MORPHOLOGYSkeletal abnormalities arethemostobviousfeatureofMarfansyndrome.Patientshaveaslender,elongatedhabituswithabnormallylonglegs,arms,andfingers(arachnodactyly);ahigh-archedpalate;andhyperextensibilityofjoints.Avarietyofspinaldeformities,suchasseverekyphoscoliosis,maybepresent.Thechestisdeformed,exhibitingeitherpectusexcavatum(i.e.,deeplydepressedsternum)orapigeon-breastdeformity.Themostcharacteristicocular change isbilateraldislocation,orsubluxation,ofthelenssecondarytoweaknessofitssuspensoryligaments(ectopia lentis). Ectopialentis,particularlyifbilateral,ishighlyspecificforMarfansyndromeandstronglysuggeststhediagnosis.Mostserious,however,istheinvolvementofthecardiovascular system. Fragmentationoftheelasticfibersinthetunicamediaoftheaortapredisposesaffectedpatientstoaneurysmaldilationandaorticdissection(Chapter10).Thesechanges,calledcystic medionecrosis, arenotspecificforMarfansyndrome;similarlesionsoccurinhypertensionandwithaging.Lossofmedialsupportcausesdilationoftheaorticvalvering,givingrisetoaorticincompetence.Thecardiacvalves,especiallythemitralvalve,maybeexcessivelydistensibleandregurgitant(floppy valve syndrome), givingrisetomitralvalveprolapseandcongestivecardiacfailure(Chapter11).Aorticruptureisthemostcommoncauseofdeathandmayoccuratanyage.Lessfrequently,cardiacfailureistheterminalevent.
AlthoughthelesionsdescribedaretypicalofMarfansyndrome,theyarenotseeninallcases.Thereismuchvariationinclinicalexpression,andsomepatientsmayexhibitpredominantlycardiovascularlesionswithminimalskeletalandocularchanges.ItisbelievedthatthevariableexpressivityisrelatedtodifferentmutationsintheFBN1 gene.
MarfansyndromeiscausedbyamutationintheFBN1 geneencodingfibrillin,whichisrequiredforstructuralintegrityofconnectivetissuesandactivationofTGF-β.
Themajortissuesaffectedaretheskeleton,eyes,andcardiovascularsystem.
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Clinicalfeaturesmayincludetallstature,longfingers,bilateralsubluxationoflens,mitralvalveprolapse,aorticaneurysm,andaorticdissection.
PreventionofcardiovasculardisesaeinvolvestheuseofdrugsthatlowerbloodpressureandinhibitTGF-β signaling.
Ehlers-Danlos syndromes (EDSs) are a group of diseases characterized by defects in collagen synthesis or structure. All are single-gene disorders, but the mode of inheritance encompasses both autosomal dominant and recessive patterns. There are approximately 30 distinct types of collagen; all have characteristic tissue distributions and are the products of different genes. To some extent, the clinical heterogeneity of EDS can be explained by mutations in different collagen genes.
At least six clinical and genetic variants of EDS are recognized. Because defective collagen is the basis for these disorders, certain clinical features are common to all variants.
Tissues rich in collagen, such as skin, ligaments, and joints, frequently are affected in most variants of EDS. Because the abnormal collagen fibers lack adequate tensile strength, joints are hypermobile. These features permit grotesque contortions, such as bending the thumb backward to touch the forearm and bending the knee upward to create almost a right angle. Indeed, it is believed that most contortionists have some form of EDS; however, a predisposition to joint dislocation is one of the prices paid for this virtuosity.