Infantile hypotonia as a presentation of Rett syndrome

Am J Med Genet. 2002 Aug 15;111(3):238-42. doi: 10.1002/ajmg.10633.


Rett syndrome (RTT) is classically defined by meeting certain clinical diagnostic criteria. It affects mostly females, and one possible pathogenic mechanism was considered to involve mitochondrial function. This was based on the finding of ultrastructural alterations in the mitochondria and decreased respiratory chain enzyme activity. However, the principal etiology of RTT has since been found to be mutations in the MECP2 gene, which is located on the X chromosome. Molecular analysis has allowed the phenotype of MECP2 mutations to be broadened beyond RTT to include girls who have mild mental retardation, autism, and an Angelman syndrome phenotype, as well as males with severe encephalopathy. We present a girl with a previously described mutation in the MECP2 gene whose phenotype is of atypical RTT. She presented with hypotonia and developmental delay in infancy without a clear period of normal development. As part of her evaluation for hypotonia, a muscle biopsy and respiratory chain enzyme analysis showed a slight decrease in respiratory chain enzyme activity consistent with previous reports. This report supports broadening the phenotype of patients who should be considered for MECP2 mutation analysis to include cases of developmental delay and hypotonia without evidence of an initial period of normal development. Furthermore, it supports the hypothesis of an underlying secondary defect in energy metabolism contributing to the pathogenesis of RTT.

Publication types

  • Case Reports

MeSH terms

  • Amino Acid Substitution
  • Child, Preschool
  • Chromosomal Proteins, Non-Histone*
  • DNA-Binding Proteins / genetics
  • Electron Transport / genetics
  • Electron Transport / physiology
  • Female
  • Humans
  • Infant
  • Methyl-CpG-Binding Protein 2
  • Mitochondrial Diseases / genetics
  • Mitochondrial Diseases / physiopathology
  • Muscle Hypotonia / etiology
  • Muscle Hypotonia / genetics*
  • Repressor Proteins*
  • Rett Syndrome / etiology
  • Rett Syndrome / genetics
  • Rett Syndrome / physiopathology*


  • Chromosomal Proteins, Non-Histone
  • DNA-Binding Proteins
  • MECP2 protein, human
  • Methyl-CpG-Binding Protein 2
  • Repressor Proteins