title: Cerebrotendinous xanthomatosis (CTX): an association of pulverulent cataracts and pseudo-dominant developmental delay in a family with a splice site mutation in CYP27A1--a case report.
abstract: OBJECTIVE
  A 15-year-old boy with developmental delay presented to the pediatric ophthalmology clinic with bilateral pulverulent cataracts. The family was examined for developmental delay, cataracts and systemic problems.
  
  
  METHODS
  The parents were consanguineous and originally from Bangladesh. All the children were born in the UK. The mother and 5 children had developmental delay. Three children had global developmental delay, diarrhea and pulverulent cataracts. Two children had microcephaly, developmental delay, constipation and no cataracts. The mother did not have microcephaly, cataracts or gastrointestinal problems. Linkage analysis via autozygosity testing was performed for detection of loci and candidate genes. The patients with cataracts were segregated with homozygous mutations in the CYP27A1 (G to A substitution at position +1 of intron 6).
  
  
  RESULTS
  The complex nature of this family's findings suggested that it had an unusual autosomal dominant condition with variable expression. Autozygosity testing demonstrated that three members had Cerebrotendinous xanthomatosis (CTX), which is inherited in an autosomal recessive manner. The aetiology of the developmental delay in other family members remains unknown.
  
  
  CONCLUSIONS
  Cerebrotendinous xanthomatosis is a rare autosomal recessive condition that can result in neurological deficits and early death if left untreated. In view of the reversible nature of the condition with appropriate treatment, there needs to be a high level of suspicion of CTX for any child with cataracts and developmental delay even if the pattern of inheritance is not straightforward at initial assessment.
authors.affiliation: Department of Ophthalmology, Barts and the London NHS Trust, London, UK. rbourkiza@doctors.org.uk
authors.forename: Rabia
authors.initials: R
authors.lastname: Bourkiza
authors.forename: Sarah
authors.initials: S
authors.lastname: Joyce
authors.forename: Himanshu
authors.initials: H
authors.lastname: Patel
authors.forename: Michelle
authors.initials: M
authors.lastname: Chan
authors.forename: Esther
authors.initials: E
authors.lastname: Meyer
authors.forename: Eamonn R
authors.initials: ER
authors.lastname: Maher
authors.forename: M Ashwin
authors.initials: MA
authors.lastname: Reddy
mesh_terms: D000293:Adolescent; D002386:Cataract / Q000175:diagnosis / Q000235:genetics*; D053493:Cholestanetriol 26-Monooxygenase / Q000235:genetics*; D003241:Consanguinity; D004252:DNA Mutational Analysis; D002658:Developmental Disabilities / Q000175:diagnosis / Q000235:genetics*; D007839:Functional Laterality; D005808:Genes, Recessive; D008040:Genetic Linkage; D018095:Germ-Line Mutation; D006801:Humans; D008297:Male; D018895:Microsatellite Repeats; D020125:Mutation, Missense / Q000235:genetics*; D010375:Pedigree; D022821:RNA Splice Sites / Q000235:genetics*; D019294:Xanthomatosis, Cerebrotendinous / Q000175:diagnosis / Q000235:genetics*
chemical_list: D022821:RNA Splice Sites; C506831:CYP27A1 protein, human; D053493:Cholestanetriol 26-Monooxygenase