Neuroectodermal dysplasia, CHIME type, is another name for CHIME syndrome. This is a very rare disease that affects many parts of the body, especially the skin, eyes, brain, ears, and heart. Doctors call it “neuroectodermal” because the problem starts in cells in the early embryo that later form the nervous system (brain, eyes, ears) and the outer layer of the body (skin). In CHIME syndrome, these cells do not develop in the normal way, so the child is born with several problems together: eye defects called colobomas, heart defects, a special kind of scaly red skin rash (ichthyosiform dermatosis), learning and developmental problems, and ear or hearing problems. NCBI+1
Neuroectodermal dysplasia, CHIME type, is another name for CHIME syndrome, a very rare genetic condition. The word “CHIME” comes from its main features: Coloboma of the eye, Heart defects, Ichthyosiform (dry, scaly) skin changes, Mental or intellectual disability, and Ear anomalies or epilepsy. It is also called Zunich–Kaye syndrome, neuroectodermal syndrome Zunich type, and congenital disorder of glycosylation due to PIGL deficiency (PIGL-CDG).Global Genes+3GARD Information Center+3Orpha+3
CHIME syndrome is inherited in an autosomal recessive pattern. That means a child usually needs to receive one changed (mutated) copy of the PIGL gene from each parent to have the condition. Parents are usually healthy carriers with one normal gene copy and one changed copy. CHIME syndrome affects the skin, brain, eyes, ears, heart, and sometimes kidneys and bones. It is extremely rare, with only a small number of cases reported worldwide.Orpha+2AccessPediatrics+2
Because CHIME syndrome is so rare, there is no single standard treatment and no cure. Care focuses on controlling seizures, protecting the heart and eyes, caring for the skin, supporting learning and hearing, and preventing infections. Children usually need lifelong follow-up with a team including pediatricians, neurologists, cardiologists, dermatologists, ophthalmologists, ENT doctors, therapists, and genetic counselors.Orpha+2AccessPediatrics+2
CHIME syndrome is genetic. It is usually caused by harmful changes (mutations) in a gene called PIGL. This gene helps make a fat–sugar structure called a GPI anchor. GPI anchors act like tiny “hooks” that hold some proteins on the outside of the cell. When PIGL does not work well, these hooks are made in the wrong way, so many proteins cannot attach properly. This leads to problems in many organs at the same time. Because of this, CHIME is also grouped as a congenital disorder of glycosylation. PubMed+1
CHIME syndrome is autosomal recessive. This means a child gets one faulty copy of the PIGL gene from each parent. The parents usually do not have the disease themselves, because they each carry only one faulty copy and one normal copy. The disease usually starts at birth or in early childhood and often lasts for life, but the exact severity can be different from person to person. Orpha+1
Other names
Neuroectodermal dysplasia, CHIME type, has many other names in the medical literature. These names describe the same condition but use different words: GARD Information Center+2Orpha+2
CHIME syndrome
Zunich–Kaye syndrome
Zunich neuroectodermal syndrome
Neuroectodermal syndrome, Zunich type
Congenital disorder of glycosylation due to PIGL deficiency
PIGL-CDG
Coloboma–congenital heart disease–ichthyosiform dermatosis–intellectual disability–ear anomalies syndrome
Coloboma, congenital heart disease, ichthyosiform dermatosis, mental retardation, and ear anomalies syndrome
All of these names point to the same core feature set: problems with eyes, heart, skin, brain function, and ear structure or hearing, caused by PIGL-related glycosylation defects.
Types
Doctors do not have a strict official list of “types” of neuroectodermal dysplasia, CHIME type. However, when they look at reported patients, they can see some patterns. For easy understanding, we can think about three broad clinical patterns or “forms.” These are only teaching groups, not formal scientific subtypes. DermaCompass+2Wiley Online Library+2
Classic CHIME form
In this pattern, the child shows almost all of the “CHIME” features: clear eye colobomas, heart defects, marked migratory scaly red skin rash from early life, moderate to severe learning problems, and typical ear anomalies with hearing loss. Seizures may also appear. This is the form described in most early case reports and reviews.
