Cerebro-retinal microangiopathy with calcifications and cysts due to recessive mutations in the CTC1 gene

Rev Neurol (Paris). 2015 May;171(5):445-9. doi: 10.1016/j.neurol.2015.01.566. Epub 2015 Apr 2.


Cerebro-retinal microangiopathy with calcifications and cysts (CRMCC) or Coats plus syndrome is a pleiotropic disorder affecting the eyes, brain, bone and gastrointestinal tract. Its primary pathogenesis involves small vessel obliterative microangiopathy. Recently, autosomal recessively inherited mutations in CTC1 have been reported in CRMCC patients. We herein report an adolescent referred to our hospital following new seizures in a context of an undefined multisystem disorder. Cerebral imaging disclosed asymmetrical leukopathy, intracranial calcifications and cysts. In addition, he presented other typical CRMCC features i.e. a history of intrauterine growth retardation, skeletal demineralization and osteopenia, bilateral exudative vitreo-retinopathy reminiscent of Coats disease, recurrent gastrointestinal hemorrhages secondary to watermelon stomach and variceal bleeding of the esophagus due to idiopathic portal hypertension and telangiectatic and angiodysplasic changes in the small intestine and colon, and anemia due to recurrent bleeding and bone marrow abnormalities. The patient was diagnosed with Coats plus syndrome. CTC1 gene screening confirmed the diagnosis with the identification of heterozygous deleterious mutations. CRMCC due to CTC1 mutations has a broad clinical expressivity. Our case report illustrates the main possible associated phenotypes and their complications, demonstrating the need for a careful etiological search in order to initiate appropriate therapeutic and preventive measures.

Keywords: Bone marrow; Calcifications and cysts; Calcifications et kystes; Hepatoportal sclerosis; Idiopathic portal hypertension; Leuco-encéphalopathie; Leucopathie; Leukoencephalopathy; Maladies des petits vaisseaux; Microangiopathie; Microangiopathy; Small vessels disease; Vitro-rétinopathie.

Publication types

  • Case Reports

MeSH terms

  • Adolescent
  • Ataxia / genetics*
  • Ataxia / physiopathology
  • Brain Neoplasms / genetics*
  • Brain Neoplasms / physiopathology
  • Calcinosis / genetics*
  • Calcinosis / physiopathology
  • Central Nervous System Cysts / genetics*
  • Central Nervous System Cysts / physiopathology
  • Fetal Growth Retardation / genetics
  • Gastrointestinal Hemorrhage / etiology
  • Genes, Recessive / genetics
  • Humans
  • Leukoencephalopathies / genetics*
  • Leukoencephalopathies / physiopathology
  • Magnetic Resonance Imaging
  • Male
  • Muscle Spasticity / genetics*
  • Muscle Spasticity / physiopathology
  • Mutation / genetics
  • Retinal Diseases / genetics*
  • Retinal Diseases / physiopathology
  • Seizures / genetics*
  • Seizures / physiopathology
  • Telomere-Binding Proteins / genetics*


  • Ctc1 protein, human
  • Telomere-Binding Proteins

Supplementary concepts

  • Cerebroretinal Microangiopathy with Calcifications and Cysts