Here, we describe eight previously unreported cases, and present an update on one of the original Coats plus patients to highlight the emerging core clinical features of the "cerebroretinal microangiopathy with calcification and cysts" (CRMCC) phenotype [ncbi.nlm.nih.gov]

Observations: A 15-year-old girl with a history of small for gestational age, short stature, microcephaly, thinning/ greying of scalp hair, skin hyperpigmentation, nail ridging, and multiple pathological fractures presented with bilateral Coats-like retinopathy [jdc.jefferson.edu]

Only 28 cases were detailed concerning the precise clinical presentation in the literature. [clinicaltrials.gov]

Here, we present the investigation of a fourth child who presented to us with retinal exudates, intracranial calcifications and developmental delay, in keeping with a diagnosis of CP, and later went on to develop pancytopenia and gastrointestinal bleeding [repository.cam.ac.uk]

• Anemia

  Response to the article by Linnankivi et al., entitled ‘Cerebroretinal microangiopathy with calcifications and cyst, Revesz syndrome and aplastic anemia’. [nature.com]

  Conclusion: Multiple characteristics (progeroid appearance, cerebral calcifications of the basal ganglia, osteopenia, bone anomalies, fractures, growth failure, anemia) are consistent with of Coats plus syndrome, but this patient is the first to present [abstracts.eurospe.org]

  complementation group A fanconi anaemia complementation group A gene fanconi anaemia, complementation group A fanconi anemia complementation group A gene FANCA FA-H FAA FACA FAH FANCH 607139 3582 fanconi anemia, complementation group B fanconi anaemia [ukgtn.nhs.uk]

  Spinal tap and blood test results are typically normal but may find anemia and thrombocytopenia in some children. Is There a Treatment for CRMCC? There is no treatment that can cure CRMCC and treatment is symptomatic. [huntershope.org]

  1 autosomal dominant dyskeratosis congenita and aplastic anemia Vulliamy et al, 2004 Parry et al, 2011 r.176a>c P3 aplastic anemia Vulliamy et al, 2011 r.178g>a P3 aplastic anemia Marrone et al, 2007.1 r.180c>u P3 aplastic anemia Marrone et al, 2007.1 [telomerase.asu.edu]

• Short Stature

  Observations: A 15-year-old girl with a history of small for gestational age, short stature, microcephaly, thinning/ greying of scalp hair, skin hyperpigmentation, nail ridging, and multiple pathological fractures presented with bilateral Coats-like retinopathy [jdc.jefferson.edu]

  We conclude that the CRMCC-associated bone disease is characterized by low BMD and pathological fractures with delayed healing, metaphyseal changes, and short stature pre- and postnatally. LRP5 is not a disease-causing gene in CRMCC. [ncbi.nlm.nih.gov]

  stature, and intellectual disabilities) 759.89 Rud's (mental deficiency, epilepsy, and infantilism) 759.89 Russell (-Silver) (congenital hemihypertrophy and short stature) 759.89 Seckel's 759.89 sick Silver's (congenital hemihypertrophy and short stature [icd9data.com]

  We conclude that the CRMCC‐associated bone disease is characterized by low BMD and pathological fractures with delayed healing, metaphyseal changes, and short stature pre‐ and postnatally. [doi.org]

  This case also illustrates the importance of WES in the diagnosis of children with extreme short stature. [abstracts.eurospe.org]

• Asymptomatic

  Their cerebral lesions often are asymptomatic when the child presents to the ophthalmologist with strabismus, leukokoria, or glaucoma from exudative retinopathy [5,6]. [karger.com]

  It could be assumed that in the presence of extra central exudation, the patient would have remained visually asymptomatic. [humangeneticsjournal.com]

  The first symptom or sign was decreased visual acuity in 68 cases (34%), strabismus in 37 (23%), leukocoria in 31 (20%), and 13 patients (8%) were asymptomatic. Visual acuity at presentation was 20/200 to no light perception in 121 eyes (76%). [eyewiki.aao.org]

• Pathologist

  Coats commenced work at the Royal London Ophthalmic Hospital in 1902, became a FRCS in 1903 and in 1905 he was appointed curator and pathologist at Moorfields hospital. [whonamedit.com]