Mild or attenuated PIGL-related form
Some children with PIGL mutations have a milder picture. They may have the skin rash and learning problems but smaller or no visible heart defects, or very mild eye changes. In these cases, development may be better than in the classic form, and some features may only be seen on careful testing. Recent case reports describe such mild PIGL-related CHIME phenotypes. Wiley Online Library
Severe early-onset form
A few patients have very severe disease. They may have major heart defects, severe seizures, very marked ichthyosiform skin disease that is hard to treat, and significant feeding and growth problems very early in life. They often need intensive medical care and many hospital stays. Some recent reports describe severe skin disease in CHIME that required strong medicines. Wiley Online Library+1
Causes
1. PIGL gene mutations
The main cause of neuroectodermal dysplasia, CHIME type, is a harmful change in the PIGL gene. This change stops the gene from making a fully working PIGL enzyme. Without this enzyme, the normal GPI anchor pathway is disrupted, which affects many proteins on the cell surface. PubMed+1
2. Biallelic (two-copy) gene changes
The disease appears when both copies of the PIGL gene in the child’s cells are changed (mutated). One faulty copy comes from each parent. If only one copy is changed, the person is usually healthy and just a “carrier.” Orpha+1
3. Autosomal recessive inheritance
CHIME is inherited in an autosomal recessive way. The PIGL gene lies on one of the non–sex chromosomes. A child must receive one faulty gene from each parent to be affected. This explains why the disease can show up suddenly in a family where parents appear healthy. Orpha+1
4. Consanguinity (parents related by blood)
In some reported families, the parents are related (for example, cousins). When parents share ancestors, they have a higher chance of carrying the same rare gene mutation. This increases the risk that their child will inherit two faulty copies of PIGL and develop CHIME syndrome. Springer+1
5. GPI-anchor biosynthesis defect
PIGL is part of the pathway that makes GPI anchors. These anchors attach certain proteins to the outer cell membrane. When this pathway is broken, proteins that need GPI anchors cannot reach or stay on the cell surface. This leads to many organ problems at once. PubMed+1
6. Abnormal cell-surface protein display
Because GPI anchors do not form properly, many cell-surface proteins are missing or reduced. These proteins are important for cell signaling, adhesion, and protection. Their loss affects skin barrier, nerve development, heart formation, and hearing structures.
7. Disrupted neuroectoderm development
Neuroectoderm is the early tissue that forms skin, brain, eyes, and ears. In CHIME syndrome, defective GPI anchors in these cells lead to errors in growth and patterning. This explains why eye colobomas, ear anomalies, and brain-related problems occur together. Orpha+1
8. Abnormal brain and cognitive development
Because many brain cells need GPI-anchored proteins for normal communication, PIGL defects can disturb brain wiring. This can lead to developmental delay, intellectual disability, and seizures. NCBI+1
9. Abnormal eye development (coloboma)
Eye coloboma happens when a gap in the eye structure does not close in the embryo. In CHIME, faulty cell signaling from the glycosylation defect can disturb this closing step, causing colobomas of the iris, retina, or optic nerve. Orpha+1
10. Abnormal skin barrier formation
The skin rash in CHIME is called migratory ichthyosiform dermatosis. Abnormal GPI anchors change the behavior of skin cells and the lipids in the outer skin layer. This leads to dry, thick, scaly patches that move from one area to another. Wiley Online Library+1
11. Abnormal heart development
During early pregnancy, the heart is forming chambers and valves. In CHIME, the same glycosylation problem that affects skin and brain also affects heart cells. This can cause congenital heart defects such as holes between chambers or valve problems. MalaCards+1
12. Abnormal ear and hearing structure development
The outer and middle ear need precise tissue growth. When the PIGL pathway is abnormal, the ear shape can be unusual, and the ear canal and middle ear bones may not form correctly. Combined with skin build-up in the ear canal, this causes conductive hearing loss. Orpha+1
13. Abnormal craniofacial (face and skull) formation
Children with CHIME often have a broad, flat nasal bridge, wide-set eyes, and a flat midface. These come from early disturbances in head and face bone development linked to the neuroectodermal defect. Orpha+1
14. Genitourinary development problems
Some patients have kidney or urinary tract anomalies, such as hydronephrosis or a bicornuate uterus. These problems likely arise because GPI-anchored proteins are also important in the development of these organs. Springer+1
15. De novo mutations
In some families, one or both PIGL mutations may be de novo, meaning they appear for the first time in the child and were not present in previous generations. The inheritance pattern is still recessive, but the mutation itself is new in the family line.
