{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,10]],"date-time":"2026-04-10T17:24:02Z","timestamp":1775841842487,"version":"3.50.1"},"reference-count":13,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2014,11,26]],"date-time":"2014-11-26T00:00:00Z","timestamp":1416960000000},"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":[[2015,2]]},"abstract":"<jats:sec><jats:label\/><jats:p>Menkes disease (MD; OMIM 309400) is an X\u2010linked, neurodegenerative disorder resulting from deficient activity of copper\u2010dependent enzymes and caused by alterations in the <jats:italic>APT7A<\/jats:italic> gene. In its classic form, it manifests in boys with hypotonia, seizures, skin and joint laxity, hair twisting (<jats:italic>pili torti<\/jats:italic>), cerebrovascular tortuosity, and bladder diverticulae. Menkes disease phenotypes have been reported in females with X; autosome translocations\u2010 disrupting <jats:italic>ATP7A<\/jats:italic> gene function\u2010 or <jats:italic>ATP7A<\/jats:italic> gene alterations. Those females manifest variable clinical findings, some of which, such as <jats:italic>pili torti<\/jats:italic>, seizure presence and\/or age of onset, cerebrovascular tortuosity, degree of intellectual disability, and bladder divericulae are largely under\u2010reported and under\u2010studied. Here, we report on three females with Menkes disease and variant phenotypes, sharing characteristic features, one with classic Menkes disease and two with Menkes disease variants. We conclude that Menkes disease in females manifests with a variable spectrum of clinical findings but a few are uniformly present such as neurodevelopmental disability, hypotonia, and connective tissue findings. Others, such as seizures, cerebral atrophy, and cerebrovascular tortuosity may be present but are under\u2010reported and under\u2010 studied. We propose that the diagnosis of Menkes disease or variants in females with suspicious clinical findings is an important one to consider as early treatment with parenteral copper may be considered. The effect of this treatment on the disease course in females with MD is unknown and remains to be seen. \u00a9 2014 Wiley Periodicals, Inc.<\/jats:p><\/jats:sec>","DOI":"10.1002\/ajmg.a.36853","type":"journal-article","created":{"date-parts":[[2015,1,21]],"date-time":"2015-01-21T12:49:18Z","timestamp":1421844558000},"page":"417-420","source":"Crossref","is-referenced-by-count":34,"title":["Menkes disease in affected females: The clinical disease spectrum"],"prefix":"10.1002","volume":"167","author":[{"given":"Patroula","family":"Smpokou","sequence":"first","affiliation":[{"name":"Division of Genetics &amp; Metabolism Children's National Health System Washington District of Columbia"},{"name":"The George Washington University School of Medicine and Health Sciences Washington District of Columbia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Monisha","family":"Samanta","sequence":"additional","affiliation":[{"name":"Division of Genetics &amp; Metabolism Children's National Health System Washington District of Columbia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gerard T.","family":"Berry","sequence":"additional","affiliation":[{"name":"Division of Genetics Boston Children's Hospital Boston Massachusetts"},{"name":"Harvard Medical School Boston Massachusetts"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Leah","family":"Hecht","sequence":"additional","affiliation":[{"name":"Division of Genetics Boston Children's Hospital Boston Massachusetts"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elizabeth C.","family":"Engle","sequence":"additional","affiliation":[{"name":"Harvard Medical School Boston Massachusetts"},{"name":"Department of Neurology Boston Children's Hospital Boston Massachusetts"},{"name":"Howard Hughes Medical Institute Bethesda Maryland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Uta","family":"Lichter\u2010Konecki","sequence":"additional","affiliation":[{"name":"Division of Clinical Genetics Morgan Stanley Children's Hospital of New York New York New York"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2014,11,26]]},"reference":[{"key":"e_1_2_5_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1096-8628(19991203)87:4<354::AID-AJMG14>3.0.CO;2-Y"},{"issue":"2","key":"e_1_2_5_3_1","first-page":"154","article-title":"Menkes kinky\u2010hair syndrome: Report of a case in a female infant","volume":"33","author":"Barton NW","year":"1983","journal-title":"Neurology"},{"key":"e_1_2_5_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-0004.1994.tb04163.x"},{"key":"e_1_2_5_5_1","doi-asserted-by":"crossref","unstructured":"Favier A Boujet C Joannard .1983. Possibility of a Menkes\u2010like disorder of copper metabolism in a girl. 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