Crome syndrome is an extremely rare and very severe genetic syndrome that affects the eyes, brain, and kidneys of a newborn baby. It is also called cataract-nephropathy-encephalopathy syndrome. Babies with this condition are usually born with cloudy lenses in both eyes (congenital cataracts), have serious brain problems (encephalopathy) with seizures, and have severe kidney damage called renal tubular necrosis. Because of these combined problems, the condition is usually lethal in early infancy, and in the classic cases the babies died between 4 and 8 months of age. NCBI+3Wikipedia+3Genetic Rare Diseases Center+3
Crome syndrome (also called cataract-nephropathy-encephalopathy syndrome) is an ultra-rare genetic disease. It causes a combination of congenital cataracts, severe brain injury (encephalopathy), epileptic seizures, kidney damage (renal tubular necrosis), poor growth, and profound developmental delay. Only a few infants have ever been described in the medical literature, and most died in early infancy (around 4–8 months). EMBL-EBI+4PubMed+4Wikipedia+4
Because the condition is so rare and usually lethal, there is no cure and no standard treatment protocol. Care is “supportive” or “palliative”: doctors try to reduce suffering, treat seizures, support vision and kidney function, help with feeding and breathing, and support the family. braintherapeutics.gr+4Genetic Rare Diseases Center+4orpha.net+4
Doctors believe Crome syndrome is autosomal recessive, which means the baby receives one faulty gene from each parent. The syndrome has been reported in only two sisters of first-cousin parents, and there have been no clearly confirmed new cases in the medical literature since the original report in 1963. This shows how rare the condition is and how limited our scientific information remains. monarchinitiative.org+3malacards.org+3orpha.net+3
Because information is so scarce, almost everything we know comes from that original description and summaries collected in rare-disease databases such as Orphanet, GARD, MedGen, and Malacards. This also means that many details about genes, long-term outcomes, or exact mechanisms are still unknown, and doctors must often rely on general knowledge about similar genetic syndromes when they try to understand or explain Crome syndrome. DoveMed+4Genetic Rare Diseases Center+4malacards.org+4
Other names for Crome syndrome
Crome syndrome has several other names that describe its main features. The most common synonym is “cataract-nephropathy-encephalopathy syndrome.” This name reminds us that the syndrome always includes cataracts (cloudy eye lenses), nephropathy (kidney disease), and encephalopathy (serious brain dysfunction). Rare-disease resources such as Orphanet, GARD, Malacards, and MedGen all list this as an official synonym. NCBI+3Genetic Rare Diseases Center+3malacards.org+3
Another widely used term is “congenital cataract, nephropathy, encephalopathy syndrome.” The word “congenital” means that the cataracts are already present at birth. MedGen and GARD use this name interchangeably with Crome syndrome. It is helpful because it tells doctors that the problem starts very early in life and involves several organs at the same time. Genetic Rare Diseases Center+2NCBI+2
In some older texts and ontology systems, the condition is also described by its original clinical phrase “congenital cataracts, renal tubular necrosis and encephalopathy in two sisters.” This wording comes directly from the first report written in 1963, which described the two affected girls in a single family. Today this phrase is mainly used as a descriptive label in databases, but it still reflects the key features: cataracts, kidney failure, and severe brain disease. EMBL-EBI+3Wikipedia+3malacards.org+3
Types of Crome syndrome
Because only two infants with this condition have been clearly reported, most expert sources describe only one “classic” type of Crome syndrome. This classic type is a neonatal, lethal, multisystem syndrome with short stature, congenital cataracts, seizures, encephalopathy, and severe kidney tubular damage. There is no formal medical classification that recognizes separate mild or late-onset forms, so in strict evidence-based terms there is just one main form. DoveMed+3Genetic Rare Diseases Center+3malacards.org+3
Some authors talk in a more practical way about “suspected” Crome-like cases in babies who have congenital cataracts plus brain and kidney disease, but without full proof that they match the original report. These situations are usually grouped with Crome syndrome when doctors search for similar patterns, but they are not officially recognized as different types. It is important to understand that this is more a clinical convenience than a formal subclassification. Global Genes+1
Another useful concept is the “carrier state” in parents of an affected child. In an autosomal recessive condition, each parent is usually a healthy carrier, meaning they have one normal copy and one faulty copy of the same gene. Carriers usually do not have symptoms, but they can pass the mutation to their children. Rare-disease resources and genetics texts explain this general pattern for autosomal recessive diseases, and specialists assume that Crome syndrome follows the same pattern even though the exact gene has not yet been identified. Genetic Rare Diseases Center+2malacards.org+2
Causes of Crome syndrome
Because Crome syndrome is so rare, the exact gene and molecular cause are still unknown. However, doctors and geneticists can describe several key causes and mechanisms based on the family pattern and on what we know from similar conditions. The list below explains 20 related “cause components.” Many of them are different aspects of the same underlying genetic problem, not 20 completely separate diseases.
