Cerebroretinal microangiopathy with calcifications and cysts is a very rare inherited disease that mainly damages the tiny blood vessels in the brain and the back of the eye (the retina). It causes three typical brain changes that doctors see on scans: white-matter damage (leukoencephalopathy), many small calcium deposits (calcifications), and fluid-filled spaces (cysts). At the same time, the retinal vessels become abnormal and leaky, which can seriously affect vision. The condition also often involves the bones, blood, stomach and intestines, liver, skin, hair and nails, so it is considered a multisystem disorder.
Cerebroretinal microangiopathy with calcifications and cysts (CRMCC), also called Coats plus syndrome, is a rare inherited disease where tiny blood vessels in the brain and retina become abnormal, fragile, and leaky. Over time this causes white-matter damage, brain calcifications and cysts, serious eye disease, bone weakness, gut bleeding, anemia, and growth problems.
CRMCC is usually caused by harmful changes in the CTC1 gene (and sometimes related CST-complex genes like STN1 or POT1), which help maintain chromosome ends (telomeres). When this system fails, small vessels and many tissues age or scar too early, leading to progressive neurologic, retinal, bone, and gastrointestinal complications from childhood or adolescence.
This disease belongs to a group called “telomere biology disorders.” In these disorders, genes that normally protect the ends of chromosomes (telomeres) do not work properly. In cerebroretinal microangiopathy with calcifications and cysts, the main problem is usually harmful changes (mutations) in the CTC1 gene, which is part of a protein complex (CST complex) that helps maintain telomeres. When this system fails, cells that divide a lot, such as those in small blood vessels, bone marrow and bone, become weak and damaged, leading to the wide range of symptoms seen in this disease.
Other names
Cerebroretinal microangiopathy with calcifications and cysts is known by several different names in the medical literature. All of these labels describe the same or very closely related conditions, so doctors often treat them as one disease spectrum.
Coats plus syndrome – This is the most common alternative name. “Coats” refers to Coats disease, a retinal condition with leaky abnormal vessels and exudative retinal detachment. “Plus” indicates that in this syndrome, similar eye findings occur together with brain calcifications, cysts, white-matter changes, and systemic features such as bone and gut problems.
CRMCC (CerebroRetinal Microangiopathy with Calcifications and Cysts) – This is the usual short form used in research articles. “Cerebro” refers to the brain, “retinal” to the eyes, “microangiopathy” to small blood-vessel disease, and “calcifications and cysts” describe the typical brain imaging findings.
Cerebroretinal microangiopathy with calcifications and cysts 1 / 2 / 3 (CRMCC1, CRMCC2, CRMCC3) – These names are used when doctors want to be very precise about which gene is affected. Type 1 usually refers to CTC1-related disease, type 2 to STN1-related disease, and type 3 to POT1-related disease, all of which disturb the same telomere-maintenance pathway.
Types
Doctors can group this disease in different ways. One useful way is by the exact gene that is mutated. Another useful way is by the clinical pattern (for example, classic childhood-onset disease versus later onset, eye-sparing forms).
Type 1: CTC1-related CRMCC (CRMCC1)
In this type, both copies of the CTC1 gene are mutated. This is the “classic” Coats plus / CRMCC form, usually starting in infancy or early childhood with eye symptoms, brain changes, growth problems, bone fragility and anemia. CTC1 encodes a key part of the CST complex, so mutations here strongly impair telomere maintenance in many tissues.
Type 2: STN1-related CRMCC (CRMCC2)
Here, mutations affect the STN1 gene, which encodes another CST complex component. Patients often look very similar to those with CTC1 mutations, including retinal vascular disease, brain calcifications and cysts, and sometimes bone marrow and liver problems. Recognizing STN1 as a cause shows that disruption of the whole CST complex, not just CTC1 alone, can lead to this syndrome.
Type 3: POT1-related CRMCC (CRMCC3)
In this type, POT1 gene variants disturb another telomere-protecting complex called shelterin. These patients share the core features of white-matter disease, brain calcifications, and cysts, but the exact pattern of eye and systemic problems can vary. Grouping them as CRMCC3 highlights that several telomere genes can converge on a similar cerebroretinal small-vessel disease.
Clinical variants (classic childhood-onset vs late-onset)
Most patients are diagnosed in childhood with eye symptoms and widespread systemic features. However, some people with CTC1 mutations present later in life, sometimes with brain changes but relatively mild or absent eye findings. This suggests a spectrum, from severe early disease with many organs involved to milder adult forms where changes are more limited to the brain.
Causes and disease mechanisms
Before listing the causes, it is important to say clearly that the main root cause is inherited gene mutations, not infection, diet, or lifestyle. The 20 “causes” below therefore describe the genetic changes, inheritance pattern, and biological mechanisms that together produce the disease.
