Sindromul Marinesco-Sjgren sau sindromul Marinesco-Garland, sindromul

Garland-Moorhouse, sindromul Sjgren II, sindromul Marinesco-SjgrenGarland, sindromul Torsten, sindromul Torsten Sjgren , este un sindrom
neurologic ereditar rar (au fost descrise peste 100 de persoane cu acest sindrom),
transmis autozomal recesiv, caracterizat prin ataxie cerebeloas cu atrofie
cerebeloas, disdiadocochinezia, dizartrie, cataract cu debut precoce, retard
intelectual moderat pn la sever, hipotonie i slbiciune muscular, statur mic,
diverse anomalii scheletice, inclusiv scolioz, hipogonadism hipergonadotropic.
Cu toate c muli aduli au un handicap sever, durata de via pare a fi aproape de
normal.
A fost numit dup Gheorghe Marinescu (1863 - 1938), neurolog romn,
profesor la Bucureti, i Karl Gustaf Torsten Sjgren (1896 - 1974), psihiatru i
genetician suedez, primii care au descris aceast boal. n 1931 Gheorghe
Marinescu a descris pentru prima dat 4 bolnavi care sufereau de aceast
afeciune.[1] Sjgren, n 1950, a raportat 14 cazuri similare n Suedia.[2]. n 1953 doi
neurologi britanici Hugh Garland and Doreen Moorhouse au descris 2 bolnavi cu
sindromul Marinesco-Sjgren.
Sindromul Marinesco-Sjgren este o boal autozomal recesiv provocat
de o mutaie a genei SIL1, localizat pe regiunea 5q31 a cromozomului 5;
gena SIL1 a fost identificat prin secvenializarea ADN.
Tablou clinic

Ataxie cerebeloas cu atrofie cerebeloas.

Debut precoce (nu neaprat congenital) a cataractei.

Retard psihomotor (dizabilitate intelectual uoar pn la sever).

Miopatie, slbiciune muscular i hipotonie.

Hipogonadism hipergonadotropic (de exemplu, insuficiena gonadal primar).

Statur scurt.

Diverse anomalii ale scheletului: scolioz, scurtarea oaselor metacarpiene,

metatarsiene i a falangelor; coxa valga, pes planovalgus i pectus carinatum.

Dizartrie.

Strabism i nistagmus.

Evoluie

Copiii cu sindromul Sjgren-Marinesco (SMS) sunt nscui dup sarcini

necomplicate.

Copiii cu SMS, de obicei, prezint hipotonie muscular n copilaria timpurie.

Slbiciunea muscular distal i proximal se observ n prima decad a vieii.

Mai trziu, apare ataxia troncular cerebeloase, disdiadochochinezia, dizartrie.

Funcia motorie se agraveaz progresiv n civa ani, apoi se stabilizeaz la o

vrst imprevizibil i la un anumit grad de severitate. Multe persoane afectate
nu sunt capabile s mearg fr ajutor.

Cataracta bilateral nu este neaprat congenital, dar se poate dezvolta rapid i

de obicei necesit extracia cristalinului n primul deceniu de via.
Nistagmusul i strabismul sunt prezente.

Etapele de dezvoltare psihomotorie sunt ntrziate. Dizabilitaea intelectual

variaz de la uoar pn la sever.

Multe persoane cu SMS au o statura mic i grade variabile de scolioz.

Gravitatea afectrilor scheletice se coreleaz cu severitatea de ansamblu a SMS.

Dei muli aduli au un handicap sever, durata de viata n SMS pare a fi aproape
de normal.

Diagnosticul clinic
Sindromul Marinesco-Sjgren (SMS) ar trebui s fie luate n considerare la
persoanele cu urmtoarele semne clinice:

Ataxie cerebeloas cu atrofie cerebeloas

Debut precoce (nu neaprat congenital) a cataractei

Retard psihomotor

Miopatie, slbiciune muscular i hipotonie

Caracteristici adiionale:

Hipogonadism hipergonadotropic (de exemplu, insuficiena gonadal primar)

Statur scurt

Diverse anomalii ale scheletului (scolioza, scurtarea oaselor metacarpiene,

metatarsiene i a falangelor; coxa valga, pes planovalgus i pectus carinatum.)

