Singleton-Merten Syndrome

What are the other Names for this Condition? (Also known as/Synonyms)

• Merten-Singleton Syndrome
• SM Syndrome
• Widened Medullary Cavities of Bone, Aortic Calcification, Abnormal Dentition, and Muscular Weakness

What is Singleton-Merten Syndrome? (Definition/Background Information)

• Singleton-Merten Syndrome (SM Syndrome) is an extremely rare, multisystem disorder
• The major characteristics are tooth abnormalities (dental dysplasia); calcifications in the aorta and certain valves of the heart (i.e., aortic and mitral valves); and progressive thinning and loss of protein of the bones (osteoporosis), especially the upper and back portions of the skull
• Other physical findings may include generalized muscle weakness; progressive muscle atrophy; growth delay; delays in motor development; skin conditions; and/or malformation of the hips and/or feet
• It 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
• Treatment is typically directed toward the specific symptoms that are present in each individual

(Source: Singleton-Merten Syndrome; Genetic and Rare Diseases Information Center (GARD) of National Center for Advancing Translational Sciences (NCATS), USA.)

Who gets Singleton-Merten Syndrome? (Age and Sex Distribution)

• Singleton-Merten Syndrome is a rare congenital disorder. The presentation of symptoms occur after birth
• Both males and females may be affected
• Worldwide, individuals of all racial and ethnic groups may be affected

What are the Risk Factors for Singleton-Merten Syndrome? (Predisposing Factors)

• A positive family history may be an important risk factor, since Singleton-Merten Syndrome can be inherited

It is important to note that having a risk factor does not mean that one will get the condition. A risk factor increases one’s chances of getting a condition compared to an individual without the risk factors. Some risk factors are more important than others.

Also, not having a risk factor does not mean that an individual will not get the condition. It is always important to discuss the effect of risk factors with your healthcare provider.

What are the Causes of Singleton-Merten Syndrome? (Etiology)

• 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

(Source: Singleton-Merten Syndrome; Genetic and Rare Diseases Information Center (GARD) of National Center for Advancing Translational Sciences (NCATS), USA.)

Autosomal dominant: Autosomal dominant conditions are traits or disorders that are present when only one copy of the mutation is inherited on a non-sex chromosome. In these types of conditions, the individual has one normal copy and one mutant copy of the gene. The abnormal gene dominates, masking the effects of the correctly function gene. If an individual has an autosomal dominant condition, the chance of passing the abnormal gene on to their offspring is 50%. Children, who do not inherit the abnormal gene, will not develop the condition or pass it on to their offspring.

What are the Signs and Symptoms of Singleton-Merten Syndrome?

• Singleton-Merten Syndrome is characterized by abnormalities of the teeth (dental dysplasia); abnormal accumulation of calcium deposits (calcifications) in the 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, these symptoms begin after an episode of illness associated with a fever
• Affected infants may also show delays in general physical development, possibly resulting in short stature 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 and lose their primary teeth prematurely
• Certain permanent teeth may not develop or may erupt late; those permanent teeth that do develop are usually malformed. 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 aorta and on certain valves of the heart.

• The aorta arises from the lower pumping chamber of the heart (left ventricle) and supplies oxygen-rich blood to all the arteries of the body (excluding the pulmonary artery)
• In individuals with Singleton-Merten Syndrome, 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 (called 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, causing heart failure and 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)

In general, the signs and symptoms of Singleton-Merten Syndrome may include:

• Aortic arch calcification
• Aortic valve calcification
• Aortic valve stenosis
• Broad forehead
• Cardiomegaly
• Carious teeth
• Congestive heart failure
• Coxa valga
• Cutaneous photosensitivity
• Decreased body weight
• Expanded metacarpals with widened medullary cavities
• Expanded metatarsals with widened medullary cavities
• Expanded phalanges with widened medullary cavities
• Genu valgum
• Glaucoma
• High anterior hairline
• Hip dislocation
• Hip subluxation
• Hypoplasia of the maxilla
• Hypoplasia of the tooth germ
• Hypoplastic distal radial epiphyses
• Mitral valve calcification
• Muscular hypotonia
• Myopia
• Onycholysis
• Osteolytic defects of the phalanges of the hand
• Osteoporosis
• Pes cavus
• Recurrent respiratory infections
• Shallow acetabular fossae
• Smooth philtrum
• Subaortic stenosis
• Talipes equinovarus
• Tendon rupture
• Unerupted tooth
• Waddling gait

(Source: Singleton-Merten Syndrome; Genetic and Rare Diseases Information Center (GARD) of National Center for Advancing Translational Sciences (NCATS), USA.)

How is Singleton-Merten Syndrome Diagnosed?

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 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

(Source: Singleton-Merten Syndrome; Genetic and Rare Diseases Information Center (GARD) of National Center for Advancing Translational Sciences (NCATS), USA.)

Many clinical conditions may have similar signs and symptoms. Your healthcare provider may perform additional tests to rule out other clinical conditions to arrive at a definitive diagnosis.

What are the Possible Complications of Singleton-Merten Syndrome?

The complications of Singleton-Merten Syndrome may include:

• Severe heart abnormalities
• Multiple fractures during one’s lifetime
• Immobility

Complications may occur with or without treatment, and in some cases, due to treatment also.

How is Singleton-Merten Syndrome Treated?

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 would be of benefit for affected individuals and their families

(Source: Singleton-Merten Syndrome; Genetic and Rare Diseases Information Center (GARD) of National Center for Advancing Translational Sciences (NCATS), USA.)

How can Singleton-Merten Syndrome be Prevented?

Currently, Singleton-Merten Syndrome may not be preventable, since it is a genetic disorder.

• Genetic testing of the expecting parents (and related family members) and prenatal diagnosis (molecular testing of the fetus during pregnancy) may help in understanding the risks better during pregnancy
• If there is a family history of the condition, then genetic counseling will help assess risks, before planning for a child
• Active research is currently being performed to explore the possibilities for treatment and prevention of inherited and acquired genetic disorders

Regular medical screening at periodic intervals with tests and physical examinations are recommended.

What is the Prognosis of Singleton-Merten Syndrome? (Outcomes/Resolutions)

• The prognosis of Singleton-Merten Syndrome is dependent upon the severity of the signs and symptoms and associated complications, if any
• Individuals with mild conditions have better prognosis than those with severe symptoms and complications
• Typically, the prognosis may be assessed on a case-by-case basis

Additional and Relevant Useful Information for Singleton-Merten Syndrome:

Singleton-Merten Syndrome is also known by the following name: Syndrome of Widened Medullary Cavities of the Metacarpals and Phalanges, Aortic Calcification and Abnormal Dentition.

The following DoveMed website link is a useful resource for additional information:

http://www.dovemed.com/diseases-conditions/rare-disorders/