-
Biallelic CTC1 mutations
Most patients have two disease-causing changes in the CTC1 gene (one from each parent), which severely disrupt the CST complex and telomere maintenance. This is the best-documented direct cause of classic cerebroretinal microangiopathy with calcifications and cysts. -
Biallelic STN1 mutations
Some families have mutations in STN1 instead of CTC1. STN1 partners with CTC1 and TEN1 to form the CST complex, so STN1 defects cause very similar telomere and vessel problems, leading to a nearly identical clinical picture. -
Biallelic POT1 mutations
In other families, harmful changes in POT1, another telomere-binding protein, have been linked to CRMCC3. POT1 defects destabilize telomere ends, making vascular and bone-marrow cells more vulnerable to damage and cell death. -
Autosomal recessive inheritance
The disease follows an autosomal recessive pattern. This means a child must inherit one faulty gene copy from each parent. Parents are usually healthy carriers with one normal and one mutated copy, but when both are carriers, each pregnancy has a one-in-four chance of producing an affected child. -
Carrier parents and family history
Having carrier parents, especially in families with known cases of Coats plus / CRMCC or related telomere biology disorders, is a strong risk factor. Brothers and sisters of an affected child have a higher chance of being carriers or also affected. -
CST complex dysfunction
CTC1 and STN1 mutations weaken the CST complex, which normally binds single-stranded DNA at telomeres and helps complete DNA replication. When CST does not work properly, telomeres become too short or unstable, affecting cell survival in many organs. -
Telomere shortening in endothelial cells
Endothelial cells line small blood vessels in the brain and retina. In telomere disorders, their telomeres shorten too quickly, making these cells fragile. Over time, this contributes to microangiopathy, leaking vessels, calcifications, and cyst formation in the brain and eyes. -
Telomere damage in bone-marrow stem cells
Bone-marrow stem cells divide often to produce blood cells. Short, unstable telomeres in these cells can lead to bone-marrow failure, anemia and low platelets, which are common in Coats plus / CRMCC and related telomere biology conditions. -
Telomere‐related defects in bone-forming cells
Osteoblasts (bone-forming cells) also rely on healthy telomeres. When telomere function is poor, bones become thin and fragile (osteopenia), and fractures occur more easily, especially in the long bones of the legs. -
Abnormal development of brain microvasculature
During early brain development, small arteries and capillaries may not form normally because of telomere-related cell injury. This abnormal microvasculature is linked to the later appearance of calcifications, cysts, and white-matter changes on brain imaging. -
Breakdown of the blood-retinal barrier
In the retina, damaged endothelial cells lose their tight barrier function. Fluid and lipids leak out of vessels into and under the retina, creating exudative retinal detachment that closely mimics Coats disease. -
Microangiopathy of the gastrointestinal tract
Small abnormal vessels in the stomach and intestines can become thin-walled, enlarged and leaky, causing recurrent intestinal bleeding in many patients. This microangiopathy is a direct result of the same telomere-driven small-vessel damage seen in the brain and eyes. -
Portal hypertension and liver vascular damage
Telomere damage in hepatic vessels can lead to vascular malformations and scarring in the liver, sometimes causing portal hypertension and liver failure in Coats plus / CRMCC. These complications further increase the risk of bleeding and poor overall health. -
Placental and fetal vascular stress
Many affected babies grow poorly before birth and are born preterm. Abnormal telomere biology in the fetoplacental circulation likely contributes to this growth restriction and pregnancy complications such as high blood pressure and pre-eclampsia in the mother. -
Chronic low-grade brain injury from leukoencephalopathy
White-matter changes represent chronic damage to brain wiring. Although this is a consequence rather than a primary cause, ongoing leukoencephalopathy feeds back into disease progression by causing seizures, cognitive decline and movement problems, which then increase disability and vulnerability to infections. -
Genetic heterogeneity of telomere biology disorders
CTC1, STN1 and POT1 are part of a broader group of telomere genes. In some patients, variants in more than one telomere-related gene may modify disease expression, making symptoms more severe or changing which organs are most affected. -
Consanguinity (parents related by blood)
In populations where marriages between relatives are more common, the chance that both parents carry the same rare recessive mutation is higher. This increases the risk of having a child with CRMCC or related telomere biology disorders. -
De novo (new) mutations in telomere genes
Although many cases occur in families, some harmful variants can appear for the first time in an affected child (de novo). In these situations, neither parent has symptoms, but the child still develops CRMCC because a new mutation arose in early development. -
Telomere-driven genomic instability
Very short or unprotected telomeres can lead to chromosome breaks and abnormal repair. This genomic instability further harms highly active tissues like bone marrow and vessel walls, reinforcing the small-vessel disease and bone-marrow failure that characterize Coats plus / CRMCC. -
Lack of effective telomere repair reserve
In healthy people, telomere maintenance pathways provide some “reserve” capacity to recover from environmental stress (for example infections or inflammation). In CRMCC, this reserve is already very low, so everyday stresses can more easily tip cells over into dysfunction and death, making the disease progressive even without a clear external trigger.
Symptoms and signs
Because this disease affects the brain, eyes, bones, gut, liver, blood and skin, symptoms can be very varied. Below are 15 key symptoms and signs explained in simple language.
