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Marinesco-Sjögren Syndrome

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Copyright 1992, 1995, 2004, 2010

NORD is very grateful to William R. Wilcox, MD, PhD, Medical Genetics Institute, Cedars-Sinai Medical Center; Professor of Pediatrics, UCLA School of Medicine, for assistance in the preparation of this report.

Synonyms of Marinesco-Sjögren Syndrome

Disorder Subdivisions

General Discussion

Marinesco-Sjögren syndrome (MSS) is a rare genetic disorder that affects multiple organ systems of the body. Common symptoms include difficulty coordinating voluntary movements due to degeneration (atrophy) of the cerebellum (cerebellar ataxia), clouding of the lenses of the eyes (cataracts), delays in the acquisition of skills requiring the coordination of muscular and mental activity (psychomotor development), diminished muscle tone (hypotonia), and progressive muscle weakness. Many affected individuals exhibit additional physical abnormalities. Although Marinesco-Sjögren syndrome can be associated with significant disability, lifespan is often unaffected. Marinesco-Sjögren syndrome is caused by mutations of the SIL1 gene and at least one other, presently unknown, gene.


Some symptoms of Marinesco-Sjögren syndrome are often present at birth (congenital) including diminished muscle tone (hypotonia), a condition sometimes referred to as "floppy baby". Cataracts can also be present at birth, but more often develop rapidly during early childhood. Cataracts occur when the lenses of the eyes become clouded preventing light from being focused onto the retina and thereby affecting vision. In most cases, cataracts affect both eyes (bilateral).

Individuals Marinesco-Sjögren syndrome have difficulties coordinating voluntary movements due to a small cerebellum (cerebellar ataxia). The cerebellum is the part of the brain that plays a role in maintaining balance and posture as well as coordinating voluntary movements. In most cases, ataxia is usually readily evident around the time a child can sit up.

Affected infants may also exhibit significant delays in reaching developmental milestones that require the coordination of physical (motor) and mental activity (psychomotor development) as well as speech. Muscle weakness may grow progressively worse in adulthood.

As affected individuals age, additional symptoms may become apparent including ataxia that primarily affects the torso (truncal ataxia) and impaired ability to perform rapidly alternating movements (dysdiadochokinesia). The degree of severity of motor dysfunction will vary from one person to another. Many affected individuals eventually can walk with an assistive device such as a walker. Other individuals, however, may require the use of a wheelchair.

The intellectual abilities of individuals Marinesco-Sjögren syndrome can vary greatly. In some individuals intelligence is unaffected; others develop mild to moderate cognitive impairment. Neurological deterioration usually does not occur in Marinesco-Sjögren syndrome or may be extremely slow. In addition, some individuals may have difficulty speaking or slurred speech (dysarthria). Certain symptoms of Marinesco-Sjögren syndrome (e.g., vision problems, speech difficulties) make it easy to underestimate the intelligence of an affected child.

Individuals with Marinesco-Sjögren syndrome usually exhibit growth deficiencies that can ultimately lead to short stature. Short stature refers to individuals who are significantly below average height for a person of the same age and sex. In some cases, affected individuals also have hypergonadotropic hypogonadism, a condition characterized by defective development or function of the ovaries or testes (gonads). Hypergonadotropic hypogonadism causes delays in the start of puberty and the development of secondary sexual characteristics and contributes to the development of short stature.

Less frequently, additional symptoms have been associated with Marinesco-Sjögren syndrome. These symptoms include rapid, involuntary eye movements (nystagmus), misalignment of the eyes (strabismus), and degeneration of the main nerve of the eyes that transmits nerve impulses from the retina to the brain (optic atrophy). A variety of skeletal malformations have been reported including side-to-side curvature of the spine (scoliosis), abnormally short fingers and toes (brachydactyly), and an abnormal "cone-shape" to the end portions of the long bones (cone epiphyses).

Although the severity of Marinesco-Sjögren syndrome can vary from one person to another and some affected individuals may be significantly disabled, lifespan is usually unaffected.


