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Cerebroretinal microangiopathy with calcifications and cysts (CRMCC) or Coats-plus syndrome is a rare multisystem condition in which there is an obliterative angiopathy of small vessels, primarily affecting the brain, eyes, bone and gastrointestinal tract. The most characteristic features of this disorder are retinal telangiectasias and exsudates (Coats disease), distinctive pattern of intracranial calcification with an associated leucodystrophy and brain cysts, skeletal abnormalities, a high risk of gastrointestinal bleeding and portal hypertension. Extraneurological features of Coats-plus differentiate this entity from Labrune syndrome, in which individuals have similar neuroimaging features only. Coats-plus syndrome most frequently occurs due to autosomal recessively inherited variants in CTC1 and STN1 genes, subunits of the CTC1-STN1-TEN1 (CST) complex, responsible for telomere replication, and less frequently implicates the POT1 gene.1–3
We present the case of a girl child referred to the neurology consultation in a context of undefined multisystem disorder. She was born at 38 weeks of gestation with intrauterine growth retardation from healthy non-consanguineous parents. The remaining family history was unremarkable. Early growth and neurological development were normal. There was a history of several fractures after minor trauma episodes, associated with mild osteopenia. At 4 years of age, the patient experienced bilateral loss of vision and the ophthalmological examination revealed retinal vascular anomalies. In the meanwhile, she displayed hyperpigmented reticular lesions on the neck (figure 1A), upper limbs and trunk. In the next year, nail dystrophy (figure 1B) and sparse hypopigmented hair (figure 1C) were notable. She maintained normal growth parameters, along the 50th percentile line for weight and height on the growth chart. She did not refer any neurological complaint, cognitive function was normal, but her neurological examination demonstrated bilateral brisk reflexes in the lower limbs. Initial laboratory workup revealed slight thrombocytopenia and elevation in liver function tests. Liver ultrasound and subsequent biopsy revealed a lobular hepatitis without vascular anomalies. Bone marrow biopsy showed a significant reduction of all haematopoietic series without any pathological and morphological changes.
MRI of the brain revealed a variety of intracranial calcifications, multiple millimetric parenchymal cysts, diffuse hyperintense lesions in cerebral white matter and microhaemorrhages (figure 2). On the basis of all the manifestations demonstrated above, a diagnosis of Coats-plus syndrome was suspected and gene sequencing revealed two heterozygous CTC1 mutations: NM_025099.5 (CTC1): c.391_414del p.Gly131_Asn138del and NM_025099.5 (CTC1): c.2954_2956delGTT p.Cys985del. Both were classified as being probably pathogenic, thus confirming the diagnosis. One year after the diagnosis, the patient maintains no neurological complaints and takes no regular medication.
In conclusion, we report a CRMCC patient with multisystem involvement, with a focus on neuroimaging features, which allowed a directed genetic study that confirmed the diagnosis. A better knowledge of the characteristic findings on neuroimaging of CRMCC may improve our diagnostic ability of this rare entity, preventing unnecessary time-consuming and expensive investigations, and allowing to screen for associated possible complications and to provide genetic counselling.
Coats-plus syndrome is an autosomal recessive genetic disease, with an onset age ranging from infancy to adolescence.
The clinical phenotypes are variable, but neuroimaging findings are remarkable in a context of undefined multisystem disorder: a triad of leucoencephalopathy, intracranial calcifications and parenchymal cysts is strongly suggestive of this diagnosis.
Neuroimaging should be performed when retinal vasculature abnormalities are associated with neurological or syndromic features, even when mild or seemingly unrelated.
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Contributors CM: responsible for conception, scientific research and manuscript writing. MB, FP and JP: responsible for the diagnosis, treatment and follow-up of the patient. FP and JP: reviewers of the article. JP: responsible for reviewing and selecting the images of the patient and reviewers of the article.
Funding This study was funded by Universidade de Coimbra (945074).
Case reports provide a valuable learning resource for the scientific community and can indicate areas of interest for future research. They should not be used in isolation to guide treatment choices or public health policy.
Competing interests None declared.
Provenance and peer review Not commissioned; externally peer reviewed.
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