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Singleton Merten syndrome

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Copyright 1997, 1998, 2004, 2008, 2012

NORD is very grateful to Emile Mohler, MD, Director of Vascular Medicine, University of Pennsylvania Health System, for assistance in the preparation of this report.

Synonyms of Singleton Merten syndrome

Disorder Subdivisions

General Discussion

Singleton-Merten syndrome is an extremely rare, multisystem disorder the major characteristics of which are tooth abnormalities (dental dysplasia), calcifications in the aorta, the major artery of the body, and certain valves of the heart (i.e., aortic and mitral valves), as well as progressive thinning and loss of protein of the bones (osteoporosis), especially the upper and back portions of the skull (cranium). Other physical findings usually associated with Singleton-Merten syndrome may include generalized muscle weakness; progressive loss or wasting away of muscle tissue (atrophy); growth retardation, possibly resulting in short stature; delays in motor development; a skin condition characterized by thickened patches of red, scaly skin, particularly on the fingers; and/or malformation of the hips and/or feet. It appears that, in some cases, Singleton-Merten syndrome is present as a result of a random (sporadic) mutation that occurs for no apparent reason. In other cases, an autosomal dominant pattern of inheritance has been suggested.

Symptoms

Singleton-Merten Syndrome, an extremely rare disorder, is characterized by abnormalities of the teeth (dental dysplasia), abnormal accumulation of calcium deposits (calcifications) in the major artery of the body (aorta) and certain valves of the heart (i.e., aortic and mitral valves), and/or progressive thinning and loss of protein of the bones (osteoporosis). Between the ages of four to 24 months, most affected infants experience generalized muscle weakness and loss or wasting away (atrophy) of muscle tissue. In approximately half of the reported cases, such symptoms begin after an episode of illness associated with an elevation in body temperature (febrile illness). Affected infants may also exhibit delays in general physical (somatic) development, possibly resulting in short stature, and/or delays in the ability to coordinate muscles and perform certain tasks (motor development).

Abnormalities affecting the teeth also occur at an early age in individuals with Singleton-Merten Syndrome. Affected infants may develop cavities (caries) and lose their primary (deciduous) teeth prematurely. Certain secondary (permanent) teeth may not develop (erupt) or may erupt late; those permanent teeth that do develop are usually malformed (dysplastic). In some cases, permanent teeth may also be lost prematurely.

By late infancy or early childhood, affected individuals may experience symptoms associated with the progressive accumulation of calcium deposits (calcifications) in the major artery of the body (aorta) and on certain valves of the heart (i.e., aortic and mitral). The aorta arises from the lower pumping chamber of the heart (left ventricle) and supplies oxygen-rich (oxygenated) blood to all the arteries of the body (excluding the pulmonary artery). In individuals with Singleton-Merten Syndrome, deposits of calcium (calcifications) form in the portion of the aorta nearest the heart (proximal thoracic aorta). The accumulation of calcium deposits is progressive and typically causes blockage and narrowing of the aorta (calcific aortic stenosis), obstructing the flow of oxygenated blood. In some cases, abnormal calcium deposits may also develop around the valve on the left side of the heart (mitral valve calcification). As a result of calcification of these various structures, affected individuals may experience high blood pressure (hypertension), abnormal transmission of electrical impulses (conduction) that coordinate the activity of the heart muscle (heart block), abnormal contractions of the heart (systolic murmurs), and/or abnormal enlargement of the heart (cardiomegaly). By late adolescence, the heart may be unable to pump blood effectively (heart failure), leading to life-threatening complications.

Infants with Singleton-Merten Syndrome may also experience abnormal thinning and weakness of the bones (osteoporosis). As a result, bones are frequently brittle and may fracture easily. Osteoporosis may occur in the skull and the long bones of the arms and legs, but is most prominent in the bones of the hands and fingers.

Other findings associated with Singleton-Merten Syndrome may include malformations of the hips and feet that may occur due to muscle weakness; wearing away (erosion) of the bones in the tips of the fingers (terminal phalanges); and/or a chronic skin condition characterized by red, thick, scaly patches of skin (psoriasiform skin eruption). In some cases, affected individuals may have abnormal accumulation of pressure of the fluid of the eye (glaucoma) and/or abnormal sensitivity to light (photosensitivity).

Causes

Singleton-Merten Syndrome is an extremely rare disorder that appears to occur randomly for no apparent reason (sporadically). Some reported cases seem to suggest possible autosomal dominant inheritance.