  He was subsequently appointed pathologist and curator at Moorfields in 1905 and assistant ophthalmic surgeon at the Great Northern Central Hospital a year later. [karger.com]

  Adult-onset leukoencephalopathies with increased cerebral volume can present a potentially challenging diagnosis for the pathologist. [pubfacts.com]

• Severe Pain

  In two thirds of patients who underwent complete resection, local recurrences were the first site of relapse. [18] This distribution of relapses was noted in several studies reviewed by Detterbeck. [emedicine.medscape.com]

• Strabismus

  Strabismus. 2005 Dec;13(4):201-4. 35. Schielke KC, Hilton AJ, Brown R. Acquired Brown’s syndrome associated with preseptal cellulitis. Strabismus. 2008 Jul-Sep;16(3):95-6. 36. Pandey PK, Chaudhuri Z, Bhatia A. [neuroophthalmology.ca]

  Brodsky, Cerebroretinal microangiopathy with calcifications and cysts (CRMCC) or “Coats Plus”: when peripheral retinal vasculature signals neurologic disease, Journal of American Association for Pediatric Ophthalmology and Strabismus, 21, 5, (420), (2017 [doi.org]

  Hoyt and Taylor, Pediatric Ophthalmology and Strabismus, fourth edition, Eslevier, 2012. References ↑ Coats G. Forms of retinal diseases with massive exudation. [eyewiki.aao.org]

  J Pediatr Ophthalmol Strabismus 2006;43:313-315. 11. Shields JA, Shields CL, Honavar SG, Demirci H, Cater J. Classification and management of Coats disease: The 2000 Proctor Lecture. Am J Ophthalmol 2001;131:572-583. 12. [reviewofophthalmology.com]

  Hyperplasia of iris Narrow palpebral fissures (the opening between upper and lower eyelids) High myopia Strabismus Cataracts Grey spots on the iris Duane’s Syndrome A congenital rare type of strabismus. [tsbvi.edu]

• Photophobia

  The clinical signs of congenital glaucoma can be present during the first week of life photophobia ; clear watery eyes ; megalocornea, corresponding to an increased corneal diameter, due to increased intraocular pressure: the eye of the newborn deforms [sites.uclouvain.be]

  Total or partial absence of the iris Cataracts Ptosis Decreased visual acuity Photophobia Nystagmus Wilson's Disease This is a recessive inheritance pattern, which includes neurological symptoms, cirrhosis of the liver, and faulty renal function. [tsbvi.edu]

• Sparse Hair

  In the latter, a progressive formation of parenchymal brain cysts is a special feature, whereas Coats plus is characterized by intrauterine growth retardation, bilateral retinal telangiectasias and exudations (Coats disease), sparse hair, and dysplastic [ncbi.nlm.nih.gov]

  AB - In 1988 we reported two sisters with bilateral Coats' disease, sparse hair, dystrophic nails, and primeval splashes of intracranial calcification. [research.manchester.ac.uk]

  hair, dystrophic nails, and primeval splashes of intracranial calcification. [archive-ouverte.unige.ch]

  Abstract We describe two sisters who have bilateral Coats reaction of the retina, intracranial calcification, sparse hair and dysplastic nails. The younger sibling has in addition distinct retinal angiomas in one eye. [doi.org]

• Flushing

  The effect is extremely pronounced because the other half of the face compensates by sweating and flushing excessively — a condition called hyperhidrosis. [scienceline.org]

  In her diary, Ms Russell said: “His face was flushed and he was very hot to touch and he had wax leaking from his ear. [telegraph.co.uk]

  It also helps relieve tension headaches and flush excess lactic acid from muscle tissue into the bloodstream and out of the body—because it’s not just strenuous exercise that causes the release of lactic acid; stress does, too. [goop.com]

• Thin Skin

  At 23 yrs she presented with a height of 117.7 cm (-7.0 SDS), progeroid appearance, elevated upper/lower segment ratio (1.2), BMI -2.3 SDS, head circumference -2.0 SDS, breast stage 2, thin skin and hair, microdontia/oligodontia, high palate, right thumb [abstracts.eurospe.org]

