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Marinesco-Sjogren Syndrome

OMIM ID:

autosomal recessive

Marinesco-Sjogren Syndrome

Alternate Names

MSS

Defective Genes

SIL1

Clinical Characteristics

Ocular Features

Congenital cataracts are one of the cardinal features of Marinesco-Sjogren syndrome but lens opacities may have a later onset and may be progressive as well.  Strabismus and nystagmus are sometimes present.

Systemic Features

Non-ocular features include cerebellar atrophy, psychomotor developmental delays, mental retardation, and muscle weakness.  Dysarthria is common.  The myopathy has its onset in childhood and is progressive with weakness, hypotonia, and atrophy eventually leading to total disability in some cases.  Progression of motor dysfunction may, however, stabilize in some patients but at an unpredictable level.  Infants are often ‘floppy babies’.  MRI studies reveal cerebellar atrophy.  Serum creatine kinase levels are increased and muscle biopsies show chronic myopathic changes.  Skeletal features include short stature, pectus carinatum, and secondary kyphoscoliosis and foot deformities.  Bone abnormalities may be seen in the digits.

Genetics

Inheritance

This is an autosomal recessive condition resulting from mutations in the SIL1 gene (5q31).  It is sometimes confused with the condition known as congenital cataracts, facial dysmorphism, and neuropathy (604168) with which it shares some clinical features.  The two conditions are genetically distinct since they are caused by mutations in different genes.

See also Muscular Dystrophy, Congenital Cataracts, with Cataracts and Intellectual Disability for a similar disorder caused by a different mutation.

Pedigree

Autosomal recessive

In order for autosomal recessive disorders to be expressed, offspring generally must inherit two mutations, one from each carrier parent.  Carriers with only one mutation, such as the parents, do not have clinical disease.  Note that carrier parents can expect that 1 in 4 children (25%) will inherit both mutations and have the disorder, 2 in 4 children (50%) will be carriers like their parents, while 1 in 4 children (25%) inherit neither mutation.

Image
Sample pedigree of autosomal recessive inheritance

In order for autosomal recessive disorders to be expressed, offspring generally must inherit two mutations, one from each carrier parent. Carriers with only one mutation, such as the parents, do not have clinical disease. Note that carrier parents can expect that 1 in 4 children (25%) will inherit both mutations and have the disorder, 2 in 4 children (50%) will be carriers like their parents, while 1 in 4 children (25%) inherit neither mutation.

Treatment & Management

Visually significant cataracts may need to be removed in the first decade of life.  Skeletal deformities may benefit from surgery and hormone therapy should be considered in specific cases.

Selected Resources

Publications

Displaying 1 - 3 of 3

Genetic identity of Marinesco–Sjögren/myoglobinuria and CCFDN syndromes

PubMedID: 11805249

Linkage to 18qter differentiates two clinically overlapping syndromes: congenital cataracts-facial dysmorphism-neuropathy (CCFDN) syndrome and Marinesco-Sjögren syndrome

PubMedID: 12414825

The gene disrupted in Marinesco-Sjögren syndrome encodes SIL1, an HSPA5 cochaperone

PubMedID: 16282978