TECPR2 mutations cause a new subtype of familial dysautonomia like hereditary sensory autonomic neuropathy with intellectual disability

Eur J Paediatr Neurol. 2016 Jan;20(1):69-79. doi: 10.1016/j.ejpn.2015.10.003. Epub 2015 Oct 22.


Background: TECPR2 was first described as a disease causing gene when the c.3416delT frameshift mutation was found in five Jewish Bukharian patients with similar features. It was suggested to constitute a new subtype of complex hereditary spastic paraparesis (SPG49).

Results: We report here 3 additional patients from unrelated non-Bukharian families, harboring two novel mutations (c.1319delT, c.C566T) in this gene. Accumulating clinical data clarifies that in addition to intellectual disability and evolving spasticity the main disabling feature of this unique disorder is autonomic-sensory neuropathy accompanied by chronic respiratory disease and paroxysmal autonomic events.

Conclusion: We suggest that the disease should therefore be classified as a new subtype of hereditary sensory-autonomic neuropathy. The discovery of additional mutations in non-Bukharian patients implies that this disease might be more common than previously appreciated and should therefore be considered in undiagnosed cases of intellectual disability with autonomic features and respiratory symptoms regardless of demographic origin.

Keywords: Autophagy; HSAN III; Hereditary spastic paraparesis; IKBKAP; Jewish Ashkenazi; TECPR2.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carrier Proteins / chemistry
  • Carrier Proteins / genetics*
  • Child, Preschool
  • Computational Biology
  • DNA / genetics
  • Dysautonomia, Familial / genetics*
  • Electrodiagnosis
  • Exome
  • Frameshift Mutation / genetics
  • Hereditary Sensory and Autonomic Neuropathies / genetics*
  • Hereditary Sensory and Autonomic Neuropathies / psychology
  • Humans
  • Infant
  • Infant, Newborn
  • Intellectual Disability / genetics*
  • Intellectual Disability / psychology
  • Jews
  • Male
  • Models, Molecular
  • Nerve Tissue Proteins / chemistry
  • Nerve Tissue Proteins / genetics*
  • Neurologic Examination
  • Pedigree
  • Respiration Disorders / etiology
  • Respiration Disorders / genetics
  • Spastic Paraplegia, Hereditary / genetics*
  • Spastic Paraplegia, Hereditary / psychology


  • Carrier Proteins
  • Nerve Tissue Proteins
  • TECPR2 protein, human
  • DNA