-
Poor growth before and after birth
Many babies with this condition grow more slowly than expected in the womb and remain small as children. They may have low birth weight, shorter height, and a smaller than average head size. -
Preterm birth
A significant number of affected babies are born early. Prematurity can add extra stress to the brain, lungs and eyes, which may worsen the course of the disease and complicate early care. -
Vision problems and white pupil (leukocoria)
Children often present with poor vision, a white reflex in the pupil, eye redness or irritation. These changes result from abnormal, leaky retinal vessels, retinal detachment and sometimes high pressure in the eye (glaucoma). -
Retinal detachment and exudative retinopathy
Fluid and fatty material leak from diseased retinal vessels and collect under the retina. This pushes the retina off the back of the eye (detachment) and can lead to sudden drops in vision or permanent blindness if not treated. -
Seizures (epileptic fits)
Because the white matter and deep brain structures are damaged, many patients develop partial or generalized seizures. Seizures may first appear in childhood or adolescence and can become more frequent as the disease progresses. -
Spasticity and stiffness of the limbs
Damage to the motor pathways in the brain causes increased muscle tone, tightness and exaggerated reflexes, especially in the legs. This spasticity can make walking difficult and may require physical therapy or assistive devices. -
Ataxia and unsteady gait
Lesions in the cerebellum and its connections lead to ataxia—clumsiness, poor balance and unsteady, wide-based walking. Children may fall frequently, have trouble running, or struggle with fine motor tasks such as writing. -
Cognitive impairment and learning difficulties
Progressive white-matter damage and cysts can affect thinking skills. Problems often start with visuospatial and constructional tasks (for example puzzles or drawing), but over time, broader learning difficulties and slower processing can appear. -
Headaches and symptoms of raised intracranial pressure
When brain cysts enlarge or when swelling is present, intracranial pressure may rise. Patients can then experience headaches, nausea, vomiting, or visual changes related to pressure on brain structures and optic nerves. -
Recurrent intestinal bleeding
Small fragile vessels in the stomach and intestines can bleed repeatedly. Families may notice dark or bloody stools, vomiting of blood, or unexplained anemia. Severe bleeding attacks may require hospital care and blood transfusions. -
Anemia with tiredness and pallor
Many patients develop anemia, often macrocytic. They can look pale, tire easily, feel breathless with mild activity, and may need repeated transfusions if the bone marrow cannot keep up. -
Easy bruising and low platelets (thrombocytopenia)
Low platelet counts make bruises and small skin bleeds appear easily, and nosebleeds or bleeding from gums may be frequent. This adds to the risk when intestinal bleeding or surgery occurs. -
Bone pain and fractures
The long bones, especially in the legs, are often thin and fragile (osteopenia). Children may break bones after minor falls, complain of bone pain, or show X-ray changes such as metaphyseal sclerosis and flaring. -
Skin, hair and nail changes
Some patients have sparse or prematurely greying hair, café-au-lait skin spots, or brittle, ridged nails. These features overlap with other telomere biology disorders such as dyskeratosis congenita and show that the disease affects the whole body, not only the brain and eyes. -
General failure to thrive and fatigue
Combining poor growth, anemia, chronic neurological problems and recurrent bleeding, many children show general failure to thrive. They may eat poorly, gain weight slowly and have limited energy for normal play and school activities.
Diagnostic tests
Diagnosis usually combines clinical examination, detailed imaging of the brain and eyes, blood and bone-marrow tests, and confirmation with genetic studies. Below are 20 important tests, grouped by type.
Physical exam–based tests
-
General growth and vital-signs assessment
The doctor measures height, weight, head circumference and body proportions, and checks heart rate, blood pressure and temperature. Children with CRMCC often show short stature, low weight and signs of chronic illness, which guide further investigation. -
Detailed neurological examination
This exam checks muscle tone, reflexes, strength, coordination, eye movements and speech. Findings such as spasticity, ataxia, abnormal reflexes and cranial-nerve signs suggest a central nervous system disorder and support the need for brain imaging. -
Systemic physical exam including abdominal and stool check
The clinician feels the abdomen for enlarged liver or spleen, looks for signs of portal hypertension, and may check stool for hidden blood. These simple steps help detect gastrointestinal bleeding and liver involvement, which are common systemic features. -
Bedside eye examination
Using a light and basic tools, the doctor inspects the pupils, cornea and front part of the eye and looks for leukocoria, redness or abnormal reflexes. Suspicious findings prompt more detailed retinal imaging to look for Coats-like changes.
Manual / functional tests
-
Visual acuity and visual field testing
Age-appropriate charts, pictures or finger-counting are used to measure how well the patient sees in each eye and whether parts of the visual field are missing. Reduced central or peripheral vision can reflect retinal detachment or optic-pathway damage from brain lesions. -
Coordination and gait tests
Simple bedside tests such as finger-to-nose, heel-to-shin, standing with feet together, and walking along a straight line help detect ataxia and balance problems. These signs point to cerebellar and white-matter involvement, typical of CRMCC. -
Muscle strength and tone testing
The examiner gently resists limb movements and checks how easily joints move. Increased tone with “catchy” movement and weakness in certain muscle groups indicate pyramidal-tract damage, consistent with leukoencephalopathy and brain calcifications. -
Developmental and cognitive screening
Standard checklists and simple tasks assess speech, fine motor skills, school performance and problem-solving. Delays, especially in visuospatial skills, support the suspicion of a chronic brain disorder and help track disease progression over time.
Lab and pathological tests
-
Complete blood count (CBC) and blood smear
CBC often reveals anemia and sometimes low platelets. The blood smear may show large red cells or other changes that suggest bone-marrow stress or failure, which is common in telomere biology disorders including Coats plus / CRMCC. -
Coagulation profile and basic metabolic panel
Tests such as prothrombin time, activated partial thromboplastin time, liver enzymes and kidney function help evaluate bleeding risk and organ involvement. Abnormal results may reflect chronic intestinal bleeding or liver disease related to portal hypertension. -
Iron, vitamin B12 and folate levels
These help distinguish anemia due to nutrient deficiency from anemia due to bone-marrow failure. In CRMCC, macrocytic anemia often reflects intrinsic bone-marrow problems rather than simple deficiency, guiding doctors away from overly simple explanations. -
Genetic testing for CTC1, STN1, POT1 and related genes
DNA from blood or saliva is sequenced to look for disease-causing variants in CTC1, STN1, POT1 and sometimes other telomere genes. Finding biallelic pathogenic variants in one of these genes is the strongest confirmation of CRMCC and helps with family counseling. -
Telomere length analysis in leukocytes
Special tests measure telomere length in white blood cells. Many telomere biology disorders show very short telomeres for age, and while this test is not specific, it supports the diagnosis and may prompt more detailed gene testing. -
Bone-marrow aspiration and biopsy
Taking a small sample of bone marrow allows doctors to see whether the marrow is underactive, shows megaloblastic changes, or has other features of telomere biology disorders. This is important in patients with severe anemia or thrombocytopenia.
