{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T00:29:45Z","timestamp":1792542585866,"version":"4.5.0"},"reference-count":40,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2014,10,22]],"date-time":"2014-10-22T00:00:00Z","timestamp":1413936000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2014,12]]},"abstract":"<jats:sec><jats:label\/><jats:p>Joint hypermobility syndrome (JHS) and Ehlers\u2010Danlos syndrome, hypermobility type (EDS\u2010HT) are two markedly overlapping heritable connective tissue disorders. The cumulative frequency of JHS and EDS\u2010HT seems high, but their recognition remains an exclusion diagnosis based on different sets of diagnostic criteria. Although proposed by a panel of experts, clinical identity between JHS and EDS\u2010HT is still a matter of debate due to unknown molecular basis. We present 23 families with three or more individuals with a diagnosis of JHS and\/or EDS\u2010HT. Rough data from the 82 individuals were used to assess the frequency of major and minor criteria, as well as selected additional features. A series of statistical tools were applied to assess intrafamilial and interfamilial variability, emphasizing intergenerational, and intersex differences. This study demonstrates marked heterogeneity within and between families in terms of agreement of available diagnostic criteria. In 21 pedigrees affected individuals belong to two or three phenotypic sub\u2010categories among JHS, EDS\u2010HT, and JHS\u2009+\u2009EDS\u2010HT overlap. Intergenerational analysis depicts a progressive shifting, also within the same pedigree, from EDS\u2010HT in childhood, to JHS\u2009+\u2009EDS\u2010HT in early adulthood and JHS later in life. Female\u2010male ratio is 2.1:1, which results lower than previously observed in unselected patients' cohorts. In these pedigrees, JHS, EDS\u2010HT, and JHS\u2009+\u2009EDS\u2010HT segregate as a single dominant trait with complete penetrance, variable expressivity, and a markedly evolving phenotype. This study represents a formal demonstration that EDS\u2010HT and JHS contitute the same clinical entity, and likely share the same genetic background, at least, in familial cases. \u00a9 2014 Wiley Periodicals, Inc.<\/jats:p><\/jats:sec>","DOI":"10.1002\/ajmg.a.36805","type":"journal-article","created":{"date-parts":[[2014,10,22]],"date-time":"2014-10-22T17:51:59Z","timestamp":1414000319000},"page":"3010-3020","source":"Crossref","is-referenced-by-count":73,"title":["Nosology and inheritance pattern(s) of joint hypermobility syndrome and Ehlers\u2010Danlos syndrome, hypermobility type: A study of intrafamilial and interfamilial variability in 23 Italian pedigrees"],"prefix":"10.1002","volume":"164","author":[{"given":"Marco","family":"Castori","sequence":"first","affiliation":[{"name":"Division of Medical Genetics Department of Molecular Medicine Sapienza University San Camillo\u2010Forlanini Hospital Rome 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of Brescia Brescia Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvia","family":"Morlino","sequence":"additional","affiliation":[{"name":"Division of Medical Genetics Department of Molecular Medicine Sapienza University San Camillo\u2010Forlanini Hospital Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicola","family":"Chiarelli","sequence":"additional","affiliation":[{"name":"Division of Biology and Genetics Department of Molecular and Translational Medicine School of Medicine University of Brescia Brescia Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia","family":"Celletti","sequence":"additional","affiliation":[{"name":"Division of Physical Therapy and Rehabilitation Department of Orthopedic Sciences Sapienza University Umberto I University Hospital Rome 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