle tone
Low muscle tone
[ more ]
0001290
Genu valgum
Knock knees
0002857
Glaucoma 0000501
High anterior hairline
High frontal hairline
0009890
Hip dislocation
Dislocated hips
Dislocation of hip
[ more ]
0002827
Hip subluxation
Partial hip dislocation
0030043
Hypoplasia of the maxilla
Decreased size of maxilla
Decreased size of upper jaw
Maxillary deficiency
Maxillary retrusion
Small maxilla
Small upper jaw
Small upper jaw bones
Upper jaw deficiency
Upper jaw retrusion
[ more ]
0000327
Hypoplasia of the tooth germ
Decreased size of tooth bud
Small tooth bud
[ more ]
0006353
Hypoplastic distal radial epiphyses 0006386
Mitral valve calcification 0004382
Muscle fiber atrophy
Muscle fiber degeneration
0100295
Muscle weakness
Muscular weakness
0001324
Muscular hypotonia
Low or weak muscle tone
0001252
Myopia
Close sighted
Near sighted
Near sightedness
Nearsightedness
[ more ]
0000545
Onycholysis
Detachment of nail
0001806
Osteolytic defects of the phalanges of the hand
Breakdown of small bones of fingers
0009771
Osteoporosis 0000939
Pes cavus
High-arched foot
0001761
Recurrent respiratory infections
Frequent respiratory infections
Multiple respiratory infections
respiratory infections, recurrent
Susceptibility to respiratory infections
[ more ]
0002205
Shallow acetabular fossae 0003182
Short stature
Decreased body height
Small stature
[ more ]
0004322
Smooth philtrum 0000319
Subvalvular aortic stenosis
Narrowing of blood vessel below aortic heart valve
0001682
Talipes equinovarus
Club feet
Club foot
Clubfeet
Clubfoot
[ more ]
0001762
Tendon rupture
Rupture of tendons
Ruptured tendon
[ more ]
0100550
Unerupted tooth
Failure of eruption of tooth
0000706
Waddling gait
'Waddling' gait
Waddling walk
[ more ]
0002515
Showing of 41 |
Do you have more information about symptoms of this disease? We want to hear from you.
Last updated: 1/1/2021
Do you have updated information on this disease? We want to hear from you.

Diagnosis Diagnosis


Listen
The diagnosis of Singleton-Merten syndrome is based on the signs and symptoms including the teeth abnormalities, calcification of the aorta and heart valves and bone changes, as well as muscle weakness and atrophy. Other special exams that may help to make the diagnosis include:[1]
  • X-ray tests to confirm the presence and extent of calcifications in the aorta, osteoporosis, and bone defects
  • Cardiac catheterization showing obstruction or narrowing (stenosis) of the heart valves, particularly the aortic and mitral valves. Catherization is a procedure where a hollow tube (catheter) is inserted into a large vein and threaded through the blood vessels leading to the heart, allowing to determine the rate of blood flow through the heart and to measure the pressure within the heart.
Last updated: 11/20/2017

Treatment Treatment


Listen
There is still no cure. The treatment is done to treat the symptoms that may be present. The Singleton-Merten syndrome is an interferonopathy. Drug options that have improved symptoms during the acute phase in people with an interferonopathy include: [1][2][4]
  • Intravenous methylprednisone
  • Oral prednisone
  • Intravenous immunoglobulin
Other medications that have being used include anti-rheumatic drugs such as metrotrexate, mycophenolate mofetil, azathioprine, as well as infliximab, etanercept, anakinra, tocilizumab, and rituximab but have not been effective in most cases.

Other possible treatment include:[2][4]
  • Treatment of tooth decay and use of dental implants as well as regular visits to the dentist
  • Treatment of heart problems which may include surgery and medications
  • Glaucoma treatment with eye drops, pills, laser surgery, and/or traditional surgery
  • Ostoeporosis treatment such as medications known as  biphosphonates
  • Skin problems treatment 
Treatment may require a team of medical specialists, depending on the different symptoms. Special social support, physical therapy, and other medical, social, and/or vocational services may benefit the people with the disease. Genetic counseling would be of benefit for affected individuals and their families.
Last updated: 11/20/2017

Find a Specialist Find a Specialist


Listen

If you need medical advice, you can look for doctors or other healthcare professionals who have experience with this disease. You may find these specialists through advocacy organizations, clinical trials, or articles published in medical journals. You may also want to contact a university or tertiary medical center in your area, because these centers tend to see more complex cases and have the latest technology and treatments.