Electrodiagnostic tests
-
Electroencephalogram (EEG)
EEG records the brain’s electrical activity. In CRMCC, EEG may show abnormal discharges or focal slowing related to seizures and white-matter lesions. This helps confirm epilepsy and guides choice of anti-seizure medications. -
Visual evoked potentials (VEPs)
VEPs measure the brain’s response to visual stimuli. They can show delayed or reduced signals when the optic pathways are damaged by white-matter disease or when severe retinal disease interferes with visual input, adding functional information to imaging.
Imaging tests
-
Brain CT scan
A non-contrast CT of the head is one of the most characteristic tests. It typically shows widespread intracranial calcifications in the cerebral white matter, basal ganglia, thalami and brainstem. This pattern, together with cysts, is highly suggestive of CRMCC. -
Brain MRI (including FLAIR and T2 sequences)*
MRI reveals diffuse or patchy white-matter changes and multiple brain cysts, especially in the thalami and surrounding regions. T2* or susceptibility-weighted sequences help distinguish calcifications and microbleeds, completing the typical triad of leukoencephalopathy, calcifications and cysts. -
Skeletal radiographs / bone survey
X-rays of the long bones often show osteopenia and characteristic metaphyseal changes, such as sclerosis and flaring near the ends of the femur and tibia. These bone findings support the diagnosis and help distinguish CRMCC from brain-only disorders. -
Retinal imaging (ophthalmoscopy, fluorescein angiography, OCT)
Detailed examination of the retina with ophthalmoscopy, fluorescein angiography and optical coherence tomography shows abnormal, tortuous and dilated peripheral vessels, areas of non-perfusion, leakage and exudative retinal detachment. This Coats-like retinal picture, together with the brain triad, is a hallmark of Coats plus / CRMCC.
Non-pharmacological treatments
-
Low-vision rehabilitation
Specialist low-vision services teach children and families how to use remaining sight with optical aids, contrast enhancement, large print, magnifiers, and lighting optimization. This can help school performance, mobility, and independence even when retinal damage from CRMCC cannot be reversed. -
Regular ophthalmologic monitoring
Frequent visits to a retinal specialist allow early detection of telangiectatic vessels, exudation, and retinal detachment. Careful imaging guides the timing of laser or surgical treatment before permanent vision loss or painful complications like secondary glaucoma develop. -
Physiotherapy for spasticity and ataxia
Physiotherapists use stretching, strengthening, balance, and gait training to reduce stiffness, improve coordination, and maintain walking in children with spasticity, dystonia, or cerebellar signs from brain calcifications and leukodystrophy. This lowers contracture risk and helps daily function. -
Occupational therapy (OT)
OT focuses on hand skills, self-care (dressing, feeding, writing), and environmental adaptations. Simple aids, splints, and activity planning help children with weakness, tremor, or visual loss participate better in school and home life, while also supporting caregivers. -
Speech and language therapy
Brain involvement can cause dysarthria, language delay, and swallowing difficulty. Speech therapists work on clear articulation, understanding and expression, safe swallowing strategies, and communication devices, helping reduce aspiration risk and supporting learning. -
Swallowing and nutrition assessment
Dietitians and speech therapists evaluate chewing, swallowing, and calorie intake. They suggest food textures, thickened liquids, feeding positions, and high-calorie meal plans, or consider feeding tubes if weight gain is poor or aspiration risk is high. -
Fracture-prevention and bone-health program
Because osteopenia and pathological fractures are common, teams use fall-prevention training, safe transfer techniques, and weight-bearing exercises within limits. They may recommend braces or protective gear to lower fracture risk during play and physiotherapy. -
Endoscopic management of gastrointestinal bleeding
Gastroenterologists use endoscopy to identify telangiectatic intestinal vessels causing chronic or acute bleeding. Techniques such as argon plasma coagulation or clipping can reduce bleeding episodes and limit transfusion needs in selected patients. -
Transfusion support programs
Structured red-cell and platelet transfusion plans help treat symptomatic anemia and thrombocytopenia while monitoring iron overload. Transfusions improve energy, growth, and bleeding control, but require careful infection and iron-burden surveillance. -
Seizure-safety education
Families learn seizure first-aid, supervision near water or heights, and when to call emergency services. This non-drug education reduces injury risk and anxiety around epilepsy that is common in CRMCC. -
Intracranial pressure monitoring and neurosurgical planning
For large brain cysts causing headaches, vomiting, or decline, neurosurgeons monitor signs of raised intracranial pressure and plan timely interventions like cyst fenestration or shunting. Non-drug monitoring helps avoid sudden decompensation. -
Orthopedic bracing and postural management
Spinal and limb deformities from muscle imbalance or fractures may benefit from orthoses, standing frames, and posture programs. These support more comfortable sitting, standing, and reduce pressure sores. -
Psychological and family counseling
Living with a rare, progressive disorder is stressful. Psychologists can help children and caregivers cope with chronic illness, grief, and uncertainty, while supporting adherence to complex treatment plans. -
Educational support and special schooling
Neurocognitive and visual impairment often require individualized education plans, large-print materials, assistive technology, and extra time for exams. Early collaboration with schools improves educational outcomes. -
Palliative care integration
Palliative care teams focus on symptom relief (pain, spasticity, breathlessness, anxiety) and family support at any disease stage, not only end-of-life. Their goal is comfort and quality of life alongside active treatments. -
Vaccination and infection-prevention measures
Standard childhood vaccines, plus extra vaccines recommended by specialists, help reduce infections that could worsen anemia, bone marrow suppression, or neurological status in CRMCC. Good hand hygiene and prompt infection treatment are also important. -
Fall-prevention and home safety modifications
Simple adaptations—grab bars, non-slip floors, good lighting, removing trip hazards—reduce falls in children with visual loss, ataxia, or spasticity and therefore lower fracture and head-injury risk. -
Pain management with non-drug techniques
Heat packs, gentle massage, stretching, positioning, and relaxation techniques can reduce musculoskeletal pain from spasticity or fractures and complement medication-based pain relief. -
Genetic counseling for families
Because CRMCC is usually autosomal recessive, genetic counselors explain inheritance, recurrence risk in future pregnancies, and options for carrier testing or prenatal diagnosis in families with a known CTC1 or related mutation. -
Participation in registries and research
Enrolling in rare-disease registries and clinical studies helps families access emerging diagnostic tools and experimental treatments, and contributes to better understanding and management of CRMCC worldwide.
