X-vezani oblici Charcot - Marie - Toothove bolesti u pedijatriji

master's thesis

• Title (english): X-linked Charcot-Marie-Tooth disease in pediatrics
• Author: Nikola Kos
• Mentor: Nina Barišić (mentor)
• Committee member: Irena Senečić-Čala (predsjednik povjerenstva)
• Committee member: Marija Jelušić (član povjerenstva)
• Committee member: Nina Barišić (član povjerenstva)
• Granter: University of Zagreb; School of Medicine; (Department of Pediatrics); Zagreb
• Defense date and country: 2014-07-15, Croatia
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Clinical Medical Sciences; Pediatrics

Abstract

Charcot-Marie-Toothova bolest (CMT) je klinički genetski i elektrofiziološki vrlo heterogena skupina nasljednih bolesti perifernih živaca. X-vezani oblik CMT (CMTX1) je drugi najčešći uzrok demijelinizirajućeg oblika CMT. Opisano je 6 tipova CMTX (CMTX1-CMTX6). CMTX1 je najčešća među njima i uzrokovana je mutacijom GJB1 gena čija je uloga kodiranje koneksina 32 (Cx32). Mijelinizirajuće Schwannove stanice ispoljavaju Cx32 koji sudjeluje u formiranju tijesnih spojeva među slojevima mijelina. Tijesni spojevi građeni od molekula Cx32 imaju važnu ulogu u homeostazi mijeliniziranih aksona. CMTX1 je X-vezani dominantni oblik CMT sa znakovima gubitka mijelina i aksona. Muškarci razvijaju umjerene do teške simptome, dok su žene heterozigoti blaže zahvaćene ili čak asimptomatske. Simptomi se razvijaju u kasnom djetinjstvu, kod dječaka nakon pete godine, a kod djevojčica nešto kasnije. Klinička slika je karakterizirana progresivnom atrofijom distalnih skupina mišića, slabošću, gubitkom osjeta, arefleksijom, deformacijama kostiju stopala (ekskavirano stopalo), skoliozom te kontrakturama. Kliničke manifestacije obično uključuju i atrofiju mišića šake, ponajprije tenarnih mišića. Oligodendrociti također ispoljavaju Cx32 pa se kod nekih pacijenata bolest manifestira znakovima zahvaćanja središnjeg živčanog sustava ili gubitka sluha. Bolesnici s CMTX1 tipično se prezentiraju s umjereno usporenom brzinom provođenja živaca. Budući da dosad nije otkrivena molekularna terapija bolesti, glavni terapijski pristup jest simptomatski, uz dugoročno multidisciplinarno praćenje bolesnika od strane dječjeg neurologa, fizijatra, ortopeda, kirurga i psihijatra.

Abstract (english)

Charcot-Marie-Tooth (CMT) is a genetically, clinically and electrophysiologically heterogeneous group of inherited disorders of the peripheral nervous system. The X-linked form of Charcot-Marie-Tooth disease (CMTX1) is the second most common cause of a demyelinating type of CMT. There are 6 types of CMTX (CMTX1-CMTX6). CMTX1 is the most common one, and is caused by mutations in the GJB1 gene which encodes connexin 32 (Cx32). Myelinating Schwann cells express Cx32, which likely forms gap junctions between the layers of myelin sheath. Gap junctions formed by Cx32 play an important role in the homeostasis of myelinated axons. CMTX1 is an X-linked dominant type of CMT with both demyelinating and axonal features. Affected males have moderate-to-severe symptoms, whereas heterozygous females are usually mildly affected, or even asymptomatic. Symptoms develop in late childhood, usually after the age of five in males, and later in affected females. The clinical phenotype is characterized by progressive distal muscle atrophy, weakness, sensory loss, areflexia, skeletal deformities (high arched feet), scoliosis and contractures. Clinical features also include involvement of hand muscles with pronounced atrophy, particularly affecting thenar muscles. Oligodendrocytes also express Cx32, so several patients have manifestations of central nervous system involvement or hearing impairment. Patients with CMTX1 typically manifest intermediate slowing of nerve conduction velocity (NCV). There is no known molecular-based treatments for CMTX1. Treatment is symptomatic and affected individuals are often evaluated and managed by a team of children neurologists, physiatrists, ortopedic surgeons and psychiatrist.

• Keywords: Charcot-Marie-Toothova bolest; neuropatija; X vezano; koneksin 32; tijesni spoj
• Keywords (english): Charcot-Marie-Tooth disease; neuropathy; X-linked; connexin 32; gap junctions
• Language: croatian
• URN:NBN: urn:nbn:hr:105:457666
• Study programme: Title: Medicine; Study programme type: university; Study level: integrated undergraduate and graduate; Academic / professional title: doktor/doktorica medicine (doktor/doktorica medicine)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Open access
• Created on: 2016-03-10 10:02:50