Dizartrie

Strabism i nistagmus

Diagnosticul paraclinic
Electromiografia prezint caracteristicile unei miopatii.

Imagistica. La persoanele cu SMS clasic, studii neuroimagistice, cum ar fi

imagistica prin rezonana magnetic (MRI) arat o atrofie cerebeloas, de
obicei, mai pronunat n vermis dect n emisfere. Un cortex cerebelar T2hiperintens a fost raportat la persoanele cu SMS care au o mutaie SIL1.

Imagistic muscular arat o distrofie sever cu nlocuirea esutului muscular

cu esut adipos i conjunctiv.

Radiografiile osoase arat o scolioza, scurtarea oaselor metacarpiene,

metatarsiene i a falangelor; coxa valga, pes planovalgus; i pectus carinatum.

Concentraia creatinkinazei serice (CK) este normal sau moderat crescut (de
obicei de 2-4 ori peste limitele superioare normale).

Biopsie muscular. Microscopie optic arat variaii n mrimea fibrelor

musculare, fibre atrofice, substituie adipoas, i formaiuni vacuolare bordate.
Microscopie electronic pune n eviden vacuole autofagice, spirale
membranoase i structuri dublu-membranare electronodense asociate cu nuclee,
care sunt considerate a fi o caracteristic ultrastructural specific a MSS.

http://www.orpha.net/consor/cgi-bin/OC_Exp.php?Lng=FR&Expert=559 .0
http://omim.org/clinicalSynopsis/248800
http://www.ncbi.nlm.nih.gov/books/NBK1192/

Marinesco-Sjogren Syndrome (or Marinescu-Sjogren

Syndrome) is a very rare genetic disorder characterized
by ataxia (balance and coordination problems), juvenile
cataracts, generally some degree of cognitive delay, and
very small stature. About 100-200 cases of MSS have
been diagnosed worldwide.
What are the symptoms of MSS?
Some symptoms occur in almost all reported cases of MSS. These symptoms
include cataracts (progressive loss of transparency of the eye lens), ataxia (impaired
ability to coordinate movement), hypotonia (floppiness), short
stature, dysarthria (slow, weak, or imprecise speech due to weakness
or incoordination of speech muscles), and mental retardation (generally in the mildmoderate range). Other symptoms such ashypergonadotropic
hypogonadism (decreased function of the ovary/testis), nystagmus (involuntary,
rhythmic movements of the eyes) and skeletal abnormalities are reported less
frequently.
How is MSS inherited?
MSS is autosomal recessive. It occurs with equal frequency in males and females. If
both parents are carriers, there is a 25% chance that any child will have the
disorder. In November 2005, a gene (SIL1) was identified that is responsible for
about half of the known cases of MSS.
How prevalent is MSS?
MSS is very rare. About 100-200 cases have been reported in the literature. It has
been reported in numerous countries including the United
States,Japan, Scandinavia, Italy, England, France, Kuwait, and others. Many reported
cases are consanguinous (parents are related).
How is a child diagnosed with MSS?
In most cases, the first signs of a problem is hypotonia (floppiness). The infant does
not develop good head control and does not achieve motor milestones (rolling, sitting,

