title: Harlequin ichthyosis: a review of clinical and molecular findings in 45 cases.
abstract: OBJECTIVE
  To assess the clinical outcomes of 45 cases of harlequin ichthyosis and review the underlying ABCA12 gene mutations in these patients.
  
  
  METHODS
  Multicenter, retrospective, questionnaire-based survey.
  
  
  METHODS
  Dermatology research institute.
  
  
  METHODS
  Patients with harlequin ichthyosis for whom we had performed ABCA12 mutation analysis.
  
  
  METHODS
  Referring physicians were asked to complete a questionnaire using the patients' notes, detailing the clinical outcome of the affected child. In each case, the causative ABCA12 mutation was identified using standard polymerase chain reaction and sequencing techniques.
  
  
  RESULTS
  Of the 45 cases, the ages of the survivors ranged from 10 months to 25 years, with an overall survival rate of 56%. Death usually occurred in the first 3 months and was attributed to sepsis and/or respiratory failure in 75% of cases. The early introduction of oral retinoids may improve survival, since 83% of those treated survived, whereas 76% who were not given retinoids died. Recurrent skin infections in infancy affected one-third of patients. Problems maintaining weight affected 44%. Three children developed an inflammatory arthritis, and developmental delay was reported in 32%. Mutation analysis revealed that 52% of survivors had compound heterozygous mutations, whereas all deaths were associated with homozygous mutations.
  
  
  CONCLUSIONS
  Harlequin ichthyosis should be regarded as a severe chronic disease that is not invariably fatal. With improved neonatal care and probably the early introduction of oral retinoids, the number of survivors is increasing. Compound heterozygotes appear to have a survival advantage.
authors.affiliation: Centre for Cutaneous Research, Blizard Institute of Cell and Molecular Science, Barts and the London School of Medicine and Dentistry, Queen Mary, University of London, 4 Newark St, London E1 2AT, England. s.rajpopat@qmul.ac.uk
authors.forename: Shefali
authors.initials: S
authors.lastname: Rajpopat
authors.forename: Celia
authors.initials: C
authors.lastname: Moss
authors.forename: Jemima
authors.initials: J
authors.lastname: Mellerio
authors.forename: Anders
authors.initials: A
authors.lastname: Vahlquist
authors.forename: Agneta
authors.initials: A
authors.lastname: Gånemo
authors.forename: Maritta
authors.initials: M
authors.lastname: Hellstrom-Pigg
authors.forename: Andrew
authors.initials: A
authors.lastname: Ilchyshyn
authors.forename: Nigel
authors.initials: N
authors.lastname: Burrows
authors.forename: Giles
authors.initials: G
authors.lastname: Lestringant
authors.forename: Aileen
authors.initials: A
authors.lastname: Taylor
authors.forename: Cameron
authors.initials: C
authors.lastname: Kennedy
authors.forename: David
authors.initials: D
authors.lastname: Paige
authors.forename: John
authors.initials: J
authors.lastname: Harper
authors.forename: Mary
authors.initials: M
authors.lastname: Glover
authors.forename: Philip
authors.initials: P
authors.lastname: Fleckman
authors.forename: David
authors.initials: D
authors.lastname: Everman
authors.forename: Mohamad
authors.initials: M
authors.lastname: Fouani
authors.forename: Hulya
authors.initials: H
authors.lastname: Kayserili
authors.forename: Diana
authors.initials: D
authors.lastname: Purvis
authors.forename: Emma
authors.initials: E
authors.lastname: Hobson
authors.forename: Carol
authors.initials: C
authors.lastname: Chu
authors.forename: Charles
authors.initials: C
authors.lastname: Mein
authors.forename: David
authors.initials: D
authors.lastname: Kelsell
authors.forename: Edel
authors.initials: E
authors.lastname: O'Toole
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000235:genetics*; D000293:Adolescent; D000328:Adult; D001168:Arthritis / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D002908:Chronic Disease; D005183:Failure to Thrive / Q000209:etiology; D005260:Female; D006801:Humans; D017490:Ichthyosis, Lamellar / Q000150:complications / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality*; D007223:Infant; D008297:Male; D009154:Mutation; D011379:Prognosis; D012131:Respiratory Insufficiency / Q000209:etiology; D012176:Retinoids / Q000627:therapeutic use; D012189:Retrospective Studies; D018805:Sepsis / Q000209:etiology / Q000401:mortality; D012874:Skin Diseases, Infectious / Q000209:etiology / Q000401:mortality; D055815:Young Adult
chemical_list: C473801:ABCA12 protein, human; D018528:ATP-Binding Cassette Transporters; D012176:Retinoids