• Cerebral Calcification

  Extensive cerebral calcifications and leukoencephalopathy have been reported in two rare disorders Coats plus and leukoencephalopathy with calcifications and cysts. [ncbi.nlm.nih.gov]

  Coats' Plus: A Progressive Familial Syndrome of Bilateral Coats' Disease, Characteristic Cerebral Calcification, Leukoencephalopathy, Slow Pre- and Post-Natal Linear Growth and Defects of Bone Marrow and Integument. [research.manchester.ac.uk]

  Corboy, Adult Cases of Leukoencephalopathy, Cerebral Calcifications, and Cysts: Expanding the Spectrum of the Disorder, Journal of Neuropathology & Experimental Neurology, 68, 4, (432), (2009). [doi.org]

  Leukoencephalopathy, cerebral calcifications and cysts: new observations. Neurology 2004;62:1206-1209. [ Links ] 3. Sener U, Zorlu Y, Men S, Bayol U, Zanapalioglu U. Leukoencephalopathy, cerebral calcifications, and cysts. [scielo.br]

  At the age of 37 years, cerebral calcifications were detected, but she exhibited no cognitive or motor problems. [pubfacts.com]

Despite numerous workups, no specific etiology was identified for the GI bleeding. Conclusion: Previous reports have not investigated cause of GI bleeding, since it is extremely rare in the literature. [miami.pure.elsevier.com]

A referral to a geneticist led to further genetic workup using wholegenome sequencing, which detected two recessively inherited compound heterozygous variants, NR_033294.1 n.*9C>T and n.24C>T, in the nonprotein coding gene SNORD118, diagnostic of LCC. [e-jmd.org]

These patients are often family members of a patient with advanced disease, who are identified during the screening workup for suspected FEVR. [reviewofophthalmology.com]

Extensive workup of the patient was undertaken. It included a muscle biopsy for suspected mitochondrial disorder. [academic.oup.com]

• Thrombocytopenia

  […] test, please contact CGC Genetics 2 Maximum shipping time to ensure sample quality Turnaround Time (Days) - 60 CPT Codes - 81479 Specialties - Rare diseases, Neurology / Neuropediatrics, Ophthalmology, Pediatrics CGC Reference - 2043 Associated Tests Thrombocytopenia [cgcgenetics.com]

  Spinal tap and blood test results are typically normal but may find anemia and thrombocytopenia in some children. Is There a Treatment for CRMCC? There is no treatment that can cure CRMCC and treatment is symptomatic. [huntershope.org]

  He was referred to our clinic due to thrombocytopenia and macrocytosis. Physical examination revealed decreased visual acuity, hyperpigmented reticular lesions on the neck, upper limbs and trunk, leukoplakia, and nail dystrophy (figure 1). [casereports.bmj.com]

  Additional findings in some individuals are portal hypertension and liver failure.[1][2] Blood[edit] Many affected children develop anemia, which may be macrocytic in type.[1][2][4] Some also develop thrombocytopenia. [en.wikipedia.org]

  Some patients also show hair, skin, and nail changes, as well as anemia and thrombocytopenia. Intrauterine growth retardation has been reported. Molecular genetics The disorder can be caused by biallelic mutations in the CTC1, SNORD118 or POT1 gene. [bredagenetics.com]

We characterized the patients' phenotype, recapitulated it in a zebrafish model and rescued cellular and clinical aspects by the ectopic expression of wild-type STN1 or by thalidomide treatment. [mdanderson.elsevierpure.com]

Is There a Treatment for CRMCC? There is no treatment that can cure CRMCC and treatment is symptomatic. Helpful Resources Genetics Home Reference Wikipedia Leukodystrophy Care Network [huntershope.org]

Full text links Group 7SearchHeart failure treatmentPapersTopicsCollectionsEffects of Sodium-Glucose Cotransporter 2 Inhibitors for the Treatment of Patients With Heart Failure Importance: Only 1 class of glucose-lowering agents-sodium-glucose cotransporter [read.qxmd.com]