Drug treatments
⚠️ Important: No medicine is currently licensed specifically for CRMCC. Drugs are used off-label to manage seizures, eye disease, bone problems, and gut bleeding, based on small case reports and on experience from other conditions. Doses must always be individualized by specialists using official prescribing information (for example FDA labels) and local guidelines.
-
Levetiracetam (KEPPRA) – antiepileptic
Levetiracetam is often chosen as first-line add-on treatment for partial and generalized seizures because it has relatively few drug interactions and is available as oral and IV forms. Typical labeled adult doses range from 500–1500 mg twice daily, adjusted by weight and kidney function, but exact dosing in CRMCC should be set by a neurologist. Common side effects include drowsiness, dizziness, mood changes, and irritability. -
Valproate (sodium valproate/divalproex) – broad-spectrum antiepileptic
Valproate helps control generalized seizures and myoclonus, which may occur with CRMCC-related cortical damage. It is usually given in multiple divided doses based on mg/kg. Doctors monitor liver function, platelet counts, and drug levels, because serious side effects include liver toxicity, pancreatitis, weight gain, and teratogenicity. -
Lamotrigine – antiepileptic and mood stabilizer
Lamotrigine can be used for focal and generalized seizures and may be added when levetiracetam or valproate alone are insufficient. It must be titrated slowly from a very low dose to avoid serious skin reactions such as Stevens–Johnson syndrome. Headache, dizziness, and insomnia are other common side effects. -
Clonazepam or diazepam – benzodiazepines for seizure clusters
Short-acting benzodiazepines are used as rescue medicines for prolonged seizures or clusters. They work quickly by enhancing GABA in the brain, but cause sedation and may depress breathing at high doses, so they are used under close medical supervision and not as daily long-term monotherapy. -
Baclofen – oral antispasticity drug
Baclofen reduces muscle stiffness and spasms by acting on spinal GABA-B receptors. It is started at low doses and increased slowly to balance benefit against drowsiness, weakness, and nausea. Sudden withdrawal can cause severe rebound spasticity, so tapering must be supervised. -
Tizanidine – antispasticity agent
Tizanidine is an alpha-2 adrenergic agonist that decreases reflex muscle activity and can improve comfort in patients with CRMCC-related spasticity. It is usually taken several times per day, with liver-function and blood-pressure monitoring due to risks of hypotension, sedation, and liver enzyme elevation. -
Botulinum toxin injections – focal spasticity treatment
In selected muscles causing contractures or pain, injected botulinum toxin temporarily weakens overactive muscles for several months. This can improve limb position, ease care, and enhance the effects of physiotherapy. Side effects are usually localized weakness and pain at the injection site. -
Bevacizumab (AVASTIN and similar products) – anti-VEGF agent
Bevacizumab is a monoclonal antibody against VEGF, used systemically for cancers and intravitreally for eye disease. Case reports and related leukoencephalopathy with calcifications and cysts suggest that VEGF blockade may shrink brain cysts and reduce vascular leakage, but this is experimental in CRMCC and has serious risks such as bleeding, hypertension, and impaired wound healing. -
Other intravitreal anti-VEGF agents (ranibizumab, aflibercept)
These newer anti-VEGF injections are widely used for retinal vascular diseases. In Coats-like retinopathy they may help reduce exudation and macular edema when combined with laser or surgery, although data in CRMCC are limited to small series. Risks include endophthalmitis, intraocular pressure rise, and systemic VEGF suppression. -
Acetazolamide – carbonic anhydrase inhibitor
Acetazolamide can lower intracranial pressure and treat some forms of headache or papilledema by reducing cerebrospinal-fluid production. It is given orally in divided doses, with monitoring of electrolytes and kidney function because it can cause metabolic acidosis, kidney stones, and tingling sensations. -
Topiramate – antiepileptic and migraine-preventive drug
Topiramate helps control focal and generalized seizures and may reduce migraine-like headaches described in CRMCC. It is titrated slowly to reduce side effects such as cognitive slowing, weight loss, kidney stones, and paresthesias. Adequate hydration is essential. -
Pantoprazole (PROTONIX) – proton-pump inhibitor
Pantoprazole protects the stomach and upper gut from acid damage and is frequently used in patients with chronic gastrointestinal bleeding or after endoscopic treatment. Typical adult IV or oral doses are 40 mg once daily for limited periods, adjusted by indication, as described in FDA labeling; long-term use requires monitoring for infections, low magnesium, and bone effects. -
Sucralfate – mucosal protective agent
