title: Cerebro-retinal microangiopathy with calcifications and cysts due to recessive mutations in the CTC1 gene.
abstract: 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.
authors.affiliation: Université Paris-Sud, 63, rue Gabriel-Péri, 94276 Le Kremlin-Bicêtre cedex, France; Department of pediatrics, CHU de Bicêtre, 78, rue du Général-Leclerc, 94275 Le Kremlin-Bicêtre cedex, France.
authors.forename: A
authors.initials: A
authors.lastname: Bisserbe
authors.affiliation: Department of hematology, CHU de Bicêtre, 78, rue du Général-Leclerc, 94275 Le Kremlin-Bicêtre cedex, France.
authors.forename: G
authors.initials: G
authors.lastname: Tertian
authors.affiliation: Université Paris-Sud, 63, rue Gabriel-Péri, 94276 Le Kremlin-Bicêtre cedex, France; Department of gastroenterology, CHU de Bicêtre, 78, rue du Général-Leclerc, 94275 Le Kremlin-Bicêtre cedex, France.
authors.forename: C
authors.initials: C
authors.lastname: Buffet
authors.affiliation: Université Paris-Sud, 63, rue Gabriel-Péri, 94276 Le Kremlin-Bicêtre cedex, France; Department of hematology, CHU de Bicêtre, 78, rue du Général-Leclerc, 94275 Le Kremlin-Bicêtre cedex, France.
authors.forename: A
authors.initials: A
authors.lastname: Turhan
authors.affiliation: Université Paris-Sud, 63, rue Gabriel-Péri, 94276 Le Kremlin-Bicêtre cedex, France; Department of internal medicine, CHU de Bicêtre, 78, rue du Général-Leclerc, 94275 Le Kremlin-Bicêtre cedex, France.
authors.forename: O
authors.initials: O
authors.lastname: Lambotte
authors.affiliation: Department of radiology, CHU de Bicêtre, 78, rue du Général-Leclerc, 94275 Le Kremlin-Bicêtre cedex, France; Department of neurology, CHU de Bicêtre, 78, rue du Général-Leclerc, 94275 Le Kremlin-Bicêtre cedex, France.
authors.forename: G
authors.initials: G
authors.lastname: Nasser
authors.affiliation: Department of pediatrics, CHU de Bicêtre, 78, rue du Général-Leclerc, 94275 Le Kremlin-Bicêtre cedex, France.
authors.forename: P
authors.initials: P
authors.lastname: Alvin
authors.affiliation: Université Paris-Sud, 63, rue Gabriel-Péri, 94276 Le Kremlin-Bicêtre cedex, France; Department of pediatrics, CHU de Bicêtre, 78, rue du Général-Leclerc, 94275 Le Kremlin-Bicêtre cedex, France.
authors.forename: M
authors.initials: M
authors.lastname: Tardieu
authors.affiliation: Service de génétique, hôpital Lariboisière, 2, rue Ambroise-Paré, 75010 Paris, France; Inserm UMR-S 1161 Paris Diderot university, site Villemin, 10, avenue de Verdun, 75010 Paris, France.
authors.forename: F
authors.initials: F
authors.lastname: Riant
authors.affiliation: Inserm UMR-S 1161 Paris Diderot university, site Villemin, 10, avenue de Verdun, 75010 Paris, France.
authors.forename: F
authors.initials: F
authors.lastname: Bergametti
authors.affiliation: Service de génétique, hôpital Lariboisière, 2, rue Ambroise-Paré, 75010 Paris, France; Inserm UMR-S 1161 Paris Diderot university, site Villemin, 10, avenue de Verdun, 75010 Paris, France.
authors.forename: E
authors.initials: E
authors.lastname: Tournier-Lasserve
authors.affiliation: Université Paris-Sud, 63, rue Gabriel-Péri, 94276 Le Kremlin-Bicêtre cedex, France; Department of neurology, CHU de Bicêtre, 78, rue du Général-Leclerc, 94275 Le Kremlin-Bicêtre cedex, France. Electronic address: christian.denier@bct.aphp.fr.
authors.forename: C
authors.initials: C
authors.lastname: Denier
mesh_terms: D000293:Adolescent; D001259:Ataxia / Q000235:genetics* / Q000503:physiopathology; D001932:Brain Neoplasms / Q000235:genetics* / Q000503:physiopathology; D002114:Calcinosis / Q000235:genetics* / Q000503:physiopathology; D020863:Central Nervous System Cysts / Q000235:genetics* / Q000503:physiopathology; D005317:Fetal Growth Retardation / Q000235:genetics; D006471:Gastrointestinal Hemorrhage / Q000209:etiology; D005808:Genes, Recessive / Q000235:genetics; D006801:Humans; D056784:Leukoencephalopathies / Q000235:genetics* / Q000503:physiopathology; D008279:Magnetic Resonance Imaging; D008297:Male; D009128:Muscle Spasticity / Q000235:genetics* / Q000503:physiopathology; D009154:Mutation / Q000235:genetics; D012164:Retinal Diseases / Q000235:genetics* / Q000503:physiopathology; D012640:Seizures / Q000235:genetics* / Q000503:physiopathology; D034501:Telomere-Binding Proteins / Q000235:genetics*
chemical_list: C544945:Ctc1 protein, human; D034501:Telomere-Binding Proteins
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