{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T04:51:33Z","timestamp":1789015893701,"version":"build-2803163510"},"reference-count":14,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2020,11,11]],"date-time":"2020-11-11T00:00:00Z","timestamp":1605052800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2021,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Klippel\u2010Feil syndrome 4 (KFS4; MIM# 616549) is an autosomal recessive disorder caused by biallelic pathogenic variants in <jats:italic>MYO18B<\/jats:italic> and comprises, in addition to Klippel\u2010Feil anomaly (KFA), nemaline myopathy, facial dysmorphism, and short stature. We aim to outline the natural history of KFS4 and provide an updated description of its clinical, radiological, laboratory, and molecular findings. We comprehensively analyzed the medical records of 6 Saudi and 1 American patients (including 5 previously unpublished cases) with a molecularly confirmed diagnosis of KFS4. All patients had myopathy of varying severity that followed a slowly progressive or non\u2010progressive course, affecting primarily the proximal musculature of the lower limb although hand involvement with distal arthrogryposis and abnormal interphalangeal creases was also observed. KFA and characteristic dysmorphic features, including ptosis and bulbous nose, were observed in all but two patients. The causal <jats:italic>MYO18B<\/jats:italic> variants were a founder NM_032608.5:c.6905C&gt;A; p.(Ser2302*) variant in the Saudi patients (P1\u2010P6) and a novel <jats:italic>MYO18B<\/jats:italic> homozygous variant (c.6660_6670del;p.[Arg2220Serfs*74]) in the American Caucasian patient (P7). We report the phenotypic and genetic findings in seven patients with KFS4. We describe the natural history of this disease, confirm myopathy as a universal feature and describe its pattern and progression, and note interesting differences between the phenotypes observed in patients with KFA and those without.<\/jats:p>","DOI":"10.1002\/ajmg.a.61957","type":"journal-article","created":{"date-parts":[[2020,11,12]],"date-time":"2020-11-12T07:29:03Z","timestamp":1605166143000},"page":"370-376","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Further delineation of <scp><i>MYO18B<\/i><\/scp>\u2010related autosomal recessive <scp>Klippel\u2010Feil<\/scp> syndrome with myopathy and facial dysmorphism"],"prefix":"10.1002","volume":"185","author":[{"given":"Fadie D.","family":"Altuame","sequence":"first","affiliation":[{"name":"College of Medicine Alfaisal University  Riyadh Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chad","family":"Haldeman\u2010Englert","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics Mission Fullerton Genetics Center  Asheville North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edward","family":"Cupler","sequence":"additional","affiliation":[{"name":"Department of Neurosciences King Faisal Specialist Hospital and Research Center  Jeddah Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammad A.","family":"Al Muhaizea","sequence":"additional","affiliation":[{"name":"Department of Neurosciences King Faisal Specialist Hospital and Research Center  Riyadh Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hamad I.","family":"Al\u2010Zaidan","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics King Faisal Specialist Hospital and Research Center  Riyadh Saudi 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