Sucralfate can coat irritated mucosa in the upper gastrointestinal tract and may be used alongside PPIs to reduce bleeding from erosions. Because it can bind other drugs, dosing must be spaced from important medicines. Constipation and aluminum accumulation in renal impairment are main concerns. -
Octreotide – somatostatin analogue for GI bleeding
Octreotide reduces splanchnic blood flow and can help control certain forms of gastrointestinal bleeding or portal hypertension. It is given by injection or continuous infusion under hospital monitoring, with possible side effects including gallstones, abdominal pain, and glucose changes. -
Tranexamic acid – antifibrinolytic
Tranexamic acid stabilizes blood clots by blocking fibrinolysis and may be used short term in severe mucosal bleeding under specialist guidance. It is given orally or IV with dosing based on weight and renal function; risks include thrombosis and seizures at high doses. -
Oral iron therapy (e.g., ferrous sulfate)
Chronic intestinal bleeding frequently causes iron-deficiency anemia. Oral iron supplements, taken once or multiple times per day with vitamin C-rich fluids, can rebuild iron stores over months. Common side effects are dark stools, constipation, or nausea, so dosing may need adjustment. -
Intravenous iron preparations
In children or adults with poor absorption, intolerance to oral iron, or severe anemia, IV iron formulations allow quicker iron repletion under careful monitoring for infusion reactions. They are given in weight-based doses spaced over several sessions. -
Folate and vitamin B12 supplementation
Macrocytic anemia and bone-marrow abnormalities have been described in CRMCC. When deficiency is documented, doctors give folic acid and/or vitamin B12 in specific doses and routes to normalize red-cell production and reduce anemia-related fatigue. -
Erythropoiesis-stimulating agents (ESAs)
In selected cases with chronic anemia not correctable by iron alone, ESAs such as epoetin alfa or darbepoetin may be considered to stimulate red-cell production, with strict monitoring for hypertension and thrombosis. Use is highly specialized and often reserved for defined indications. -
Broad-spectrum antibiotics when sepsis is suspected
Because gut bleeding, transfusions, and invasive procedures raise infection risk, early broad-spectrum IV antibiotics are vital when fever or sepsis signs appear. Choices depend on local patterns and guidelines, and therapy is quickly narrowed once cultures return.
Dietary molecular supplements
-
Vitamin D3
Vitamin D3 supports calcium absorption, bone mineralization, and muscle function, which is crucial in CRMCC patients with osteopenia and fractures. Dosing follows age- and level-based guidelines, with blood-level monitoring to avoid deficiency or toxicity. -
Calcium (preferably citrate or carbonate with meals)
Calcium supplements help maintain bone density when dietary intake is low or bones are fragile. Doctors choose total daily elemental calcium based on age and diet, dividing doses and monitoring kidney function and urine for stones. -
Oral iron (as molecular supplement for deficiency)
Beyond therapeutic doses, lower-dose iron supplements can maintain iron stores once anemia is corrected, especially if small ongoing GI blood losses persist. They must be balanced with side effects and taken away from certain medicines. -
Folic acid
Folic acid supports DNA synthesis and red-blood-cell production. Supplementation is important when macrocytosis or poor dietary intake is documented, with typical daily doses determined by age and lab results. -
Vitamin B12
Vitamin B12 works with folate in red-cell production and nervous-system health. In proven deficiency, oral high-dose or injectable B12 is used; levels and neurologic symptoms are monitored to ensure effective replacement. -
Omega-3 fatty acids (fish-oil or algae-based)
Omega-3 supplements may have anti-inflammatory and neuroprotective effects and can support cardiovascular health. They are generally well tolerated but can increase bleeding risk at high doses, so they must be reconciled with any anticoagulant or antiplatelet therapy. -
Antioxidant vitamins (C and E)
Antioxidants help limit oxidative stress, which may contribute to progressive tissue damage in telomere-related disorders, though direct evidence in CRMCC is limited. Moderate supplemental doses, not mega-doses, are usually preferred to avoid potential harm. -
Coenzyme Q10
CoQ10 supports mitochondrial energy production and has been explored in other neurologic and mitochondrial disorders. In CRMCC it may be tried as an adjunct under specialist guidance, with doses adjusted for age and weight; side effects are usually mild gastrointestinal upset. -
Zinc
Zinc is important for immune function, wound healing, and growth. Supplementation may be considered when dietary intake is poor or lab tests show deficiency, but excessive zinc can disturb copper balance, so monitoring is essential. -
Probiotics and prebiotic fibre
Probiotic bacteria and soluble fibre can support gut health, which may be beneficial in patients with chronic intestinal disease and bleeding. Choice of product and dose is individualized, especially when the immune system is weakened.
