View source for Distal myopathy

{{Infobox medical condition (new)
| name            = Distal myopathy
| synonyms        = Distal muscular dystrophy
| image           = Body Diagram.png
| caption         = Red depicts the preferentially affected areas in distal myopathy.
| image_size      = 125
| pronounce       =
| field           = [[Neurology]], [[neuromuscular medicine]]
| symptoms        = Weakness of hands and/or feet
| complications   = Cardiomyopathy
| onset           = Variable
| duration        = Lifetime
| types           = Classic, myofibrillar myopathy, other
| causes          = Genetic mutation of various genes
| risks           =
| diagnosis       = Genetic testing, muscle biopsy
| differential    =
| prevention      =
| treatment       =
| medication      =
| prognosis       =
| frequency       = Rare
| deaths          =
}}

'''Distal myopathy'''  is a group of rare genetic disorders that cause muscle damage and weakness, predominantly in the hands and/or feet. Mutation of many different genes can be causative. Many types involve [[dysferlin]].<ref name="pmid16310593">{{cite journal  |vauthors=Murakami N, Sakuta R, Takahashi E, etal |title=Early onset distal muscular dystrophy with normal dysferlin expression |journal=Brain Dev. |volume=27 |issue=8 |pages=589–91 |date=December 2005 |pmid=16310593 |doi=10.1016/j.braindev.2005.02.002 |s2cid=28957231 }}</ref>

==Signs and symptoms==
All of the different types affect different regions of the extremities and can show up as early as 5 years of age to as late as 50 years old. Distal myopathy has slow progress therefore the patient may not know that they have it until they are in their late 40s or 50s.{{citation needed|date=May 2016}}

Miyoshi myopathy affects the posterior muscles of the lower leg, more so than the anterior muscles of the lower leg.<ref name="pmid14762596">{{cite journal |vauthors=Soares CN, de Freitas MR, Nascimento OJ, da Silva LF, de Freitas AR, Werneck LC |title=Myopathy of distal lower limbs: the clinical variant of Miyoshi |journal=Arq Neuropsiquiatr |volume=61 |issue=4 |pages=946–9 |date=December 2003 |pmid=14762596 |doi= 10.1590/S0004-282X2003000600011|doi-access=free }}</ref><ref>{{cite journal|last1=Aoki|first1=Masashi|title=Dysferlinopathy|journal=GeneReviews|date=1 January 1993|pmid=20301480|url=https://www.ncbi.nlm.nih.gov/books/NBK1303/|access-date=10 May 2016}}</ref>

==Cause==
[[File:4ihb pdb.png|thumb|DYSF]]
The cause of this myopathy is very hard to determine because it can be a mutation in any of at least eight genes and not all are known yet. These mutations can be inherited from one parent, autosomal dominant, or from both parents, autosomal recessive. There are eight known types of distal myopathy.{{citation needed|date=May 2016}}

===Types===
{| class="wikitable" style="border: 1px none white;"
|+ Classic distal muscular dystrophies
|-
! Type
! Eponym
! Inheritance
! [[OMIM]]
! Gene
! Locus
! Gene also implicated in:

