Singleton-Merten syndrome

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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

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

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.

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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 |

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Last updated: 1/1/2021

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Diagnosis Diagnosis

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

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

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

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

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.

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References References

Singleton Merten syndrome. NORD. https://rarediseases.org/rare-diseases/singleton-merten-syndrome/.
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.
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/.
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/.