Affected Populations

Singleton-Merten Syndrome is an extremely rare inherited disorder that, in theory, affects males and females in equal numbers. However, in reported cases, females have been affected more frequently than males (3:1). Five individual cases and one family (kindred) with multiple affected members have been reported in the medical literature.

Related Disorders

Symptoms of the following disorders can be similar to those of Singleton-Merten Syndrome. Comparisons may be useful for a differential diagnosis:

The Ectodermal Dysplasias (ED) are a group of diseases typically characterized by abnormalities of the head and face (craniofacial) area, the hair, teeth, nails, and/or skin. In some cases, the abnormalities associated with some of the Ectodermal Dysplasias may be similar to findings associated with Singleton-Merten Syndrome. Some of the Ectodermal Dysplasias may also be characterized by abnormalities of the heart and vascular system similar to those associated with Singleton-Merten Syndrome. (For more information on these disorders, choose "Ectodermal Dysplasia" or the exact disease name in question as your search term in the Rare Disease Database).

Standard Therapies

Diagnosis
The diagnosis of Singleton-Merten syndrome may be suspected during infancy based upon the identification of characteristic physical findings (i.e., muscle weakness, muscle atrophy, dental abnormalities, and skeletal changes). A diagnosis may be confirmed by a thorough clinical evaluation, a detailed patient history, and/or a variety of specialized tests. The identification of calcium deposits in the aorta, in association with the other findings described above, strongly suggests a diagnosis of Singleton-Merten syndrome.

X-ray tests may be used to confirm the presence and extent of calcium deposits (calcifications) in the aorta. Obstruction or narrowing (stenosis) of the heart valves, particularly the aortic and mitral valves, may be confirmed by cardiac catheterization. During this procedure, a small hollow tube (catheter) is inserted into a large vein and threaded through the blood vessels leading to the heart. This procedure allows physicians to determine the rate of blood flow through the heart and measure the pressure within the heart. X-ray studies may also be performed to confirm the presence and extent of osteoporosis. Osteoporosis may be suspected when bone fractures occur more frequently than usual. X-ray tests may also reveal abnormal widening of the hollow parts of the bones that contain soft fatty tissue (bone marrow cavities) within the bones of the hands and/or feet (e.g., metacarpals, carpals, phalanges, etc.).

Treatment
The treatment of Singleton-Merten syndrome is directed toward the specific symptoms that are apparent in each individual. Treatment may require the coordinated efforts of a team of specialists. Pediatricians, surgeons, specialists who diagnose and treat abnormalities of the heart (cardiologists), dental specialists, physical therapists, specialists who diagnose and treat conditions of the skin (dermatologists), and other health care professionals may need to systematically and comprehensively plan an affected child's treatment.

Specific therapies for the treatment of Singleton-Merten syndrome are symptomatic and supportive. Special services that may be beneficial to affected children may include special social support, physical therapy, and other medical, social, and/or vocational services. Genetic counseling will be of benefit for affected individuals and their families.

Investigational Therapies

Information on current clinical trials is posted on the Internet at www.clinicaltrials.gov. All studies receiving U.S. government funding, and some supported by private industry, are posted on this government web site.

For information about clinical trials being conducted at the NIH Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:

Tollfree: (800) 411-1222 (800) 411-1222
TTY: (866) 411-1010
Email: prpl@cc.nih.gov

For information about clinical trials sponsored by private sources, contact:
www.centerwatch.com

Organizations related to Singleton Merten syndrome

References

TEXTBOOK
Gorlin RJ, Cohen MMJr, Levin LS, eds. Syndromes of the Head and Neck. 3rd ed. Oxford University Press, London, UK; 1990:910.

JOURNAL ARTICLES
Feigenbaum A, Kumar A, Weksberg R. Singleton-Merten (S-M) syndrome: autosomal dominant transmission with variable expression. Am J Hum Genet. 1988;43:A48.

Gay BB Jr, Kuhn JP. A syndrome of widened medullary cavities of bone, aortic calcification abnormal dentition, and muscular weakness (the singleton-merten syndrome). Radiology. 1976;118:389-95.

INTERNET
Online Mendelian Inheritance in Man (OMIM). The Johns Hopkins University. _ Singleton-Merten Syndrome. Entry No: 182250. Last Edited March 17, 2004. Available at: http://www.ncbi.nlm.nih.gov/omim/. Accessed February 15. 2012.

Report last updated: 2012/03/12 00:00:00 GMT+0