|-
| Late adult-onset type 1<ref name="Saperstein2001Review" />
| Welander
| AD<ref name="Dimachkie2014Review" />
| {{OMIM|604454||none}}
| [[TIA1]]<ref name="pmid23401021">{{cite journal |vauthors=Hackman P, Sarparanta J, Lehtinen S, Vihola A, Evilä A, Jonson PH, Luque H, Kere J, Screen M, Chinnery PF, Åhlberg G, Edsröm L, Udd B  |title=Welander Distal Myopathy Is Caused by a Mutation in the RNA-Binding Protein TIA1|journal=Annals of Neurology |volume=73 |issue=4 |pages=500–509 |date=January 2013 |pmid=23401021 |doi=10.1002/ana.23831|s2cid=13908127 }}</ref>
| 2p13<ref name="pmid12836053">{{cite journal |vauthors=von Tell D, Bruder CE, Anderson LV, Anvret M, Ahlberg G |title=Refined mapping of the Welander distal myopathy region on chromosome 2p13 positions the new candidate region telomeric of the DYSF locus |journal=Neurogenetics |volume=4 |issue=4 |pages=173–7 |date=August 2003 |pmid=12836053 |doi=10.1007/s10048-003-0154-z|s2cid=27539044 }}</ref>
|
|-
| Late adult-onset type 2a<ref name="Dimachkie2014Review">{{cite journal |last1=Dimachkie |first1=MM |last2=Barohn |first2=RJ |title=Distal myopathies. |journal=Neurologic Clinics |date=August 2014 |volume=32 |issue=3 |pages=817-42, x |doi=10.1016/j.ncl.2014.04.004 |pmid=25037092|pmc=4109660 }}</ref> - Finnish (tibial)
| Udd
| AD<ref name="Dimachkie2014Review" />
| {{OMIM|600334||none}}
| ''[[TTN (gene)|TTN]]''<ref name="Dimachkie2014Review" />
| 2q31.2
|
|-
| Late adult-onset type 2b<ref name="Dimachkie2014Review" />
| Markesbery–Griggs
| AD<ref name="Udd2011Review" />
|
| ''[[LDB3|ZASP]]''<ref name="Dimachkie2014Review" />
| 10q23.2
|
|-
| Early adult-onset type 1<ref name="Saperstein2001Review">{{cite journal |last1=Saperstein |first1=DS |last2=Amato |first2=AA |last3=Barohn |first3=RJ |title=Clinical and genetic aspects of distal myopathies. |journal=Muscle & Nerve |date=November 2001 |volume=24 |issue=11 |pages=1440–50 |doi=10.1002/mus.1167 |pmid=11745945|s2cid=26573674 }}</ref>
| Nonaka
| AR<ref name="Dimachkie2014Review" />
| {{OMIM|605820||none}}
| ''[[GNE (gene)|GNE]]''<ref name="Dimachkie2014Review" />
| 9p13.3
|
|-
| style='border-style: solid solid dashed solid;'  | Early adult-onset type 2<ref name="Saperstein2001Review" />
| style='border-style: none  solid dashed solid;'  | Miyoshi
| rowspan="2"| AR<ref name="Dimachkie2014Review" />
| {{OMIM|254130||none}}
| rowspan="2" |[[DYSF]]<ref name="Dimachkie2014Review" />
| rowspan="2" |[[Locus (genetics)|2p13.3-p13.1]]
| style='border-style: solid solid dashed solid;'  |[[limb-girdle muscular dystrophy]] type 2B.<ref name="pmid10787109">{{cite journal |author=Illa I |title=Distal myopathies |journal=J. Neurol. |volume=247 |issue=3 |pages=169–74 |date=March 2000 |pmid=10787109 |doi=10.1007/s004150050557 |s2cid=39723106 |url=http://link.springer.de/link/service/journals/00415/bibs/0247003/02470169.htm |archive-url=https://archive.today/20130213012235/http://link.springer.de/link/service/journals/00415/bibs/0247003/02470169.htm |url-status=dead |archive-date=2013-02-13 |url-access=subscription }}</ref>
|-
| style='border-style: none solid solid solid;'  |Distal myopathy with anterior tibial onset (DMAT)<ref name="Liu1998DMAT">{{cite journal |last1=Liu |first1=J |last2=Aoki |first2=M |last3=Illa |first3=I |last4=Wu |first4=C |last5=Fardeau |first5=M |last6=Angelini |first6=C |last7=Serrano |first7=C |last8=Urtizberea |first8=JA |last9=Hentati |first9=F |last10=Hamida |first10=MB |last11=Bohlega |first11=S |last12=Culper |first12=EJ |last13=Amato |first13=AA |last14=Bossie |first14=K |last15=Oeltjen |first15=J |last16=Bejaoui |first16=K |last17=McKenna-Yasek |first17=D |last18=Hosler |first18=BA |last19=Schurr |first19=E |last20=Arahata |first20=K |last21=de Jong |first21=PJ |last22=Brown RH |first22=Jr |title=Dysferlin, a novel skeletal muscle gene, is mutated in Miyoshi myopathy and limb girdle muscular dystrophy. |journal=Nature Genetics |date=September 1998 |volume=20 |issue=1 |pages=31–6 |doi=10.1038/1682 |pmid=9731526|s2cid=12018395 }}</ref><ref name="Illa2001DMAT">{{cite journal |last1=Illa |first1=I |last2=Serrano-Munuera |first2=C |last3=Gallardo |first3=E |last4=Lasa |first4=A |last5=Rojas-García |first5=R |last6=Palmer |first6=J |last7=Gallano |first7=P |last8=Baiget |first8=M |last9=Matsuda |first9=C |last10=Brown |first10=RH |title=Distal anterior compartment myopathy: a dysferlin mutation causing a new muscular dystrophy phenotype. |journal=Annals of Neurology |date=January 2001 |volume=49 |issue=1 |pages=130–4 |doi=10.1002/1531-8249(200101)49:1<130::AID-ANA22>3.0.CO;2-0 |pmid=11198284}}</ref>
| style='border-style: none solid solid solid;'  |
| {{OMIM|606768||none}}
| style='border-style: none solid solid solid;' | DMAT can be considered a variant of Miyoshi.
|-
| Early adult-onset type 3<ref name="Saperstein2001Review" />
| Laing (Gower)
| AD<ref name="Dimachkie2014Review" />
| {{OMIM|160500||none}}
| ''[[MYH7]]''<ref name="Dimachkie2014Review" />
| 14q11.2
|
|-
| colspan="7" style="background: white; border-style: none none none none;" | AD = [[autosomal dominant]]; AR = [[autosomal recessive]]
|}