Immunity-booster, regenerative and stem-cell–related drugs
-
Filgrastim or pegfilgrastim (G-CSF)
Granulocyte colony-stimulating factors increase neutrophil production and may be used transiently when severe neutropenia or marrow suppression is present, usually around infections or chemotherapy. Doses are weight-based and require close monitoring for bone pain and rare splenic complications. -
Eltrombopag or romiplostim (TPO-receptor agonists)
These agents stimulate platelet production in certain chronic thrombocytopenias. In CRMCC they would only be considered in highly selected cases with refractory low platelets, after thorough risk–benefit assessment because of possible liver toxicity and thrombotic events. -
Epoetin alfa / darbepoetin alfa (ESAs)
By stimulating bone-marrow erythroid cells, ESAs can reduce transfusion needs in some forms of chronic anemia. In telomere-related marrow disease they must be used cautiously with careful blood-pressure and thrombotic-risk monitoring. -
Intravenous immunoglobulin (IVIG)
IVIG provides pooled antibodies that can modulate immune responses and help treat certain immune-mediated cytopenias or recurrent infections. It is given as intermittent infusions with monitoring for headache, kidney effects, and rare thrombotic events. -
Immunosuppressive agents (e.g., cyclosporine, anti-thymocyte globulin)
In severe marrow failure overlapping with aplastic anemia, regimens using drugs like ATG and cyclosporine have been used in related telomere disorders or before hematopoietic stem-cell transplant (HSCT). These powerful agents require expert centers, infection prophylaxis, and long-term monitoring. -
Hematopoietic stem-cell transplantation (HSCT)–related drugs
When HSCT is considered for life-threatening marrow failure in CRMCC, conditioning regimens (for example fludarabine-based reduced-intensity protocols) and graft-versus-host-disease prophylaxis drugs are used. Published CRMCC cases show HSCT is possible but high-risk, so it is reserved for very severe situations in specialized centers.
Surgeries and procedures
-
Retinal laser photocoagulation or cryotherapy
Eye surgeons use laser or freezing to close abnormal telangiectatic vessels in the retina, aiming to stop leakage and prevent or limit exudative detachment. This is often performed under anesthesia and may require repeated sessions as disease progresses. -
Vitrectomy and retinal reattachment surgery
In advanced cases with traction or total retinal detachment, pars plana vitrectomy, scleral buckling, or combined procedures may be needed to reattach the retina and salvage any remaining vision. Risks include cataract, glaucoma, and recurrent detachment. -
CSF shunt or cyst fenestration
If brain cysts lead to raised intracranial pressure, neurosurgeons may insert shunts or surgically open cysts to relieve pressure. The goal is to prevent further neurologic decline and relieve headaches, but infection and shunt malfunction are important risks. -
Orthopedic fracture fixation and deformity correction
Surgical fixation of long-bone fractures or corrective osteotomies may be needed when osteopenic bones break or deform. These operations aim to restore alignment, enable weight-bearing, and reduce chronic pain and disability. -
Gastrointestinal surgery or advanced endoscopic therapy
For life-threatening or recurrent intestinal bleeding not controlled by medicine or standard endoscopy, segmental bowel resection or more aggressive endoscopic approaches may be required. The aim is to remove the bleeding focus while preserving bowel function.
Preventions
-
Early diagnosis and regular specialist follow-up
Prompt recognition of CRMCC and scheduled visits with neurology, ophthalmology, hematology, and gastroenterology teams help prevent many complications or catch them early. -
Vaccinations and infection control
Keeping vaccines up to date, practicing hand hygiene, and quickly treating infections may prevent severe illnesses that can worsen bone-marrow suppression or seizures. -
Bone-health support
Adequate calcium, vitamin D, supervised weight-bearing exercise, and avoidance of smoking in older patients help maintain bone strength and reduce fracture risk. -
Regular eye checks from infancy
Screening eyes early and often allows prompt laser or other treatments before irreversible retinal detachment and blindness develop. -
Avoiding unnecessary NSAIDs and blood-thinning drugs
Non-steroidal anti-inflammatory drugs and certain blood thinners can increase GI bleeding risk and should only be used when clearly needed and approved by specialists. -
Safe environment and fall-prevention
Home adaptations, mobility aids, and supervision reduce falls and fractures in patients with visual loss or balance problems. -
Seizure-trigger management
Regular sleep, medication adherence, and avoiding known individual seizure triggers where possible can lower seizure frequency. -
Nutritional monitoring
Routine weight, height, and lab checks (iron, vitamins, albumin) help detect malnutrition early, allowing timely diet or supplement changes to prevent severe deficiency states. -
Early treatment of GI symptoms
Reporting black stools, vomiting blood, or unexplained fatigue early enables fast evaluation and intervention before massive bleeding occurs. -
Family genetic counseling before future pregnancies
For affected families, preconception counseling and genetic testing can help plan future pregnancies and consider options like carrier testing or prenatal diagnosis.
When to see doctors urgently
People with CRMCC should seek urgent medical care if there are new or worsening seizures, sudden loss of vision or a white pupil, severe or persistent headache with vomiting, signs of raised intracranial pressure, any vomiting of blood or black/tarry stools, sudden severe abdominal pain, high fever with lethargy, unexplained bruising or bleeding, or inability to walk or feed as before. Regularly scheduled follow-ups are also essential even when the person seems stable.
What to eat and what to avoid
-
Emphasize iron-rich foods such as lean meat, beans, and leafy greens to support anemia management; avoid very low-iron diets or frequent fast foods with poor micronutrient content.
-
Include calcium and vitamin D foods like dairy or fortified alternatives and safe sun exposure; avoid excessive fizzy drinks, which may reduce bone health and displace nutritious beverages.