Autosomal recessive inheritance
The two original infants with Crome syndrome were sisters born to first-cousin parents, and genetic databases such as Orphanet and MedGen classify the condition as autosomal recessive. This means a child must receive one faulty gene from each parent to develop the disease, while each parent is usually healthy but carries a single copy of the mutation. malacards.org+2orpha.net+2Unknown single-gene mutation
Crome syndrome is thought to result from a change in a single gene, but the specific gene has not yet been discovered. GARD and Orphanet list it as a genetic disease caused by DNA changes, but acknowledge that no precise gene has been mapped. This uncertainty limits options for genetic testing and counseling. Genetic Rare Diseases Center+1Defective lens development (congenital cataracts)
The presence of dense cataracts at birth suggests a mutation affecting proteins that keep the eye lens clear. In general, congenital cataracts can result from mutations in crystallin proteins, membrane proteins, or enzymes that handle lens metabolism. While the exact pathway in Crome syndrome is unknown, the cataract component indicates abnormal lens development as part of the causal chain. Wikipedia+2malacards.org+2Kidney tubular injury and nephropathy
Autopsy findings in the original cases showed renal tubular necrosis, which is a form of severe damage to the tiny tubes that process urine in the kidney. This implies that the underlying mutation disrupts kidney cell survival or function, leading to nephropathy that plays a major role in the baby’s decline. NCBI+3Wikipedia+3Genetic Rare Diseases Center+3Brain injury and encephalopathy
The syndrome includes severe encephalopathy, seizures, and sometimes cerebellar dysplasia. This pattern suggests that the same genetic change interferes with brain development and brain cell metabolism, causing widespread dysfunction and early seizures in the newborn. DoveMed+3Wikipedia+3malacards.org+3Cerebellar maldevelopment
Malacards and other sources mention cerebellar dysplasia in Crome syndrome. The cerebellum helps control movement and balance. Abnormal formation of this structure is another sign that the disease process begins during fetal development and affects multiple parts of the central nervous system. malacards.org+1Genetic disruption of multisystem development
Because the eyes, kidneys, brain, and growth are all affected at the same time, many experts suspect that Crome syndrome involves a gene that plays a role in early embryonic development of several organs. This idea is based on the multi-organ pattern described in the original publication and summarized in rare-disease databases, even though the exact developmental pathway is still unknown. Wikipedia+2malacards.org+2Consanguinity as a risk factor for the mutation
The two affected infants were born to first-cousin parents. Consanguineous marriage increases the chance that both parents carry the same rare recessive mutation. This does not “cause” the mutation, but it increases the chance that a child will inherit two copies and develop the syndrome. malacards.org+2orpha.net+2Possible disturbance of cellular energy use
Many early-onset encephalopathy and kidney-cataract syndromes involve problems with mitochondria or cell energy pathways. Although this has not been directly proven in Crome syndrome, researchers consider impaired energy production a plausible mechanism that could link brain, lens, and kidney damage in a single genetic disorder. Genetic Rare Diseases Center+2malacards.org+2Abnormal protein processing in lens and kidney cells
Another possible mechanism is faulty processing or folding of key proteins in lens fibers and kidney tubular cells. In other congenital cataract and nephropathy syndromes, misfolded proteins can build up and damage cells. Because Crome syndrome shares similar clinical features, scientists consider this a reasonable, though still theoretical, cause pathway. malacards.org+2Global Genes+2Disruption of cell death (apoptosis)
Renal tubular necrosis and brain damage can arise when programmed cell death pathways are over-activated or poorly controlled. Many genetic syndromes cause excessive apoptosis in particular organs. Crome syndrome likely involves some such disturbance, given the severe tissue destruction seen in kidneys and brain at autopsy. Wikipedia+2NCBI+2Possible vascular or blood-flow problems in the kidney
In general kidney medicine, acute tubular necrosis can follow reduced blood flow or toxic injury. CheckOrphan and other summaries note renal tubular necrosis in Crome syndrome, and nephrology texts suggest that genetic defects can make tubular cells more vulnerable to even mild blood-flow changes. This vulnerability may be part of the causal picture. NCBI+2DoveMed+2Very early (prenatal) onset of disease processes
The presence of cataracts at birth and severe illness in the first months show that the damaging processes are already active during pregnancy. Rare-disease summaries emphasize neonatal onset, which means the cause is operating before birth, likely during critical windows of organ formation. Genetic Rare Diseases Center+2orpha.net+2Genetic instability or de novo mutation in some families
In some autosomal recessive diseases, the mutation may arise “de novo” in one parent’s germ cells. Although this has not been directly studied in Crome syndrome, this mechanism is generally recognized for many rare recessive syndromes and may explain how the mutation first appears in a family line. Genetic Rare Diseases Center+1Disturbed growth signaling pathways
Short stature is a core feature in the original cases. This suggests that whatever gene is involved may disturb signaling systems that control body growth, either directly (through growth plate development) or indirectly (through chronic illness and malnutrition caused by kidney and brain disease). malacards.org+2Global Genes+2Metabolic imbalance due to kidney failure
Severe kidney tubular damage leads to loss of salts, acids, and water control. These imbalances in turn worsen brain function and growth. Although this is more a consequence than a primary cause, it feeds back and becomes part of the overall disease mechanism in Crome syndrome. malacards.org+2DoveMed+2Seizure-related brain injury
Repeated or prolonged seizures can cause additional brain damage on top of the underlying genetic encephalopathy. Crome syndrome includes epileptic fits, and pediatric neurology literature shows that uncontrolled seizures in early life can worsen cognitive and motor outcomes, adding a secondary injury component to the primary genetic cause. Wikipedia+2malacards.org+2Possible modifier genes
In many rare genetic diseases, extra “modifier” genes change how severe the main condition becomes. For Crome syndrome, no modifiers have been identified, but researchers recognize this as a general principle that could explain differences if more cases are ever reported. malacards.org+2Global Genes+2Environmental stresses acting on an already fragile system
Factors such as infections, dehydration, or perinatal stress might not cause Crome syndrome by themselves, but they can worsen kidney or brain injury in a baby whose organs are already fragile because of the genetic defect. This idea is drawn from experience with other neonatal renal and encephalopathic syndromes. DoveMed+1Lack of specific gene identification as an ongoing cause of uncertainty
A final “cause” in a broader sense is that the missing gene discovery itself is a barrier. Without a known gene, families cannot have simple carrier or prenatal testing, and scientists cannot study the exact pathway. Rare-disease registries continue to list the disease with unknown molecular basis, which shows that this knowledge gap is an important part of why we still cannot fully explain Crome syndrome’s cause. NCBI+3Genetic Rare Diseases Center+3malacards.org+3
Symptoms of Crome syndrome
Again, almost all symptom information comes from the original two infants and a few summary resources. The list below combines documented features with logical consequences of those features in similar conditions. Where data are limited, this is noted.