If you can’t find a specialist in your local area, try contacting national or international specialists. They may be able to refer you to someone they know through conferences or research efforts. Some specialists may be willing to consult with you or your local doctors over the phone or by email if you can't travel to them for care.

You can find more tips in our guide, How to Find a Disease Specialist. We also encourage you to explore the rest of this page to find resources that can help you find specialists.

Healthcare Resources

  • To find a medical professional who specializes in genetics, you can ask your doctor for a referral or you can search for one yourself. Online directories are provided by the American College of Medical Genetics and the National Society of Genetic Counselors. If you need additional help, contact a GARD Information Specialist. You can also learn more about genetic consultations from Genetics Home Reference.

Research Research


Listen

Research helps us better understand diseases and can lead to advances in diagnosis and treatment. This section provides resources to help you learn about medical research and ways to get involved.

Clinical Research Resources

  • The Centers for Mendelian Genomics program is working to discover the causes of rare genetic disorders. For more information about applying to the research study, please visit their website.

Learn More Learn More


Listen

These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

Where to Start

  • The National Organization for Rare Disorders (NORD) has a report for patients and families about this condition. NORD is a patient advocacy organization for individuals with rare diseases and the organizations that serve them.

In-Depth Information

  • The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
  • Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine. 
  • Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
  • PubMed is a searchable database of medical literature and lists journal articles that discuss Singleton-Merten syndrome. Click on the link to view a sample search on this topic.

GARD Answers GARD Answers


Listen

Questions sent to GARD may be posted here if the information could be helpful to others. We remove all identifying information when posting a question to protect your privacy. If you do not want your question posted, please let us know. Submit a new question

  • Do you have any information on this syndrome? My daughter has the condition. See answer


Have a question? Contact a GARD Information Specialist.

References References


  1. Singleton Merten syndrome. NORD. https://rarediseases.org/rare-diseases/singleton-merten-syndrome/.
  2. Pettersson M, Bergendal B, Norderyd J, Nilsson D, Anderlid BM, Nordgren A & Lindstrand A. Further evidence for specific IFIH1 mutation as a cause of Singleton-Merten syndrome with phenotypic heterogeneity. Am J Med Genet A. May, 2017; 173(5):1396-1399. https://www.ncbi.nlm.nih.gov/pubmed/28319323.
  3. Ghadiam H & Mungee S. Singleton Merten Syndrome: A Rare Cause of Early Onset Aortic Stenosis. Case Reports in Cardiology. 2017; 2017:https://www.hindawi.com/journals/cric/2017/8197954/.
  4. Volpi S, Picco P, Caorsi R, Candotti F & Gattorno M. Type I interferonopathies in pediatric rheumatology. Pediatric Rheumatology Online Journal. 2016; 14:35. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4893274/.
Do you know of a review article? We want to hear from you.
You can help advance
rare disease research!
You can help advance rare disease research!
toolbox
Find out how with the NCATS Toolkit.

Share this content:

Share this content:

twitter-icon facebook-icon contact-icon link-icons

Copy Link

Link copied to your clipboard.

printer-icon

You May Be Interested In

How to Find a Disease Specialist

How to Find a Disease Specialist

Tips for the Undiagnosed

Tips for the Undiagnosed

Support for Patients and Families

Support for Patients and Families

Tips for Finding Financial Aid

Tips for Finding Financial Aid

Help with Travel Costs

Help with Travel Costs

How to Get Involved in Research

How to Get Involved in Research

FAQs About Chromosome Disorders

FAQs About Chromosome Disorders

Medical and Science Glossaries

Medical and Science Glossaries

Caring for Your Patient with a Rare Disease

Caring for Your Patient with a Rare Disease

ICD Coding for Rare Diseases

ICD Coding for Rare Diseases

FindZebra Diagnosis Assist Tool

FindZebra Diagnosis Assist Tool

Finding Funding Opportunities

Finding Funding Opportunities

Teaching Resources

Teaching Resources

placeholder for the horizontal scroll slider Back to top
GARD Home NCATS Home Site Map Browse Glossary A-Z Privacy Notice Disclaimer Accessibility FOIA OIG

If you have problems viewing PDF files, download the latest version of Adobe Reader

For language access assistance, contact the NCATS Public Information Officer

Genetic and Rare Diseases Information Center (GARD) - PO Box 8126, Gaithersburg, MD 20898-8126 - Toll-free: 1-888-205-2311

contact gard Office of Rare Disease Research Facebook Page Office of Rare Disease Research on Twitter
Listen