{| class="wikitable" style="border: 1px none white;"
|+ Myofibrillar myopathies classifiable as distal myopathy
|-
! Type
! Eponym
! Inheritance
! [[OMIM]]
! Gene
! Locus
! Gene also implicated in:
|-
| Desmin — adult onset (MFM1)<ref name="Dimachkie2014Review" />
Hereditary inclusion-body myositis type 1<ref name="Dimachkie2014Review" />
|
| AD
|
|
|
|
|-
| αB-crystallin — early - mid adult (MFM2)<ref name="Dimachkie2014Review" />
|
| AD
|
|
|
|
|-
| ZASP— late adult (MFM4)<ref name="Dimachkie2014Review" />
|
| AD
|
|
|
|
|-
| Scapuloperoneal<ref name="Dimachkie2014Review" />
|
| AD
|
|
|
|
|-
| colspan="7" style="background: white; border-style: none none none none;" | MFM = myofibrillary myopathy; AD = [[autosomal dominant]]; AR = [[autosomal recessive]]
|}
{| class="wikitable" style="border: 1px none white;"
|+ Other distal muscular dystrophies
|-
! Type
! Eponym
! Inheritance
! [[OMIM]]
! Gene
! Locus
! Gene also implicated in:

|-
| Distal myopathy with vocal cord and pharyngeal weakness<ref name="Saperstein2001Review" />
|
| AD<ref name="Dimachkie2014Review" />
| {{OMIM|606070||none}}
| ''[[MATR3]]''<ref name="Dimachkie2014Review" />
| 5q31<ref name="Dimachkie2014Review" />
| [[Amyotrophic lateral sclerosis]] 21 (ALS21). One study suggests that all cases are ALS, justifying reclassification.<ref name="Johnson2014ALS">{{cite journal |last1=Johnson |first1=JO |last2=Pioro |first2=EP |last3=Boehringer |first3=A |last4=Chia |first4=R |last5=Feit |first5=H |last6=Renton |first6=AE |last7=Pliner |first7=HA |last8=Abramzon |first8=Y |last9=Marangi |first9=G |last10=Winborn |first10=BJ |last11=Gibbs |first11=JR |last12=Nalls |first12=MA |last13=Morgan |first13=S |last14=Shoai |first14=M |last15=Hardy |first15=J |last16=Pittman |first16=A |last17=Orrell |first17=RW |last18=Malaspina |first18=A |last19=Sidle |first19=KC |last20=Fratta |first20=P |last21=Harms |first21=MB |last22=Baloh |first22=RH |last23=Pestronk |first23=A |last24=Weihl |first24=CC |last25=Rogaeva |first25=E |last26=Zinman |first26=L |last27=Drory |first27=VE |last28=Borghero |first28=G |last29=Mora |first29=G |last30=Calvo |first30=A |last31=Rothstein |first31=JD |last32=ITALSGEN. |last33=Drepper |first33=C |last34=Sendtner |first34=M |last35=Singleton |first35=AB |last36=Taylor |first36=JP |last37=Cookson |first37=MR |last38=Restagno |first38=G |last39=Sabatelli |first39=M |last40=Bowser |first40=R |last41=Chiò |first41=A |last42=Traynor |first42=BJ |title=Mutations in the Matrin 3 gene cause familial amyotrophic lateral sclerosis. |journal=Nature Neuroscience |date=May 2014 |volume=17 |issue=5 |pages=664–666 |doi=10.1038/nn.3688 |pmid=24686783|pmc=4000579 }}</ref>
|}