Short stature and poor growth
The classic description of Crome syndrome includes short stature. Babies are small for their age and may not gain weight or length as expected, partly because of severe illness and feeding difficulties. malacards.org+2Global Genes+2Congenital cataracts
Both lenses are cloudy at birth, making it hard or impossible for the baby to see clearly. Congenital cataracts are a central sign of this syndrome and are present in nearly all reported summaries. DoveMed+3Wikipedia+3Genetic Rare Diseases Center+3Vision impairment or blindness
Because the cataracts are dense and appear very early, the baby’s ability to see is seriously reduced. If cataracts are not removed very quickly, the visual pathways in the brain cannot develop normally, leading to permanent visual disability or blindness. malacards.org+2DoveMed+2Nystagmus (shaking eye movements)
Some summaries list nystagmus as a frequent feature. The baby’s eyes may move rapidly or jerk from side to side. This often happens when vision is poor or when the brain regions controlling eye movements are affected. malacards.org+1Seizures (epileptic fits)
Epileptic seizures are one of the most important signs of Crome syndrome. They may occur as jerking movements, stiffening, or subtle repeated behaviors in the newborn. Seizures reflect underlying encephalopathy and are described consistently in rare-disease summaries. DoveMed+3Wikipedia+3Genetic Rare Diseases Center+3Encephalopathy (severe brain dysfunction)
Encephalopathy in Crome syndrome means that the baby’s brain is not working normally. This can cause poor alertness, weak suck, abnormal muscle tone, and delayed responses. In the original cases, the brain changes were so severe that the infants could not survive infancy. Wikipedia+2malacards.org+2Intellectual disability / developmental delay
Because of the severe early brain damage, surviving time is too short to formally test mental development, but databases describe intellectual disability as a key phenotype. If a child were to live longer, they would be expected to have profound developmental delay. malacards.org+2Global Genes+2Cerebellar dysplasia and coordination problems
In reported summaries, cerebellar dysplasia is noted, meaning the cerebellum is formed abnormally. This structure helps with posture and coordination, so its maldevelopment likely contributes to abnormal movements and poor motor skills in affected babies. malacards.org+1Renal tubular dysfunction
The kidneys cannot handle salts, acids, and water correctly because the renal tubules are badly damaged. This can lead to dehydration, acidosis, and abnormal levels of electrolytes in the blood, and is central to the “nephropathy” part of the syndrome. malacards.org+2NCBI+2Acute tubular necrosis and kidney failure
In the original cases, autopsy showed tubular necrosis, meaning many tubular cells were dead. This leads to severe kidney failure, reduced urine output, and buildup of toxins in the bloodstream, which worsens the baby’s condition and contributes to early death. CheckOrphan+3Wikipedia+3malacards.org+3Feeding difficulties and poor sucking
Babies with severe encephalopathy and seizures often have trouble sucking and swallowing. They may tire quickly during feeds, choke, or need feeding tubes. This is not unique to Crome syndrome but is a reasonable and likely symptom based on the reported brain involvement. DoveMed+1Failure to thrive
Poor feeding, recurrent illness, and kidney losses of nutrients lead to “failure to thrive,” meaning the baby does not gain weight or grow along normal growth curves. This symptom is common in many serious neonatal syndromes and fits with the short stature described in Crome syndrome. malacards.org+1Lethargy or reduced alertness
Encephalopathy and metabolic problems from kidney failure can make the baby very sleepy, floppy, or unresponsive. Caregivers may notice that the baby does not cry strongly, does not wake easily for feeds, and seems “too quiet” or “too weak.” Wikipedia+2malacards.org+2Breathing problems
Severe seizures, brain involvement, and acidosis from kidney failure can all affect breathing. Some infants may have irregular breathing, shallow breaths, or need ventilatory support. While not listed separately in every database, this is a logical complication in such a severe multisystem disorder. malacards.org+2DoveMed+2Very poor overall prognosis with early death
Almost all sources agree that Crome syndrome is a lethal condition in early infancy, with death usually between 4 and 8 months of age in the classic cases. This very poor prognosis is itself a “clinical feature” that doctors must discuss carefully with families when the diagnosis is considered. NCBI+3Wikipedia+3Genetic Rare Diseases Center+3
Diagnostic tests for Crome syndrome
Because Crome syndrome is so rare, diagnosis is usually clinical, meaning doctors recognize the pattern of eye, kidney, and brain problems in a very sick newborn. The following tests help to support the diagnosis, rule out other causes, and understand organ damage. In practice, many of these tests are used to evaluate any critically ill newborn with cataracts, seizures, and kidney problems, not only Crome syndrome.
