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Transcript of Sindromul Marinesco
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Sindromul Marinesco-Sjögren sau sindromul Marinesco-Garland, sindromul
Garland-Moorhouse, sindromul Sjögren II, sindromul Marinesco-Sjögren-
Garland, sindromul Torsten, sindromul Torsten Sjögren , este un sindrom
neurologic ereditar rar (au fost descrise peste 100 de persoane cu acest sindrom),transmis autozomal recesiv, caracterizat prin ataxie cerebeloasă cu atrofie
cerebeloasă, disdiadocochinezia, dizartrie, cataractă cu debut precoce, retard
intelectual moderat până la sever, hipotonie și slăbiciune musculară, statură mică,
diverse anomalii scheletice, inclusiv scolioză, hipogonadism hipergonadotropic.
Cu toate că mulți adulți au un handicap sever, durata de viață pare a fi aproape de
normală.
A fost numit după Gheorghe Marinescu (1863 - 1938), neurolog român,
profesor la București, și Karl Gustaf Torsten Sjögren (1896 - 1974), psihiatru și
genetician suedez, primii care au descris această boală. În 1931 Gheorghe
Marinescu a descris pentru prima dată 4 bolnavi care sufereau de această
afecțiune.[1] Sjögren, în 1950, a raportat 14 cazuri similare în Suedia.[2]. În 1953 doi
neurologi britanici Hugh Garland and Doreen Moorhouse au descris 2 bolnavi cu
sindromul Marinesco-Sjögren.
Sindromul Marinesco-Sjögren este o boală autozomală recesivă provocată
de o mutație a genei SIL1, localizată pe regiunea 5q31 a cromozomului 5; gena SIL1 a fost identificată prin secvențializarea ADN.
Tablou clinic
Ataxie cerebeloasă cu atrofie cerebeloasă.
Debut precoce (nu neapărat congenital) a cataractei.
Retard psihomotor (dizabilitate intelectuală ușoară până la severă).
Miopatie, slăbiciune musculară și hipotonie. Hipogonadism hipergonadotropic (de exemplu, insuficiența gonadală primară).
Statură scurtă.
Diverse anomalii ale scheletului: scolioză, scurtarea oaselor metacar piene,
metatarsiene și a falangelor; coxa valga, pes planovalgus și pectus carinatum.
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Dizartrie.
Strabism și nistagmus.
Evoluție
Copiii cu sindromul Sjögren-Marinesco (SMS) sunt născuți după sarcini
necomplicate.
Copiii cu SMS, de obicei, prezintă hipotonie musculară în copilaria timpurie.
Slăbiciunea musculară distală și proximală se observă în prima decadă a vieții.
Mai târziu, apare ataxia tronculară cerebeloase, disdiadochochinezia, dizartrie.
Funcția motorie se agravează progresiv în câțiva ani, apoi se stabilizează la o
vârstă imprevizibilă și la un anumit grad de severitate. Multe persoane afectate
nu sunt capabile să meargă fără ajutor. Cataracta bilaterală nu este neapărat congenitală, dar se poate dezvolta rapid și
de obicei necesită extracția cristalinului în primul deceniu de viață.
Nistagmusul și strabismul sunt prezente.
Etapele de dezvoltare psihomotorie sunt întârziate. Dizabilitațea intelectuală
variază de la ușoară până la severă.
Multe persoane cu SMS au o statura mică și grade variabile de scolioză.
Gravitatea afectărilor scheletice se corelează cu severitatea de ansamblu a SMS.
Deși mulți adulți au un handicap sever, durata de viata în SMS pare a fi aproape
de normală.
Diagnosticul clinic
Sindromul Marinesco-Sjögren (SMS) ar trebui să fie luate în considerare la
persoanele cu următoarele semne clinice:
Ataxie cerebeloasă cu atrofie cerebeloasă
Debut precoce (nu neapărat congenital) a cataractei Retard psihomotor
Miopatie, slăbiciune musculară și hipotonie
Caracteristici adiționale:
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Hipogonadism hipergonadotropic (de exemplu, insuficiența gonadală primară)
Statură scurtă
Diverse anomalii ale scheletului (scolioza, scurtarea oaselor metacarpiene,
metatarsiene și a falangelor; coxa valga, pes planovalgus și pectus carinatum.) Dizartrie
Strabism și nistagmus
Diagnosticul paraclinic
Electromiografia prezintă caracteristicile unei miopatii.