Marinesco-Sjögren syndrome is often caused by mutation of the SIL1 gene. It is inherited as an autosomal recessive trait. Genetic diseases are determined by the combination of genes for a particular trait that are on the chromosomes received from the father and the mother.

Recessive genetic disorders occur when an individual inherits the same abnormal gene for the same trait from each parent. If an individual receives one normal gene and one gene for the disease, the person will be a carrier for the disease, but usually will not show symptoms. The risk for two carrier parents to both pass the defective gene and, therefore, have an affected child is 25 percent with each pregnancy. The risk to have a child who is a carrier like the parents is 50 percent with each pregnancy. The chance for a child to receive normal genes from both parents and be genetically normal for that particular trait is 25 percent. The risk is the same for males and females.

Investigators have determined that the SIL1 gene is located on the long arm (q) of chromosome 5 (5q31). Chromosomes, which are present in the nucleus of human cells, carry the genetic information for each individual. Human body cells normally have 46 chromosomes. Pairs of human chromosomes are numbered from 1 through 22 and the sex chromosomes are designated X and Y. Males have one X and one Y chromosome and females have two X chromosomes. Each chromosome has a short arm designated "p" and a long arm designated "q". Chromosomes are further sub-divided into many bands that are numbered. For example, "chromosome 5q31" refers to band 31 on the long arm of chromosome 5. The numbered bands specify the location of the thousands of genes that are present on each chromosome.

The SIL1 gene contains instructions for creating (encoding) a protein that has a specific role in the body. A mutation of the SIL1 gene results in the production of a defective protein that cannot carry out its proper function, which, ultimately, results in the signs and symptoms of Marinesco-Sjögren syndrome. Researchers believe that the protein product of the SIL1 gene is involved in protein folding. Protein folding is a normal process in which a protein folds into a three-dimensional structure. This process is required for a protein to carry out its normal function. Defective protein folding is believed to cause abnormal proteins to accumulate in the endoplasmic reticulum, the extensive membrane network located in all cells including muscle cells.

Some individuals with Marinesco-Sjögren syndrome do not have a mutation of the SIL1 gene, which suggests that another gene(s) may also cause the disorder (genetic heterogeneity). The other gene(s) that may play a role in the development of Marinesco-Sjögren syndrome have not been identified.

Affected Populations

Marinesco-Sjögren syndrome affects males and females in equal numbers. More than 200 cases have been reported in the medical literature. The exact incidence of the disorder in the general population is unknown. Marinesco-Sjögren syndrome can affect all ethnic groups (panethnic), but most cases have occurred in isolated populations in rural areas.

Related Disorders

Symptoms of the following disorders can be similar to those of Marinesco-Sjögren syndrome. Comparisons may be useful for a differential diagnosis.

(C)ongenital (C)ataracts, (F)acial (D)ysmorphism, and (N)europathy (CCFDN) syndrome is an extremely rare genetic disorder with signs and symptoms that overlap with Marinesco-Sjögren syndrome including the presence of cerebellar ataxia, cataracts, muscle disease (myopathy), skeletal malformations, short stature, and developmental delays. Individuals with CCFDN may also exhibit symptoms not associated with Marinesco-Sjögren syndrome including nerve disease affecting the nerves outside the central nervous system (peripheral neuropathy), an abnormally thin and flat cornea (microcornea) and distinctive facial features (facial dysmorphism). Identification of the gene for CCFDN enabled researchers to clearly establish that Marinesco-Sjögren syndrome and CCFDN were distinct disorders despite the overlapping clinical findings. CCFDN is caused by mutations of CTDP1 gene located on the long arm of chromosome 18 (18q23). It is inherited as an autosomal recessive trait.