Physical examination tests
Full newborn physical exam
The doctor carefully checks the baby’s size, weight, head circumference, vital signs, skin color, breathing, and general responsiveness. In Crome syndrome, the exam may show short stature, poor tone, abnormal movements, and general signs of severe illness. DoveMed+1Growth and anthropometric assessment
Measuring length, weight, and head size and plotting them on growth charts helps show short stature and poor growth. These measurements support the idea of a severe multisystem disorder when combined with other findings. malacards.org+2Global Genes+2Neurological examination
The doctor examines reflexes, muscle tone, spontaneous movements, and response to stimuli. Abnormal reflexes, weak or stiff muscles, and poor responsiveness indicate encephalopathy and brain dysfunction, which is a key part of Crome syndrome. Wikipedia+2malacards.org+2Ophthalmologic inspection at the bedside
Even before specialized equipment is used, shining a light into the baby’s eyes can show a white or gray reflex where a red reflex should be. This simple physical sign alerts doctors to congenital cataracts and prompts urgent eye-care referral. Wikipedia+2Genetic Rare Diseases Center+2Cardiorespiratory examination
Listening to the heart and lungs and checking for swelling or fluid helps detect complications of kidney failure, such as fluid overload or high blood pressure. These findings support the presence of severe systemic illness. malacards.org+2DoveMed+2
Manual and bedside tests
Slit-lamp eye examination
An eye specialist uses a slit-lamp microscope to look closely at the lens and other eye structures. In Crome syndrome this confirms dense bilateral congenital cataracts and helps rule out other eye malformations. Wikipedia+2malacards.org+2Indirect ophthalmoscopy
Using a special lens and light, the doctor examines the retina and optic nerve. This test checks whether the back of the eye is structurally normal and whether the cataract is the main cause of visual impairment. Wikipedia+1Bedside developmental assessment
Simple tests, such as observing eye contact, tracking, sucking, and response to sound, help estimate developmental level. In Crome syndrome, severe encephalopathy means these responses are usually very limited even early in life. malacards.org+1Manual neurological maneuvers
Tests such as the Moro reflex, grasp reflex, and tone assessment through passive limb movement are done manually at the bedside. Abnormal results point toward global brain involvement and guide decisions about further imaging and EEG. Wikipedia+1Blood pressure and fluid balance monitoring
Manual and automated checks of blood pressure, daily weights, and fluid input/output help detect kidney failure and its effects. High blood pressure, edema, or very low urine output in a newborn with cataracts and seizures strongly suggest a serious kidney problem such as that seen in Crome syndrome. malacards.org+2DoveMed+2
Laboratory and pathological tests
Basic blood tests (electrolytes, urea, creatinine)
These tests measure kidney function and the balance of salts and waste products. In Crome syndrome, results often show severe kidney failure, acidosis, and disturbed electrolytes, confirming nephropathy’s contribution to the illness. malacards.org+2NCBI+2Urinalysis and tubular function studies
Checking the urine for protein, glucose, and other substances helps detect tubular dysfunction, where the kidney tubules leak substances that should be reabsorbed. This fits with the tubular necrosis described in autopsy studies. malacards.org+2NCBI+2Blood gas analysis
Measuring blood pH and gases shows acidosis and other disturbances caused by kidney failure and poor breathing. In infants with Crome syndrome, this test provides critical information for intensive care, even though it does not by itself prove the specific diagnosis. DoveMed+1Metabolic and genetic screening panels
Doctors often send broader panels looking for other metabolic or genetic diseases that can cause cataracts, kidney problems, and encephalopathy. Even if no specific marker for Crome syndrome exists, negative results help rule out more common conditions and support the idea of a very rare, possibly novel syndrome. Genetic Rare Diseases Center+2orpha.net+2Renal biopsy or autopsy pathology
In the original Crome cases, kidney tissue examined after death showed renal tubular necrosis. Today, renal biopsy in a critically ill newborn would be considered only in selected cases, but when tissue is available it can confirm the pattern of tubular damage typical of the syndrome. CheckOrphan+3Wikipedia+3malacards.org+3
Electrodiagnostic tests
Electroencephalogram (EEG)
EEG records the electrical activity of the brain. In Crome syndrome it can show abnormal background patterns and seizure discharges, confirming the presence of epileptic encephalopathy and guiding seizure management. Wikipedia+2malacards.org+2Evoked potential studies (where available)
Tests such as visual or auditory evoked potentials measure how the brain responds to sight or sound. In a baby with cataracts and suspected brain dysfunction, these tests can help show whether signals are reaching the brain and how well the brain is processing them. malacards.org+1
Imaging tests
Brain ultrasound or MRI
Neuroimaging is used to look for structural abnormalities such as cerebellar dysplasia, cortical atrophy, or other malformations. Reports on Crome syndrome mention cerebellar dysplasia and encephalopathy, which would be supported by imaging changes. MRI gives the most detail but may be challenging in unstable newborns. malacards.org+2NCBI+2Renal ultrasound
Ultrasound of the kidneys checks their size, structure, and blood flow. While tubular necrosis may not always show specific ultrasound changes, this test helps rule out other causes of kidney failure, such as structural malformations or obstruction. malacards.org+2DoveMed+2Echocardiography and chest imaging
Heart ultrasound and chest X-rays are sometimes done to assess overall health, fluid status, and the effects of kidney failure and severe illness on the heart and lungs. Although not specific for Crome syndrome, these studies are part of the full evaluation of a critically ill newborn with this kind of multisystem disease. DoveMed+1
Non-Pharmacological Treatments (Therapies and Other Supportive Measures)
1. Multidisciplinary care coordination
A central non-drug treatment for Crome syndrome is close coordination between several specialists: neonatology, pediatric neurology, nephrology, ophthalmology, physiotherapy, nutrition, and palliative-care teams. Regular case meetings help everyone share information, prioritize comfort, and choose realistic goals such as seizure control, feeding safety, and family support, rather than cure. Research in rare lethal syndromes shows that multidisciplinary clinics improve communication and reduce fragmented care for families. DoveMed+2malacards.org+2
2. Early visual assessment and cataract management planning
Infants with Crome syndrome have congenital cataracts, which can severely block light from reaching the retina. In other conditions, early cataract surgery within weeks or months can protect visual development. nhs.uk+4Medscape+4EyeWiki+4 However, in Crome syndrome, doctors must balance potential visual benefit against anesthesia risk, severe brain injury, and short life expectancy. A pediatric ophthalmology team assesses the infant’s visual potential, general condition, and family wishes, and may recommend surgery, optical aids, or purely comfort-focused care.
