title: Dropped head congenital muscular dystrophy caused by de novo mutations in LMNA.
abstract: BACKGROUND
  Dropped head syndrome is an easily recognizable clinical presentation of Lamin A/C-related congenital muscular dystrophy. Patients usually present in the first year of life with profound neck muscle weakness, dropped head, and elevated serum creatine kinase.
  
  
  METHODS
  Two patients exhibited head drop during infancy although they were able to sit independently. Later they developed progressive axial and limb-girdle weakness. Creatine kinase levels were elevated and muscle biopsies of both patients showed severe dystrophic changes. The distinctive clinical hallmark of the dropped head led us to the diagnosis of Lamin A/C-related congenital muscular dystrophy, with a pathogenic de novo mutation p.Glu31del in the head domain of the Lamin A/C gene in both patients. Remarkably, one patient also had a central involvement with white matter changes on brain magnetic resonance imaging.
  
  
  CONCLUSIONS
  Lamin A/C-related dropped-head syndrome is a rapidly progressive congenital muscular dystrophy and may lead to loss of ambulation, respiratory insufficiency, and cardiac complications. Thus, the genetic diagnosis of dropped-head syndrome as L-CMD and the implicated clinical care protocols are of vital importance for these patients. This disease may be underdiagnosed, as only a few genetically confirmed cases have been reported.
authors.affiliation: Dokuz Eylül University, School of Medicine, Department of Pediatrics, Division of Child Neurology, 35340 İzmir, Turkey.
authors.forename: Pakize
authors.initials: P
authors.lastname: Karaoglu
authors.affiliation: Children's National Medical Center, Research Center for Genetic Medicine, 20010 Washington DC, USA.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Quizon
authors.affiliation: University Children's Hospital Cologne, 50931 Cologne, Germany; Center for Molecular Medicine, 50931 Cologne, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Pergande
authors.affiliation: University Children's Hospital Cologne, 50931 Cologne, Germany; Center for Molecular Medicine, 50931 Cologne, Germany.
authors.forename: Haicui
authors.initials: H
authors.lastname: Wang
authors.affiliation: Dokuz Eylül University, School of Medicine, Department of Pediatrics, Division of Child Neurology, 35340 İzmir, Turkey.
authors.forename: Ayşe Ipek
authors.initials: AI
authors.lastname: Polat
authors.affiliation: Dokuz Eylül University, School of Medicine, Department of Pathology, 35340 İzmir, Turkey.
authors.forename: Ayca
authors.initials: A
authors.lastname: Ersen
authors.affiliation: Dokuz Eylül University, School of Medicine, Department of Pathology, 35340 İzmir, Turkey.
authors.forename: Erdener
authors.initials: E
authors.lastname: Özer
authors.affiliation: Center for Molecular Medicine, 50931 Cologne, Germany.
authors.forename: Lena
authors.initials: L
authors.lastname: Willkomm
authors.affiliation: Dokuz Eylül University, School of Medicine, Department of Pediatrics, Division of Child Neurology, 35340 İzmir, Turkey.
authors.forename: Semra
authors.initials: S
authors.lastname: Hiz Kurul
authors.affiliation: Children's National Medical Center, Research Center for Genetic Medicine, 20010 Washington DC, USA.
authors.forename: Raúl
authors.initials: R
authors.lastname: Heredia
authors.affiliation: Dokuz Eylül University, School of Medicine, Department of Pediatrics, Division of Child Neurology, 35340 İzmir, Turkey.
authors.forename: Uluç
authors.initials: U
authors.lastname: Yis
authors.affiliation: Mayo Clinic, Department of Neurology, Rochester, MN, USA.
authors.forename: Duygu
authors.initials: D
authors.lastname: Selcen
authors.affiliation: Children's National Medical Center, Research Center for Genetic Medicine, 20010 Washington DC, USA; University Children's Hospital Cologne, 50931 Cologne, Germany; Center for Molecular Medicine, 50931 Cologne, Germany. Electronic address: sebahattin.cirak@uk-koeln.de.
authors.forename: Sebahattin
authors.initials: S
authors.lastname: Çirak
mesh_terms: D001921:Brain / Q000000981:diagnostic imaging; D002675:Child, Preschool; D003937:Diagnosis, Differential; D006257:Head / Q000503:physiopathology; D006801:Humans; D007223:Infant; D034904:Lamin Type A / Q000235:genetics*; D008297:Male; D009132:Muscles / Q000473:pathology; D009136:Muscular Dystrophies / Q000175:diagnosis* / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D009154:Mutation; D011187:Posture; D066127:White Matter / Q000000981:diagnostic imaging
chemical_list: C494847:LMNA protein, human; D034904:Lamin Type A
keywords: Dropped head; LMNA-related congenital muscular dystrophy; Lamin A/C gene; White matter