Imagistica. La persoanele cu SMS clasic, studii neuroimagistice, cum ar fi
imagistica prin rezonanța magnetică (MRI) arată o atrofie cerebeloasă, de
obicei, mai pronunțată în vermis decât în emisfere. Un cortex cerebelar T2-hiperintens a fost raportat la persoanele cu SMS care au o mutație SIL1.
Imagistică musculară arată o distrofie severă cu înlocuirea țesutului muscular
cu țesut adipos și conjunctiv.
Radiografiile osoase arată o scolioza, scurtarea oaselor metacarpiene,
metatarsiene și a falangelor; coxa valga, pes planovalgus; și pectus carinatum.
Concentrația creatinkinazei serice (CK) este normală sau moderat crescută (de
obicei de 2-4 ori peste limitele superioare normale). Biopsie musculară. Microscopie optică arată variații în mărimea fibrelor
musculare, fibre atrofice, substituție adipoasă, și formațiuni vacuolare bordate.
Microscopie electronică pune în evidență vacuole autofagice, spirale
membranoase și structuri dublu-membranare electronodense asociate cu nuclee,
care sunt considerate a fi o caracteristică ultrastructurală specifică 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/
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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 (impairedability to coordinate movement), hypotonia (floppiness), shortstature, dysarthria (slow, weak, or imprecise speech due to weaknessor incoordination of speech muscles), and mental retardation (generally in the mild-moderate range). Other symptoms such ashypergonadotropichypogonadism (decreased function of the ovary/testis), nystagmus (involuntary,rhythmic movements of the eyes) and skeletal abnormalities are reported lessfrequently.
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 thedisorder. In November 2005, a gene (SIL1) was identified that is responsible forabout 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 reportedcases 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 doesnot develop good head control and does not achieve motor milestones (rolling, sitting,
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standing, walking) at a typical age. Generally the child is referred by the pediatricianto a pediatric neurologist, developmental pediatrician, and/or geneticist. Tests ofteninclude extensive blood and urine tests, MRI (magnetic resonance imaging), nerveconduction 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 andcan develop quickly. The child generally achieves good mobility with a walker orcrutches, 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. Thevariation is probably due to a combination of individual differences, increasedavailability of early intervention and educational opportunities sinces the 1960s, and
uncertainty in diagnosis. Most patients continue to use walkers and crutches formobility. There are some reports of increasing weakness with age which may requireuse 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 speechtherapy) and careful selection of educational programs are critical. Selection of asupportive team of doctors, therapists, and educators who communicate well with thefamily can significantly affect outcome. Learn as much as possible about the disorderand 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 wearcataract glasses or contact lenses. Glaucoma is a potential risk in children you havehad cataract surgery, particularly when the cataracts are removed in the first year oflife.
Many children with MSS wear foot/ankle orthotics (braces) to provide properalignment and improved stability.
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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-Sjögren Syndrome (MSS, OMIM 248800) is a rare, autosomal recessivedisorder 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 aresignificantly 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 hypergonadotropichypogonadism. 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 inadulthood. Less commonly reported features include optic atrophy, brachydactyly,and cone epiphyses.
MSS is inherited as an autosomal recessive trait with complete penetrance in bothsexes. The genetic defect is currently unknown, but the gene has been mapped tochromosome 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. Anophthalmologic exam (cataracts) and magnetic resonance imaging of the brain(cerebellar atrophy particularly involving the vermis) can be helpful. Muscle biopsyfindings are generally non-specific, although ragged red fibers and abnormalmitochondria have been reported. Multilamellar inclusions can be present in muscle
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and conjunctival biopsies as well as in cultured fibroblasts. Metabolic testing isnormal.
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 theirvisual and motor problems as well as dysarthria. Hormonal replacement therapy isneeded if hypogonadism is present.
The differential diagnosis includes: MSS with chylomicronemia (607692), congenitalcataracts, facial dysmorphism, and neuropathy (604168), mitochondrial disorders, andthe carbohydrate deficient glycoprotein syndromes.