3. Low-vision and sensory stimulation programs
Even if perfect vision cannot be achieved, low-vision strategies can help the baby respond to the environment. Simple high-contrast toys, gentle sound and touch, and consistent positioning help stimulate remaining senses. Studies in children with severe brain and visual impairment show that multisensory stimulation may slightly improve alertness and interaction, even when structural damage is profound. EyeWiki+1
4. Seizure first-aid training for parents and caregivers
Crome syndrome often includes recurrent epileptic seizures. Families are taught simple, evidence-based seizure first aid: keeping the baby on the side, protecting the head, not putting anything in the mouth, and noting seizure duration to report to doctors. Guidelines for pediatric epilepsy stress caregiver education as a key part of safe home care and early emergency response. Epilepsy12 Platform+2DoveMed+2
5. Physiotherapy for posture and contracture prevention
Because of hypotonia, encephalopathy, and limited movement, babies with Crome syndrome are at risk of joint stiffness, contractures, and pressure sores. Gentle physiotherapy, frequent position changes, and soft splints can help maintain comfortable posture. Evidence from other severe neurodevelopmental conditions suggests that early positioning programs reduce pain and skin breakdown and make daily care easier for caregivers. Nature+1
6. Occupational therapy and feeding strategies
Feeding is often difficult due to poor suck, swallowing problems, and risk of aspiration. Occupational therapists and speech-and-swallow specialists can assess feeding safety and recommend techniques such as upright positioning, thickened feeds, or tube feeding when needed. In infants with brain injury, early swallow assessment is recommended to prevent recurrent pneumonia and to ensure adequate nutrition. Nature+1
7. Nutritional support and growth monitoring
Failure to thrive is common in Crome syndrome because of feeding problems, kidney disease, and high metabolic stress. Dietitians design high-calorie, easily digestible feeding plans by breast milk, formula, or tube feeding. Regular weight and length checks guide adjustments. Evidence from other rare infant syndromes shows that individualized nutrition improves energy levels, wound healing, and overall comfort, even when long-term survival is limited. orpha.net+2Nature+2
8. Fluid and electrolyte management without drugs where possible
Renal tubular necrosis and nephropathy can cause major fluid and electrolyte imbalances. Careful control of fluid intake (how much milk, formula, or tube feed is given) and monitoring of urine output can sometimes reduce the need for aggressive drug therapy. Pediatric kidney guidelines emphasize individualized fluid plans and close monitoring to prevent both dehydration and fluid overload. PubMed+2PMC+2
9. Respiratory and airway support
Some infants may need oxygen, careful suctioning of secretions, or non-invasive ventilation for comfort. The goal is usually to ease breathing effort rather than to prolong life at all costs. Evidence from palliative care in severe neurologic disease shows that simple measures like positioning, nasal saline, and low-flow oxygen can significantly improve comfort and reduce distress. braintherapeutics.gr+1
10. Pain and comfort assessment using non-drug methods
Babies cannot speak, so nurses use validated neonatal pain scales that look at facial expressions, heart rate, and body movements. Non-drug comfort measures such as swaddling, skin-to-skin contact, gentle rocking, and minimizing invasive procedures are prioritized. Neonatal guidelines recommend combining environmental comfort with medications when needed to keep the baby calm and pain-free. braintherapeutics.gr+1
11. Psychological and social support for the family
Crome syndrome is devastating for parents. Psychologists, social workers, and spiritual-care providers offer counseling, help families process grief, and assist with practical issues such as financial support and home nursing. Research in families of children with lethal genetic disorders shows that early psychological support reduces complicated grief and improves long-term mental health. braintherapeutics.gr+1
12. Palliative and end-of-life care planning
Because Crome syndrome is usually lethal in infancy, early discussion of goals of care is essential. Palliative care teams help families make decisions about resuscitation, intensive care, and preferred place of care (hospital or home). International rare-disease and palliative-care guidelines emphasize honest communication, symptom control, and respect for family values to preserve dignity at the end of life. orpha.net+2DoveMed+2
(In practice, clinicians will adapt and combine these approaches rather than using a rigid list.)
Drug Treatments
Important: No medicine is approved specifically to cure Crome syndrome. The drugs below are used worldwide for related problems such as seizures or kidney failure, and their use in this syndrome is off-label and highly individualized. Exact doses are weight-based and must be set by the treating team.
1. Levetiracetam (e.g., KEPPRA, SPRITAM) – antiepileptic
Levetiracetam is a broad-spectrum seizure medicine widely used in infants and children with epilepsy. It is approved by the FDA for various seizure types and has intravenous and oral forms. FDA Access Data+4FDA Access Data+4FDA Access Data+4 In Crome syndrome, levetiracetam may be chosen because it has relatively few drug–drug interactions and can be adjusted in kidney disease. Doctors usually start with a low, weight-based dose, then slowly increase while monitoring seizure control, drowsiness, irritability, or behavioral changes.
2. Phenobarbital (e.g., SEZABY; phenobarbital tablets) – antiepileptic, neonatal first-line
Phenobarbital has long been used as a first-line treatment for neonatal seizures and remains a standard option. FDA Access Data+4FDA Access Data+4FDA Access Data+4 It works by enhancing GABA-mediated inhibition in the brain. In Crome syndrome, specialists may use it early to control frequent seizures, especially in the neonatal intensive-care setting. Side effects include excessive sleepiness, breathing depression, low blood pressure, and long-term effects on development, so clinicians balance seizure control against these risks and monitor carefully.
3. Other antiepileptic drugs (AEDs) as needed
If seizures remain uncontrolled, doctors may add or switch to other FDA-approved AEDs such as valproate, lamotrigine, or newer agents, depending on seizure type and organ function. FDA Access Data+3FDA Access Data+3FDA Access Data+3 Evidence from pediatric epilepsy shows that combined therapy may be needed, but polypharmacy increases side effects. In Crome syndrome, the team often aims for “good enough” seizure reduction (to avoid distress) rather than complete seizure freedom if side effects are severe.
4. Furosemide – loop diuretic for fluid overload
Furosemide is a powerful diuretic used to remove excess fluid in many kidney and heart conditions. FDA labeling warns that high doses can cause dehydration and electrolyte loss, so careful supervision is required. FDA Access Data+4FDA Access Data+4FDA Access Data+4 In Crome syndrome with renal tubular necrosis, furosemide may be used to manage edema or high blood pressure. Doctors adjust the dose based on urine output, blood tests, and blood pressure, watching for low potassium, low sodium, or hearing problems (ototoxicity).
