Neuropediatrics 2016; 47 - P07-20
DOI: 10.1055/s-0036-1583695

CANPMR Syndrome and Chromosome 1p32-p31 Deletion Syndrome Coexist in Two Related Individuals Affected by Simultaneous Haplo-insufficiency of CAMTA1 and NIFA Genes

E. G Coci 1, U. Koehler 2, T. Liehr 3, A. Stelzner 1, C. Fink 4, H. Langen 1, J. Riedel 1
  • 1Center of Social Pediatrics and Pediatric Neurology, General Hospital of Celle, Germany;
  • 2Medizinisch Genetisches Zentrum, Munich, Germany
  • 3Institute of Human Genetics, Friedrich Schiller University, Jena University Hospital,Germany;
  • 4Department of Radiology, General Hospital of Celle, Germany

Background: Non-progressive cerebellar ataxia with mental retardation (CANPMR, OMIM 614756) and chromosome 1p32-p31 deletion syndrome (OMIM 613735) are two very rare inherited disorders, which are caused by mono-allelic deficiency (haplo-insufficiency) of calmodulin-binding transcription activator 1 (CAMTA1) and, respectively, nuclear factor 1 A (NFIA) genes. The yet reported patients affected by mono-allelic CAMTA1 dysfunction presented with neonatal hypotonia, delayed and ataxic gait, cerebellar atrophy, psychological delay and speech impairment, while individuals carrying a disrupted NFIA allele suffered from agenesis/hypoplasia of the corpus callosum, ventriculomegaly, developmental delay and urinary tract abnormalities. Both disorders were not seen in one patient together before.

Methods: We used neurological, neuro-radiological, psychological, genetic tests to dissect the so far unique clinical constellation of our 2 patients.

Results: In this study, two related individuals affected by a complex clinical syndrome, characterized by neuro-psychological and nephrological features were characterized for the underlying genetic disorder(s) by molecular cytogenetics. The two individuals presented ataxia, mild tremor, strabismus, dysmorphic facies, macrocephaly, mild mental retardation, hypoplastic corpus callosum and kidney hypoplasia. Genetic investigations revealed a paracentric inversion in the short arm of one chromosome 1 with breakpoints within CAMTA1 and NFIA coding sequences.

Conclusion: To the best of our knowledge, this is the first report of two patients harboring the simultaneous mono-allelic disruptions and consequent haplo-insufficiencies of two genes due to an inversion event. Disruption of CAMTA1 and NFIA genes led to neuro-psychological and nephrological dysfunctions, which comprised clinical features of CANPMR syndrome as well as chromosome 1p32-p31 deletion syndrome.