Clinical variability of CMS-EA (congenital myasthenic syndrome with episodic apnea) due to identical CHAT mutations in two infants (2005)

Author(s): Barisic N, Muller JS, Paucic-Kirincic E, Gazdik M, Lah-Tomulic K, Pertl A, Sertic J, Zurak N, Lochmuller H, Abicht A

    Abstract: Congenital myasthenic syndromes (CMS) result from mutations in various synapse-associated genes. Mutations in the choline acetyltransferase (CHAT) gene cause a presynaptic CMS associated with episodic apnea (CMS-EA). We present two unrelated Croatian children affected by CMS-EA. Beside other clinical findings characteristic for CMS, both patients manifested intermittent apneas since early infancy. Whereas the course of disease is mild in the female patient (patient 2), the male patient (patient 1) experienced recurrent and severe episodes of apnea despite adequate treatment with AChE-inhibitors and shows a global developmental delay with delayed myelination and signs of hypoxic-ischemic injury in brain imaging. Interestingly, sequencing of the CHAT gene revealed identical, compound heterozygous mutations S694C and T354M in both children. These findings are in line with a remarkable clinical heterogeneity observed in patients with CHAT mutations and emphasize the potential role of apneic crises for the development of secondary hypoxic brain damage and psychomotor retardation.

      • Date: 13-12-2004
      • Journal: European Journal of Paediatric Neurology
      • Volume: 9
      • Issue: 1
      • Pages: 7-12
      • Publisher: Elsevier Ltd
      • Publication type: Article
      • Bibliographic status: Published

      Keywords: Apnea/complications/ genetics Choline O-Acetyltransferase/ genetics Croatia Developmental Disabilities/etiology Female Humans Hypoxia, Brain/etiology Infant, Newborn Male Mutation, Missense/ genetics Myasthenic Syndromes, Congenital/complications/ genetics Phenotype Respiratory Insufficiency/etiology


      Professor Hanns Lochmuller
      Professor of Experimental Myology