5. Bicarbonate and electrolyte replacement solutions
Acid–base and electrolyte disturbances are common in advanced kidney disease. Intravenous or oral sodium bicarbonate and tailored electrolyte solutions (e.g., for sodium, potassium, calcium) are used to correct these imbalances. Pediatric nephrology guidelines support bicarbonate therapy to improve metabolic acidosis and growth in chronic kidney disease, but in Crome syndrome, the goal is mainly comfort and prevention of acute crisis. PubMed+2PMC+2
6. Antihypertensive medicines (e.g., ACE inhibitors, beta-blockers)
If kidney damage leads to high blood pressure, doctors may introduce blood-pressure medications such as ACE inhibitors or beta-blockers. These are widely used and FDA-approved for pediatric hypertension in other settings. They lower pressure to protect the heart and brain and reduce symptoms like irritability and headache in older children; in infants, they mainly prevent acute hypertensive crises. Renal function and potassium levels must be monitored closely. PubMed+2monarchinitiative.org+2
7. Antibiotics for infections
Infants with Crome syndrome are fragile and prone to infections such as pneumonia or urinary tract infections. Clinicians use standard, FDA-approved antibiotics guided by culture results and local protocols. The choice depends on likely organisms and kidney function. Evidence in neonates shows that early, appropriate antibiotics reduce sepsis-related mortality, but overuse can cause resistance and side effects, so treatment is targeted and time-limited whenever possible. braintherapeutics.gr+1
8. Analgesics and sedatives for pain and agitation
Medicines such as acetaminophen and carefully dosed opioids (like morphine) may be used to relieve pain from procedures, spasms, or severe discomfort. Neonatal palliative-care guidelines support the use of opioids and sedatives when non-drug measures are not enough. Side effects include drowsiness, constipation, and respiratory depression, so they must be titrated slowly and re-evaluated frequently. braintherapeutics.gr+1
9. Antiemetics and reflux medicines
Gastroesophageal reflux and vomiting are common in neurologically impaired infants. Doctors may prescribe proton-pump inhibitors or H2 blockers to reduce stomach acid and antiemetics to decrease vomiting episodes. Evidence from pediatric gastroenterology suggests these drugs can reduce esophagitis and discomfort, but they do not cure the underlying neurologic cause of reflux. Nature+1
10. Dialysis-related medications in advanced renal failure
If the medical team and family decide to initiate dialysis, the infant may receive medications commonly used in pediatric dialysis programs, such as vitamin D analogs, phosphate binders, or drugs to treat anemia (erythropoiesis-stimulating agents). These therapies are evidence-based in chronic kidney disease and dialysis populations, but in Crome syndrome decisions are highly individualized and sometimes dialysis is not pursued because the prognosis is extremely poor. PubMed+2PMC+2
Dietary Molecular Supplements
Note: No supplement has been proven to treat or cure Crome syndrome. Supplements are considered only to support general health, and must be supervised by the medical team, especially when kidney function is poor.
1. Energy-dense infant formula
High-calorie formulas provide more energy in a smaller volume, which is useful when babies cannot tolerate large feeds. In infants with severe neurologic disease, energy-dense formulas have been shown to improve weight gain and reduce hospitalizations for malnutrition. The dosage (number of feeds per day, volume per feed) is decided by the dietitian and pediatrician based on weight, growth rate, and kidney status. Nature+1
2. Medium-chain triglyceride (MCT)–enriched formula
MCT fats are easier to absorb and can be helpful if there is fat-malabsorption or poor digestion. They provide quick energy and may be used in specialized formulas or added as oils. Evidence from other pediatric disorders shows that MCT formulas can improve weight gain, but they must be balanced with essential fatty acids from other sources. Nature+1
3. Vitamin D supplementation
Children with kidney disease and limited sun exposure are at risk of low vitamin D and poor bone mineralization. Careful vitamin D supplementation, at doses suitable for infants and adjusted for kidney function, may help maintain bone health and reduce fracture risk. Pediatric nephrology guidelines recommend monitoring calcium, phosphorus, and parathyroid hormone when giving vitamin D in chronic kidney disease. PubMed+1
4. Calcium and phosphate balance support
In advanced nephropathy, disturbances of calcium and phosphate are common. Dietary phosphate restriction, combined with phosphate binders and calcium supplementation when appropriate, is a standard part of chronic kidney disease management. In Crome syndrome, this approach may be used if dialysis is started or if the baby survives long enough for mineral bone disease to become clinically relevant. PubMed+2monarchinitiative.org+2
5. Specialized electrolyte solutions for oral rehydration
When mild dehydration or vomiting occurs, oral rehydration solutions with balanced electrolytes can be safer than plain water. These solutions are designed based on WHO and pediatric guidelines to correct dehydration without causing dangerous sodium shifts. In Crome syndrome, the nephrology team will select or adjust a formula appropriate for kidney function. PubMed+1
6. Omega-3 fatty acid supplements (with caution)
Omega-3 fatty acids have general anti-inflammatory and cardiovascular benefits in many populations. While there is no evidence specific to Crome syndrome, clinicians sometimes consider small, carefully supervised doses as part of a balanced feeding plan. However, in very sick infants the priority is usually basic calories and protein rather than optional supplements, and any oil supplement must be discussed with the care team to avoid aspiration risk. braintherapeutics.gr+1
Immunity-Boosting” and Regenerative or Stem-Cell Drugs
There are no approved stem-cell or regenerative drugs for Crome syndrome, and no evidence that “immunity boosters” can change the course of this genetic, lethal disease. braintherapeutics.gr+3orpha.net+3DoveMed+3
Researchers are exploring stem-cell and gene-based therapies for some inherited kidney and neurologic disorders, but these are in early experimental stages and not available as routine clinical treatments. For infants with Crome syndrome, enrolling in such trials is currently unrealistic due to extreme rarity, medical fragility, and rapid disease progression. Families should be cautious of unregulated clinics offering “stem-cell cures” without scientific evidence.
