title: Menkes disease with discordant phenotype in female monozygotic twins.
abstract: Menkes disease (MD) is a rare X-linked recessive disorder caused by mutations in the ATP7A gene. This neurodegenerative disorder typically affects males and is characterized by impaired copper distribution and the malfunction of several copper-dependent enzymes. We report clinically discordant female monozygotic twins (MZT) with a heterozygous ATP7A mutation. One twin girl is healthy at the current age of 4 years, whereas the other twin girl developed classical MD, showed disease stabilization under copper histidine treatment but died at the age of 3 years. Presumably, the affected girl developed MD due to skewed X inactivation, although this could not be demonstrated in two tissues (blood, buccal mucosa). This case is a rare example of an affected girl with MD and shows the possibility of a discordant phenotype in MZT girls. As speculated in other X-linked diseases, the process of monozygotic twinning may be associated with skewed X inactivation leading to a discordant phenotype.
authors.affiliation: Genetikum, Genetic Counseling and Diagnostic, Stuttgart and Neu-Ulm, Germany.
authors.forename: Anna Lena
authors.initials: AL
authors.lastname: Burgemeister
authors.affiliation: Genetikum, Genetic Counseling and Diagnostic, Stuttgart and Neu-Ulm, Germany.|Department of Pediatrics and Neuropediatrics, University Medicine, Göttingen, Germany.
authors.forename: Birgit
authors.initials: B
authors.lastname: Zirn
authors.affiliation: Genetikum, Genetic Counseling and Diagnostic, Stuttgart and Neu-Ulm, Germany.
authors.forename: Frank
authors.initials: F
authors.lastname: Oeffner
authors.affiliation: Section on Translational Neuroscience, Molecular Medicine Program, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland.
authors.forename: Stephen G
authors.initials: SG
authors.lastname: Kaler
authors.affiliation: Department of Radiology, SLK-Klinikum, Heilbronn, Germany.
authors.forename: Gunther
authors.initials: G
authors.lastname: Lemm
authors.affiliation: Genetikum, Genetic Counseling and Diagnostic, Stuttgart and Neu-Ulm, Germany.
authors.forename: Eva
authors.initials: E
authors.lastname: Rossier
authors.affiliation: Department of Pediatrics and Neuropediatrics, SLK-Klinikum, Heilbronn, Germany.
authors.forename: Hans-Martin
authors.initials: HM
authors.lastname: Büttel
mesh_terms: D001921:Brain / Q000098:blood supply / Q000473:pathology; D002675:Child, Preschool; D017809:Fatal Outcome; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008279:Magnetic Resonance Imaging; D007706:Menkes Kinky Hair Syndrome / Q000235:genetics / Q000473:pathology*; D010641:Phenotype; D014430:Twins, Monozygotic / Q000235:genetics*
keywords: ATP7A; Menkes disease; discordant phenotype; female monozygotic twins