==Diagnosis==
In terms of diagnosis, Vocal cord and pharyngeal distal myopathy should be assessed via serum CK levels, as well as [[muscle biopsy]] of the individual suspected of being afflicted with this condition<ref>{{cite book |chapter=Distal muscular dystrophies |series=Handbook of Clinical Neurology |date=1 January 2011 |volume=101 |pages=239–262 |doi=10.1016/B978-0-08-045031-5.00016-5 |pmid=21496636 |language=en |issn=0072-9752|last1=Udd |first1=Bjarne |title=Muscular Dystrophies |isbn=9780080450315 }}{{Subscription or libraries|sentence|via=[[ScienceDirect]]}}</ref>

==Management==
As of 2011, no disease modifying treatments are known.<ref name="Udd2011Review">{{cite book |last1=Udd |first1=B |chapter=Distal muscular dystrophies |title=Muscular Dystrophies |series=Handbook of Clinical Neurology |date=2011 |volume=101 |pages=239–62 |doi=10.1016/B978-0-08-045031-5.00016-5 |pmid=21496636|isbn=9780080450315 }}</ref> Foot drop can be managed with ankle-foot orthoses or surgical [[tendon transfer]],<ref name="Udd2011Review" /> in which the [[tibialis posterior muscle]] is repurposed to function as a [[tibialis anterior muscle]]. In select types of distal myopathy, evaluation of the heart may be indicated.<ref name="Udd2011Review" /> Scoliosis and contractures can be surgically managed.<ref name="Udd2011Review" /> In 2024 a drug to treat distal myopathy was approved in Japan.<ref>{{cite news |title=Persistence pays off with approval of distal myopathy drug |url=https://www.japantimes.co.jp/news/2024/05/20/japan/science-health/distal-myopathy-drug-approved/ |publisher=The Japan Times |date=20 May 2024}}</ref>

==References==
{{Reflist|32em}}

==Further reading==
* {{cite journal|last1=Udd|first1=Bjarne|title=Molecular biology of distal muscular dystrophies—Sarcomeric proteins on top|journal=Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease|date=February 2007|volume=1772|issue=2|pages=145–158|doi=10.1016/j.bbadis.2006.08.005|pmid=17029922|doi-access=free}}

== External links ==
{{Medical resources
| DiseasesDB      = 31977
| ICD10           = {{ICD10|G|71|0|g|70}}
| ICD9            = {{ICD9|359.1}}
| ICDO            =
| OMIM            = 254130
| OMIM_mult       = {{OMIM|604454||none}} {{OMIM|606768||none}}
| MedlinePlus     =
| eMedicineSubj   =
| eMedicineTopic  =
| MeshID          = D049310
| GeneReviewsNBK  = NBK1303
| GeneReviewsName = Dysferlinopathy
| SNOMED CT       = 58795000
}}

{{Muscular Dystrophy}}
{{Diseases of myoneural junction and muscle}}
{{Other cell membrane protein disorders}}
[[Category:Muscular dystrophy]]