General description

Cerebroretinal microangiopathy with calcifications and cysts (CRMCC), also known as Coats plus syndrome, is a rare autosomal recessive genetic disorder that represents a multisystem disease with variable clinical phenotypes. The primary pathogenesis involves a small vessel obliterative microangiopathy affecting multiple organ systems, particularly the brain, eyes, bone, and gastrointestinal tract.

The molecular basis of CRMCC has been linked to mutations in genes involved in telomere maintenance, particularly the CTC1-STN1-TEN1 (CST) complex. Mutations in the CTC1 gene (conserved telomere maintenance component 1) are the most commonly identified genetic cause, with biallelic mutations resulting in compound heterozygous states. The CST complex plays essential roles in telomere replication and maintenance of telomeric structural integrity, and disruption of this complex leads to defective telomere maintenance.

The obliterative microangiopathy characteristic of CRMCC results in angiomatous-like rearrangements of the microvessels, together with degenerative secondary changes of other cellular elements. This constitutional, diffuse cerebral microangiopathy leads to progressive microcystic, then macrocystic, parenchymal degeneration.

Clinical manifestations

CRMCC presents with a broad spectrum of clinical manifestations that typically emerge from infancy to adolescence, with considerable phenotypic variability.

The neurological symptoms vary depending on the site of brain abnormalities and commonly include partial epilepsy, asymmetric spasticity, ataxia, and cognitive impairment. The cognitive impairment particularly affects visuospatial and visuoconstructive skills initially.

Ophthalmological manifestations are characteristic and include bilateral retinal telangiectasia and exudates reminiscent of Coats disease. Patients may present with leukokoria, redness, irritation, and impaired vision resulting from retinal detachment and glaucoma. Some patients may experience bilateral loss of vision.

Systemic manifestations are common and include intrauterine growth retardation, preterm birth, skeletal demineralization and osteopenia leading to increased fracture risk. Gastrointestinal complications include recurrent bleeding secondary to watermelon stomach, variceal bleeding of the esophagus due to idiopathic portal hypertension, and telangiectatic and angiodysplastic changes in the small intestine and colon. Hematological abnormalities include anemia due to recurrent bleeding and bone marrow abnormalities, along with thrombocytopenia.

References

1. Xu, Wenrui, et al. "Cerebroretinal microangiopathy with calcifications and cysts: A case report." Medicine 96.1 (2017): e5545.