When doctors talk about “supporting immunity” in Crome syndrome, they usually mean basic evidence-based steps: ensuring good nutrition, preventing and treating infections early, following standard vaccination schedules where feasible, and avoiding unnecessary invasive procedures. braintherapeutics.gr+1
Surgical Procedures and Why They May Be Done
1. Cataract surgery
In more common congenital cataract conditions, early surgery (within the first weeks or months of life) is recommended to prevent severe visual deprivation. Nature+4Medscape+4EyeWiki+4 Surgery removes the cloudy lens through a small incision, sometimes with later placement of an intraocular lens. In Crome syndrome, the team must consider whether the child’s overall prognosis and brain function justify the risk and postoperative demands. The main purpose is to give a chance for some light perception and interaction, not to cure the systemic disease.
2. Feeding tube placement (gastrostomy) in selected cases
If a child survives beyond early infancy but cannot safely swallow enough nutrition, surgeons may place a gastrostomy tube (G-tube) directly into the stomach. This procedure is common in children with severe neurologic impairment and has been shown to improve weight gain and reduce aspiration pneumonia in other disorders. Its role in Crome syndrome is theoretical and would only be considered if the child’s prognosis and family goals support longer-term supportive care. Nature+1
3. Dialysis catheter insertion
In rare situations where the team and family decide to attempt kidney replacement therapy, a catheter must be surgically placed for peritoneal dialysis or hemodialysis. Pediatric nephrology literature supports dialysis for children with severe renal failure, but in lethal syndromes decisions are complex and deeply personal. The purpose is to manage fluid overload and toxins, not to cure Crome syndrome. PubMed+2PMC+2
4. Central venous lines and other access procedures
Some infants need central venous lines for long-term medications or nutrition. These procedures are done under anesthesia and carry risks such as infection and thrombosis. In palliative situations, the team weighs these risks against the benefits of fewer needle sticks and more reliable access. braintherapeutics.gr+1
5. Palliative surgical or procedural interventions
Occasionally, simple procedures such as release of tight tendons or drainage of persistent fluid collections may be considered to reduce pain or pressure. These are not disease-modifying but can improve comfort in selected cases. Decisions are individualized and guided by palliative-care principles, not aggressive cure-oriented surgery. braintherapeutics.gr+1
Prevention and Risk Reduction
Because Crome syndrome is a genetic and extremely rare condition, it cannot be fully “prevented” by lifestyle changes. However, several steps can reduce the risk of recurrence or help with early detection and planning:
Genetic counseling for parents – Families who have had one affected child should be offered genetic counseling and, where possible, genetic testing (for example, genes such as SLC4A11 identified in related cataract-nephropathy-encephalopathy syndromes). orpha.net+2NCBI+2
Discussion of reproductive options – Counseling may include options like prenatal diagnosis or pre-implantation genetic testing in future pregnancies, when the causal mutation is known.
Early pregnancy and newborn screening – In at-risk families, targeted ultrasounds and early eye exams can help detect cataracts and other warning signs soon after birth. Nature+3Medscape+3EyeWiki+3
Avoidance of unproven “cures” – Families should be warned about unregulated stem-cell treatments or supplements marketed as cures for genetic disorders, since these can cause harm and financial stress without benefit. braintherapeutics.gr
Strict infection control in hospital – Good hand hygiene, vaccination of staff, and careful line care reduce secondary infections in fragile infants.
Safe feeding practices – Early swallow assessments and appropriate feeding methods can reduce aspiration and pneumonia risk. Nature+1
Careful medication choice and dose monitoring – Because kidneys are damaged, many drugs must be dose-adjusted or avoided to prevent further injury. FDA labels emphasize dose adjustments for drugs like levetiracetam and furosemide in renal impairment. FDA Access Data+2FDA Access Data+2
Family education on seizure safety – Teaching parents to recognize prolonged seizures and when to seek emergency help can prevent additional brain injury in other conditions, and is reasonable in Crome syndrome as well. Epilepsy12 Platform+1
Coordination with primary-care and community services – Early linkage to home nursing, hospice, and social services can prevent gaps in care and reduce crisis admissions. braintherapeutics.gr+1
Emotional and practical support for parents – Supporting parental mental health reduces burnout and improves their ability to participate in care decisions, which indirectly improves the infant’s experience and care quality. braintherapeutics.gr+1
When to See Doctors
Parents or caregivers of a baby with suspected or confirmed Crome syndrome should seek medical help:
Immediately (emergency): if the baby has a long seizure (lasting more than 5 minutes), repeated seizures without full recovery, severe difficulty breathing, very poor feeding with no wet diapers, unusual extreme sleepiness, blue lips or skin, or sudden swelling. These signs can indicate life-threatening complications such as status epilepticus, severe infection, or kidney failure. Epilepsy12 Platform+2PubMed+2
Urgently (same day): if there is fever, new cough, vomiting, diarrhea, reduced urine output, new eye redness or swelling, or sudden change in alertness.
Routinely: for planned follow-ups with pediatric neurology, nephrology, ophthalmology, nutrition, and palliative-care or hospice teams. Such regular visits allow slow adjustment of medicines, feeding plans, and comfort measures as the disease progresses. DoveMed+2malacards.org+2
Any family caring for a child with a condition as severe as Crome syndrome should have clear written instructions and phone numbers for their care team so that they know exactly whom to call in different situations.
What to Eat and What to Avoid
Because Crome syndrome affects very young infants, “diet” usually means breast milk, infant formula, or tube feeds, not adult foods. All decisions must be made by the medical and nutrition team, especially when kidney disease is advanced.
