Central core disease

{{Short description|Autosomal dominant genetic disorder}} {{Infobox medical condition (new) | name = Central Core Disease | synonyms = Central core myopathy | image = Cell_sample_of_muscle_tissue_with_central_core_disease_(stained_for_contrast).jpg | caption = Histopathologic appearance of typical central core disease: NADH-TR, transverse section from the rectus femoris. Marked predominance of dark staining, high oxidative type 1 fibres with cores affecting the majority of fibres. Cores are typically well demarcated and centrally located (→), but may occasionally be multiple and of eccentric location. | pronounce = | field = | geneReviews = | symptoms = | complications = | onset = | duration = | types = | causes = | risks = | diagnosis = | differential = | prevention = | treatment = | medication = | prognosis = | frequency = | deaths = }} '''Central core disease''' ('''CCD'''), also known as '''central core myopathy''', is an autosomal dominant inherited<ref name=ryr>{{cite journal |pmid=12124989 |date=August 2002 |author1=Robinson, Rl |author2=Brooks, C |author3=Brown, Sl |author4=Ellis, Fr |author5=Halsall, Pj |author6=Quinnell, Rj |author7=Shaw, Ma |author8=Hopkins, Pm |title=RYR1 mutations causing central core disease are associated with more severe malignant hyperthermia in vitro contracture test phenotypes |volume=20 |issue=2 |pages=88–97 |doi=10.1002/humu.10098 |journal=Human Mutation|s2cid=21497303 |doi-access=free }}</ref> muscle disorder present from birth that negatively affects the skeletal muscles. It was first described by Shy and Magee in 1956.<ref name=Quinlivan>{{cite journal |author=Quinlivan RM |title=Central core disease: clinical, pathological, and genetic features |journal=Arch. Dis. Child. |volume=88 |issue=12 |pages=1051–5 |year=2003 |pmid=14670767 |url= |doi=10.1136/adc.88.12.1051 |pmc=1719384 |name-list-style=vanc|author2=Muller CR |author3=Davis M |display-authors=3 |last4=Laing |first4=NG |last5=Evans |first5=GA |last6=Dwyer |first6=J |last7=Dove |first7=J |last8=Roberts |first8=AP |last9=Sewry |first9=CA}}</ref><ref>{{cite journal |vauthors=Magee KR, Shy GM |title=A new congenital non-progressive myopathy |journal=Brain |volume=79 |issue=4 |pages=610–21 |year=1956 |pmid=13396066 |doi=10.1093/brain/79.4.610|citeseerx=10.1.1.1026.496 }}</ref> It is characterized by the appearance of the myofibril under the microscope.<ref>{{DorlandsDict|three/000030637|central core disease}}</ref>

==Signs and symptoms== The symptoms of CCD are variable, but usually involve hypotonia (decreased muscle tone) at birth, mild delay in child development (highly variable between cases), weakness of the facial muscles, and skeletal malformations such as scoliosis and hip dislocation.<ref name=Quinlivan/>

CCD is usually diagnosed in infancy or childhood, but some patients remain asymptomatic until adulthood to middle age.<ref>{{cite journal |last1=Talwalkar |first1=SS |last2=Parker |first2=JR |last3=Heffner |first3=RR |last4=Parker |first4=JC |title=Adult central core disease. Clinical, histologic and genetic aspects: case report and review of the literature. |journal=Clin Neuropathol |date=2006 |volume=25 |issue=4 |pages=180–4 |pmid=16866299}}</ref>

==Pathophysiology== [[Image:Autosomal dominant - en.svg|thumb|right|Central core disease has an autosomal dominant pattern of inheritance.]]

Central core disease is inherited in an autosomal dominant fashion. Most cases have demonstrable mutations in the ryanodine receptor type 1 (''RYR1'') gene,<ref name=ryr/> which are often ''de novo'' (newly developed). People with CCD are at increased risk for developing malignant hyperthermia (MH) when receiving general anesthesia.<ref name=Quinlivan/>

==Diagnosis== The diagnosis is made based on the combination of typical symptoms and the appearance on biopsy (tissue sample) from muscle. The name derives from the typical appearance of the biopsy on light microscopy, where the muscle cells have cores that are devoid of mitochondria and specific enzymes.<ref name=Quinlivan/>

Respiratory insufficiency develops in a small proportion of cases. Creatine kinase tend to be normal and electromyography (EMG) shows short duration, short amplitude motor unit action potentials.<ref name=Quinlivan/>

==Treatment== There is no specific treatment for central core disease. Certain triggering anesthetics must be avoided, and relatives should be screened for ''RYR1'' mutations that cause malignant hyperthermia.<ref name=Quinlivan/>

Research has shown that some patients may benefit from treatment with oral salbutamol.<ref>{{Cite web |title=Use of Salbutamol in Neuromuscular conditions |url=https://www.cuh.nhs.uk/patient-information/use-of-salbutamol-in-neuromuscular-conditions/ |access-date=2023-08-26 |website=Cambridge University Hospitals |language=en-GB}}</ref><ref>{{Cite journal |last1=Messina |first1=S. |last2=Hartley |first2=L. |last3=Main |first3=M. |last4=Kinali |first4=M. |last5=Jungbluth |first5=H. |last6=Muntoni |first6=F. |last7=Mercuri |first7=E. |date=October 2004 |title=Pilot trial of salbutamol in central core and multi-minicore diseases |journal=Neuropediatrics |volume=35 |issue=5 |pages=262–266 |doi=10.1055/s-2004-821173 |issn=0174-304X |pmid=15534757|s2cid=260238342 }}</ref>

==References== {{reflist}} == External links == {{Medical resources | DiseasesDB =  | ICD10 = {{ICD10|G|71|2|g|70}} | ICD9 = {{ICD9|359.0}} | OMIM = 117000 | eMedicineSubj = neuro | eMedicineTopic = 76 | GeneReviewsNBK = NBK1391 | MeshID = D020512 | Orphanet = 597 }} {{Diseases of myoneural junction and muscle}} {{Channelopathy}}

{{DEFAULTSORT:Central Core Disease}} Category:Myoneural junction and neuromuscular diseases Category:Autosomal dominant disorders