standing, walking) at a typical age. Generally the child is referred by the pediatrician
to a pediatric neurologist, developmental pediatrician, and/or geneticist. Tests often
include extensive blood and urine tests, MRI (magnetic resonance imaging), nerve
conduction studies, and in some cases, skin and muscle biopsies. By the age of one,
small stature usually becomes more apparent. Cataracts appear in early childhood and
can develop quickly. The child generally achieves good mobility with a walker or
crutches, but independent walking is unlikely due to ataxia and muscle weakness.
Other signs of cognitive delay likely appear (delays in speech and language, self-help,
social skills, and academic skills).
What can I expect as my child grows older?
The medical literature reports a wide-range of scenarios for the MSS patient. The
variation is probably due to a combination of individual differences, increased
availability of early intervention and educational opportunities sinces the 1960s, and
uncertainty in diagnosis. Most patients continue to use walkers and crutches for
mobility. There are some reports of increasing weakness with age which may require
use of a wheelchair. Many people live to a relatively old age (some into the 70's).
Cognitive function ranges anywhere from moderate retardation to near-normal.
How tall is my child likely to get?
This chart shows how some MSS girls and boys compare to the general population.
How can I help my child with MSS?
Early intervention (including physical therapy, occupational therapy, and speech
therapy) and careful selection of educational programs are critical. Selection of a
supportive team of doctors, therapists, and educators who communicate well with the
family can significantly affect outcome. Learn as much as possible about the disorder
and communicate with others.
What else do I need to know?
When the cataracts significantly impair vision, the child will require cataract
extraction followed by insertion of intraocular lenses. Alternatively they can wear
cataract glasses or contact lenses. Glaucoma is a potential risk in children you have
had cataract surgery, particularly when the cataracts are removed in the first year of
life.
Many children with MSS wear foot/ankle orthotics (braces) to provide proper
alignment and improved stability.

What other syndromes are similar to MSS?

Differential diagnosis (see medical summary) includes:
Congenital Cataract Facial Dysmorphism Neuropathy Syndrome (CCFDN)
Mucolipidosis IV
Lowe Syndrome
Congenital Disorders of Glycosylation
Zellweger Syndrome
Some children once suspected to have MSS have later been diagnosed with:
Mitochrondrial Disease
Trichothiodystrophy
Leukodystrophy
Marinesco-Sjgren Syndrome (MSS, OMIM 248800) is a rare, autosomal recessive
disorder featuring cataracts, cerebellar ataxia, mental retardation, muscle weakness,
short stature, and frequently hypergonadotropic hypogonadism.
MSS is usually evident at birth because of hypotonia. The cataracts are often not
present at birth but may appear rapidly during childhood. Motor milestones are
significantly delayed with ataxia becoming noticeable by the time the child can sit.
Most patients are eventually able to ambulate with a walker. Linear growth is poor
and pubertal development may not occur because of hypergonadotropic
hypogonadism. Mental retardation is generally mild to moderate in severity if it is
present at all. Dysarthria is common. Neurologic deterioration is slow to absent and
prolonged survival is possible, but the muscle weakness may be progressive in
adulthood. Less commonly reported features include optic atrophy, brachydactyly,
and cone epiphyses.
MSS is inherited as an autosomal recessive trait with complete penetrance in both
sexes. The genetic defect is currently unknown, but the gene has been mapped to
chromosome 5q31. Over 100 cases have been reported. It is panethnic, but very rare
except in genetic isolates, such as one in rural Alabama.
The diagnosis should be suspected based on the clinical symptomatology. An
ophthalmologic exam (cataracts) and magnetic resonance imaging of the brain
(cerebellar atrophy particularly involving the vermis) can be helpful. Muscle biopsy
findings are generally non-specific, although ragged red fibers and abnormal
mitochondria have been reported. Multilamellar inclusions can be present in muscle

and conjunctival biopsies as well as in cultured fibroblasts. Metabolic testing is

normal.
Treatment is supportive and based on symptomatology. Removal of the cataracts and
placement of an artificial lens implant is often required to preserve vision. Physical
and occupational therapy, special education, and computers are essential given their
visual and motor problems as well as dysarthria. Hormonal replacement therapy is
needed if hypogonadism is present.
The differential diagnosis includes: MSS with chylomicronemia (607692), congenital
cataracts, facial dysmorphism, and neuropathy (604168), mitochondrial disorders, and
the carbohydrate deficient glycoprotein syndromes.