What the team usually encourages (when safe):
Breast milk where possible, for immune and nutritional benefits, often given by bottle or tube if direct breastfeeding is not safe.
High-calorie, nutrient-dense formulas to support growth when intake volume is limited. Nature+1
Balanced fluids matched to kidney function, avoiding both dehydration and overload.
Micronutrients such as vitamin D, iron, and trace elements when indicated by blood tests and kidney status. PubMed+1
Slow, frequent feeds that the baby can tolerate, to reduce reflux and vomiting. Nature+1
What the team usually avoids or restricts:
Excess free water (plain water) that can dilute sodium and worsen electrolyte problems.
High-salt preparations that can raise blood pressure and worsen fluid overload in kidney disease. PubMed+1
Unregulated herbal supplements or commercial “immunity boosters” without proven safety in infants or in kidney failure. braintherapeutics.gr
Large, fast feeds that increase reflux, aspiration risk, and distress.
Any supplement or food that conflicts with dialysis or mineral management, such as very high-phosphate foods, if the child reaches that stage and the nephrology team sets such limits.
For older siblings or family members who may be carriers but are otherwise healthy, a normal, balanced diet is recommended; no special “preventive diet” has been shown to influence the genetics of Crome syndrome. orpha.net+1
Frequently Asked Questions (FAQs)
1. Is Crome syndrome the same as cataract-glaucoma syndrome?
Crome syndrome is better known as cataract-nephropathy-encephalopathy syndrome, with cataracts, kidney disease, and severe brain involvement. EMBL-EBI+4orpha.net+4NCBI+4 Cataract-glaucoma syndrome generally refers to cataracts followed by glaucoma without the severe kidney and brain features. Some older sources loosely group these conditions, but modern classifications keep them separate.
2. What causes Crome syndrome?
Available genetic data suggest that Crome syndrome is a hereditary disorder caused by mutations in genes involved in eye and kidney development (similar conditions involve SLC4A11 and related pathways). orpha.net+2monarchinitiative.org+2 The exact gene for the original two reported sisters was not known in 1963, and very few cases have been described since.
3. How common is Crome syndrome?
Crome syndrome is extremely rare. Rare-disease databases estimate that fewer than 1,000 people in the United States have cataract-nephropathy-encephalopathy syndromes, and the specific Crome phenotype has been reported in only a handful of infants worldwide. EMBL-EBI+4Genetic Rare Diseases Center+4orpha.net+4
4. What are the main symptoms?
Typical features include congenital cataracts, epileptic seizures, severe developmental delay or intellectual disability, small stature, renal tubular necrosis, and encephalopathy. SpringerLink+4PubMed+4Wikipedia+4
5. Can Crome syndrome be cured with surgery or medicine?
No. At present there is no cure. Treatments can manage symptoms—such as seizures, cataracts, or fluid overload—but cannot reverse the underlying genetic brain and kidney damage. DoveMed+2malacards.org+2
6. Does cataract surgery fix the vision problem?
Cataract surgery can allow light into the eye and may improve visual responses, but vision may still be very limited because of severe brain damage and other eye problems. Outcomes depend on how early surgery is done and how damaged the visual pathways are. Nature+4Medscape+4EyeWiki+4
7. Can dialysis or kidney transplant cure the kidney part?
Dialysis can temporarily replace some kidney functions and relieve symptoms, but it is a demanding treatment and does not cure the brain or eye problems. Kidney transplant is not realistically considered in Crome syndrome because of the severe neurologic impairment and limited life expectancy. PubMed+2PMC+2
8. Are there gene therapies or stem-cell treatments available now?
No specific gene or stem-cell therapy is available for Crome syndrome. Research into gene therapy and stem-cell approaches for other kidney and neurologic diseases is ongoing, but these are experimental and not yet suitable for routine clinical use in such a fragile condition. braintherapeutics.gr+1
9. What is the usual prognosis?
Published reports describe infants with Crome syndrome dying in early infancy, often between 4 and 8 months of age, despite supportive care. malacards.org+4PubMed+4Wikipedia+4 Prognosis remains poor, although exact outcomes may vary by individual case.
10. Can future pregnancies be tested?
If the disease-causing mutation is identified in an affected child or the parents, prenatal or pre-implantation genetic testing may be possible in future pregnancies. Families should see a genetic counselor to discuss the available tests and their limitations. orpha.net+2NCBI+2
11. Is Crome syndrome inherited in a specific pattern?
The original cases suggested an autosomal recessive pattern, meaning both parents might carry one faulty copy of the gene. PubMed+2SpringerLink+2 Modern genetic testing can clarify the pattern in each family.
12. How can parents support their baby day-to-day?
Parents can focus on comfort: gentle touch, skin-to-skin contact, soft voices, and watching for signs of pain or distress. Working closely with the care team, maintaining feeding routines, and using recommended positioning aids make daily care safer and more comfortable. braintherapeutics.gr+1
13. Will my child feel pain?
Babies with Crome syndrome can feel pain, but the team uses validated neonatal pain scales and both non-drug and drug approaches to keep them comfortable. Palliative-care guidelines emphasize that good symptom control is a central goal in lethal pediatric conditions. braintherapeutics.gr+1
14. Can families choose home-based palliative care or hospice?
Yes. In many countries, home-based pediatric palliative-care or hospice services are available. Evidence suggests that families often appreciate the chance to spend more time at home with specialized support, though availability varies by region. braintherapeutics.gr+1
15. Where can families find more information and support?
Families can contact national and international rare-disease organizations, such as GARD, Orphanet, and Global Genes, which provide information and links to patient communities for cataract-nephropathy-encephalopathy syndrome and related conditions. Eurofins Biomnis Connect+4Genetic Rare Diseases Center+4orpha.net+4
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The article is written by Team RxHarun and reviewed by the Rx Editorial Board Members
Last Updated: November 16, 2025.