-
Offer high-protein meals (eggs, fish, pulses) to support growth and healing; avoid extreme low-protein or crash diets, which can worsen weakness and immune problems.
-
Provide plenty of fruits and vegetables for vitamins, antioxidants, and fibre; limit ultra-processed snacks high in sugar, salt, and unhealthy fats.
-
Use soft or modified textures if swallowing is difficult, such as mashed or finely chopped foods; avoid hard, dry, or crumbly foods that are easy to choke on.
-
Encourage adequate fluids (water, oral rehydration) to prevent dehydration and constipation; avoid sugary drinks and energy drinks, which add calories with little nutrition.
-
Combine iron-rich foods with vitamin C sources (like citrus or tomatoes) to improve absorption; avoid taking iron with large amounts of tea or coffee, which can reduce absorption.
-
Use healthy fats (olive oil, nuts, seeds) in moderate amounts to support energy intake; avoid very high-fat, fried foods that may worsen reflux or gut discomfort.
-
Follow any special diet plans from the care team, for example if there is liver disease or portal hypertension; avoid self-imposed restrictive diets that are not supervised by a dietitian.
-
Check supplement use with doctors so vitamins or herbs fit safely with prescribed medicines; avoid unregulated “miracle cures” advertised online that have no evidence and may harm the liver, kidneys, or bone marrow.
Frequently asked questions
-
Is cerebroretinal microangiopathy with calcifications and cysts the same as Coats plus syndrome?
Yes. CRMCC and Coats plus syndrome describe the same telomere-related multi-system disorder with brain calcifications and cysts, Coats-like retinal disease, and systemic features such as bone and gut involvement. -
What causes this disease?
Most patients have harmful variants in the CTC1 gene and sometimes in related CST-complex genes, which disturb telomere maintenance and make small vessels and tissues fragile and prone to scarring and calcification. -
How is CRMCC usually diagnosed?
Doctors combine clinical features (eye disease, neurologic signs, growth and bone problems), brain and retinal imaging, blood tests, and finally confirm the diagnosis with genetic testing for CTC1 or related genes. -
Is there a cure?
At present there is no medicine that corrects the underlying telomere defect. Treatment is supportive and complication-focused; HSCT may help some marrow-failure aspects but does not fully cure the multisystem disease. -
Can vision be saved?
Some children benefit from early retinal laser, cryotherapy, or surgery, and from intravitreal anti-VEGF agents in selected situations, which may preserve or improve vision. However, if detachment is advanced, vision loss can be permanent. -
Why are bones fragile in CRMCC?
Telomere dysfunction and chronic illness contribute to osteopenia; children often have low bone mineral density and are prone to fractures, especially in long bones, so bone-protective strategies are very important. -
Why does gastrointestinal bleeding happen?
Tiny telangiectatic vessels in the intestinal mucosa can leak or rupture, causing chronic blood loss, anemia, and sometimes life-threatening bleeding. Endoscopy and medical or surgical treatments aim to control these fragile vessels. -
What neurological problems are common?
Patients may develop seizures, spasticity, ataxia, headaches, cognitive changes, and sometimes signs of raised intracranial pressure, depending on where calcifications, white-matter changes, and cysts are located in the brain. -
How long do people with CRMCC live?
Published cases show very variable survival, from early childhood to adulthood, depending on the severity of brain, eye, gut, and marrow involvement. Intensive supportive care and newer therapies may improve outcomes, but the condition remains serious. -
Can children with CRMCC go to school?
Many children attend school with support such as low-vision aids, individualized education plans, and physical or speech therapy. The level of assistance needed depends on each child’s vision, mobility, and learning profile. -
Is pregnancy possible for someone with CRMCC?
Experience is extremely limited. Because of bone fragility, anemia, and potential organ involvement, pregnancy would be very high risk and would require preconception counseling and specialist high-risk obstetric care. -
Are brothers and sisters at risk?
In autosomal recessive families, each full sibling of an affected person has a 25% chance of being affected, a 50% chance of being a carrier, and a 25% chance of being unaffected and not a carrier. Genetic counseling clarifies exact risks. -
Can CRMCC be detected before birth?
If the family’s disease-causing variants are known, prenatal or preimplantation genetic diagnosis may be possible in future pregnancies, but this requires careful genetic and ethical counseling. -
What research is happening now?
Current research explores better imaging, natural-history studies, telomere biology, anti-VEGF therapies, and hematopoietic stem-cell transplant strategies, often shared through case reports, registries, and small trials for Coats plus and related disorders. -
Where can families find support?
Families can connect with rare-disease organizations, telomere-biology disorder groups, and condition-specific charities and networks that provide information, peer support, and help with accessing expert centers and research opportunities.
Disclaimer: Each person’s journey is unique, treatment plan, life style, food habit, hormonal condition, immune system, chronic disease condition, geological location, weather and previous medical history is also unique. So always seek the best advice from a qualified medical professional or health care provider before trying any treatments to ensure to find out the best plan for you. This guide is for general information and educational purposes only. Regular check-ups and awareness can help to manage and prevent complications associated with these diseases conditions. If you or someone are suffering from this disease condition bookmark this website or share with someone who might find it useful! Boost your knowledge and stay ahead in your health journey. We always try to ensure that the content is regularly updated to reflect the latest medical research and treatment options. Thank you for giving your valuable time to read the article.
The article is written by Team RxHarun and reviewed by the Rx Editorial Board Members
Last Updated: February 01, 2025.