There are treatments that can be offered. What are the treatments for Coats’ disease? The child may be offered laser treatment. The laser is targeted at the abnormal blood vessels, at the point where they are leaking, which causes them to seal up. [gosh.nhs.uk]

Diagnosis - Coats plus syndrome Prognosis - Coats plus syndrome Treatment - Coats plus syndrome Resources - Coats plus syndrome Not supplied. [checkorphan.org]

Diagnosis and Prognosis: Ophthalmologists, neurologists, pediatricians, and orthopedists are likely to collaborate in the diagnosis and care of patients with this condition. Individuals must be monitored for spontaneous hemorrhages. [disorders.eyes.arizona.edu]

Prognosis The prognosis depends on the extent of the disease with milder, older presenting cases, having a better prognosis, of even spontaneous regression, whereas children under the age of three have a poorer prognosis. [eyewiki.aao.org]

The etiology of renal failure was not discovered, and the patient was being worked up for a kidney transplant. The patient required admission after deterioration of nutritional status with a BMI of 14.3. [miami.pure.elsevier.com]

Its precise genetic etiology was discovered in 2012: autosomal recessive mutation of the CTC1 gene. Publications about this syndrome are very few, and consist only of case reports, or small series of cases. [clinicaltrials.gov]

These characteristics help to clearly identify ROP as a causative etiology. The classic finding in FEVR is peripheral retinal capillary nonperfusion. [reviewofophthalmology.com]

In conclusion, the etiology of LCC remains unknown. In spite of relatively characteristic findings in imaging and histopathological examination, there is no uniformity in the clinical findings noted in the published articles. [scielo.br]

Based on histopathologic findings, some authors believe that cerebral microangiopathy is the possible etiology of LCC [ 6, 12 ]. [link.springer.com]

"A Population-Based Study of Coats Disease in the United Kingdom I: Epidemiology and Clinical Features at Diagnosis." Eye 24 Dec. 2010: 1797-1801. [medicinenet.com]

This in turn can cause secondary glaucoma, cataract and, ultimately, blindness of the eye.[1][2] Epidemiology[edit] This syndrome is usually sporadic although families with two or more affected siblings of both sexes are known.[1][3] History[edit] A child [en.wikipedia.org]

Epidemiology Brown’s syndrome is not uncommon, accounting for 1 of every 450 cases of congenital strabismus. It affects either eye or either sex equally and is bilateral in 10% (2, 7, 8). [neuroophthalmology.ca]

[…] pseudoaneurysm in a child (caused by a hydatid cyst ) Risk factors are similar for almost all lung cancers and include the following: Prolonged asbestos exposure Exposure to industrial elements (eg, gold, nickel) Tobacco smoking Secondary smoke exposure Epidemiology [emedicine.medscape.com]

Nathan and Oski’s is the only comprehensive product on the market that relates pathophysiology in such depth to hematologic and oncologic diseases affecting children. [books.google.com]

It is caused by compound heterozygous mutations in the conserved telomere maintenance component 1 (CTC1) gene, but its exact pathophysiology is still not well understood. [checkorphan.org]

This review summarizes the pathophysiology underlying TBDs, associated clinical features, management recommendations and therapeutic options. [tandfonline.com]

Symptoms - Coats plus syndrome Causes - Coats plus syndrome Prevention - Coats plus syndrome Not supplied. Diagnosis - Coats plus syndrome Prognosis - Coats plus syndrome Treatment - Coats plus syndrome Resources - Coats plus syndrome Not supplied. [checkorphan.org]

To prevent telomere shortening, telomerase, a ribonucleoprotein enzyme, extends telomeres by reverse transcription. This is crucial for telomere length maintenance in germ cells, stem cells and cancers. [imb.sinica.edu.tw]

Other treatments are designed to prevent or lessen complications of GBS. [encyclopedia.com]

Identification of therapeutic strategies that may prevent the aggregation of these proteins and rescue dysfunctional cells has been stressed. [ncbi.nlm.nih.gov]

The primary aim of treatment is to prevent further deterioration in vision as a result of fluid reaching the central retina (macula). [gosh.nhs.uk]