Congenital disorders of glycosylation refers to a group of rare inherited metabolic disorders that share similar but not identical genetic changes (mutations) and biochemical characteristics. These disorders were once called "carbohydrate-deficient glycoprotein syndrome". These disorders involve the metabolic activity of glycoproteins, complex chemical compounds created by attaching a simple or complex sugar molecule to a specific protein. Glycoproteins play key roles in the development and maintenance of the cell membrane, endocrine glandular function, and protein transport, and are active in specific parts of the brain (Golgi apparatus). Attaching the sugar to the protein is a process involving many enzymes, and a shortage or lack of any one of these enzymes causes the build-up of intermediate chemical compounds. The accumulation of these compounds is the triggering device of the disorder. Congenital disorders of glycosylation may affect many different parts of the body but are most serious when they involve the central and peripheral nervous systems. Congenital disorders of glycosylation can several different organ systems and can cause many of the symptoms seen in Marinesco-Sjögren syndrome including impaired coordination and balance (cerebellar ataxia) due to underdevelopment (hypoplasia) of certain portions of the brain (cerebellum), cognitive impairment, delays in the acquisition of skills that require the coordination of mental and muscular activity (psychomotor retardation), skeletal malformations, and/or visual impairment. Additional symptoms are often present. Congenital disorders of glycosylation are inherited as autosomal recessive genetic traits. (For more information on this disorder, choose "congenital disorders of glycosylation" as your search term in the Rare Disease Database.)

Mitochondrial disorders are a group disorders characterized by mutations affecting the parts of the cell that release energy (mitochondria). Mitochondrial diseases often hamper the ability of affected cells to break down food and oxygen and produce energy. In most mitochondrial disorders, abnormally high numbers of defective mitochondria are present in the cells of the body. Mitochondrial diseases often affect more than one organ system of the body. Most mitochondrial disorders are associated with neurological and muscular abnormalities. (For more information on these disorders, choose the specific mitochondrial disorder name as your search term in the Rare Disease Database.)

Several extremely rare disorders may also have symptoms similar to those found in individuals with Marinesco-Sjögren syndrome. These disorders include ataxia-microcephaly-cataract syndrome, cataract-ataxia-deafness-retardation syndrome, and familial Danish dysplasia.

Standard Therapies

A diagnosis of Marinesco-Sjögren syndrome may be suspected based upon the identification of characteristic findings. A diagnosis can be confirmed by a thorough clinical evaluation, a detailed patient history and a variety of specialized tests including an eye (ophthalmologic) exam to detect cataracts and magnetic resonance imaging (MRI) to detect characteristic changes in the brain (e.g., cerebellar atrophy). Imaging studies of muscle may show significant damage to muscle tissue and the abnormal accumulation of fat and connective tissue.

Molecular genetic testing (which can identify a mutation of the SIL1 gene) is available on a clinical basis. Prenatal diagnosis of Marinesco-Sjögren syndrome is possible if the SIL1 gene mutation is known to run in a family.

There is no specific treatment for individuals with Marinesco-Sjögren syndrome. Treatment 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 asses and treat skeletal problems (orthopedists), eye specialists (ophthalmologists), and other healthcare professionals may need to systematically and comprehensively plan an affect child's treatment.

Surgery may be necessary to remove cataracts and, in some cases, to implant artificial lenses. Orthotic devices such as walkers may be required. If hypergonadotropic hypogonadism is present, then hormone replacement therapy may be administered around the time puberty is expected.

Early intervention is important in ensuring that children with Marinesco-Sjögren syndrome reach their highest potential. Services that may be beneficial may include special education programs tailored to an individual's specific needs, occupational therapy, physical therapy, and other medical, social, and/or vocational services.

Genetic counseling may be of benefit for affected individuals and their families. Other treatment is symptomatic and supportive.

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

For information about clinical trials sponsored by private sources, contact:

Marinesco-Sjögren Syndrome Resources

NORD Member Organizations:

(To become a member of NORD, an organization must meet established criteria and be approved by the NORD Board of Directors. If you're interested in becoming a member, please contact Susan Olivo, Membership Manager, at solivo@rarediseases.org.)

Other Organizations:


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Lagier-Tourenne C, Chaigne D, Gong J, et al. Linkage to 18qter differentiates two clinically overlapping syndromes: congenital cataracts-facial dysmorphism-neuropathy (CCFDN) syndrome and Marinesco-Sjögren syndrome. J Med Genet. 2002;39:838-843.

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Report last updated: 2010/04/28 00:00:00 GMT+0