16. Modifier genes
Other genes may modify how severe CHIME becomes. Two children with similar PIGL mutations can look very different. This suggests that additional genes and pathways can make the disease milder or more severe. This is a proposed explanation from case series, not fully proven. SciELO+1
17. Environment acting on a vulnerable embryo
There is no strong evidence that specific environmental factors cause CHIME. However, if the embryo already carries PIGL mutations, harmful exposures (such as severe infections or toxins in early pregnancy) might worsen organ development. This idea is theoretical and not well studied.
18. Immune and inflammatory effects
Abnormal skin barrier and glycosylation can change the immune response. Children may have more skin infections or inflammation, which can worsen the skin disease and overall health. Wiley Online Library+1
19. Nutritional and growth factors
Feeding difficulties and chronic illness can lead to poor nutrition and growth. While this does not cause CHIME, it can cause extra growth delay on top of the genetic disease, making the overall condition more severe. NCBI+1
20. Unknown factors
CHIME syndrome is extremely rare, with only a small number of reported patients worldwide. Because of this, there may be other causal or modifying factors that researchers have not yet discovered. Ongoing genetic and clinical research may find them in the future. PubMed+1
Symptoms
1. Ocular colobomas
Colobomas are gaps or “holes” in parts of the eye, such as the iris, retina, or optic nerve. In CHIME syndrome, they are usually present in both eyes. They can reduce vision and may cause problems with depth perception or light sensitivity. Orpha+1
2. Congenital heart defects
Many children have heart defects from birth. These may include holes between the heart chambers or problems with the valves. Some defects are mild and only need monitoring, while others may require medications or heart surgery. Orpha+1
3. Ichthyosiform dermatosis (scaly skin rash)
A key sign of CHIME is a red, scaly skin rash that looks like ichthyosis. It often appears in early life and can “move” from place to place (migratory). The skin may feel dry, thick, and itchy and may crack, making infections more likely. Orpha+1
4. Intellectual disability
Most children with CHIME have learning and thinking problems. They may sit, walk, talk, and learn later than other children. Some need special education and long-term developmental support. NCBI+1
5. Developmental delay
Beyond learning, general development is often delayed. Milestones like holding the head up, rolling, walking, and talking can all come later than expected. Early physical, occupational, and speech therapy can help. NCBI+1
6. Ear anomalies (unusual ear shape)
The ears may be low-set, have thick overfolded outer rims, or look differently shaped. These visible differences can be a clue to the diagnosis and may be linked to hearing loss. Orpha+1
7. Conductive hearing loss
Skin scaling and structural ear problems can block sound from reaching the inner ear. Children may not respond to quiet sounds or speech. Hearing aids, regular cleaning of the ear canal, and early speech therapy are often needed. Orpha+1
8. Seizures (epilepsy)
Some children develop seizures, which may start in early childhood. Seizures can be triggered or worsened by fever or high body temperature. Anti-seizure medicines and close neurologic care are important. Orpha+1
9. Characteristic facial features
Common facial features include a short broad head (brachycephaly), wide-spaced eyes (hypertelorism), slightly upward slanting eyelid openings, a flat midface, a flat area between nose and upper lip, and a wide mouth with extra creases around it. Orpha+1
10. Dental anomalies
Teeth may be widely spaced and square-shaped. There may also be delayed eruption or other dental problems, so regular dental assessment is important. Orpha+1
11. Growth delay
Some children are smaller than expected for their age and may have trouble gaining weight. Feeding problems (for example, difficulty sucking or swallowing) and repeated illness can also contribute to slow growth. NCBI+1
12. Feeding difficulties
Infants may have trouble breastfeeding or bottle feeding, may choke easily, or may be very slow feeders. Reflux and poor weight gain can occur. Tube feeding may be needed for some children. NCBI+1
13. Genitourinary anomalies
Some patients have kidney or urinary tract problems, such as hydronephrosis (swelling of the kidney due to urine build-up) or unusual uterus shape in girls. These problems may cause urinary infections or other complications. Springer+1
14. Behavior problems and irritability
Because of pain from skin cracks, itching, or seizures, children may be irritable, cry often, or have behavior issues. Communication difficulties can also make frustration worse. Support for both child and family is important.
15. Recurrent skin infections
Cracks in the skin and chronic rash can allow bacteria to enter easily. This can lead to repeated skin infections, which may be painful and need antibiotics. Good skin care and regular follow-up help lower this risk. Wiley Online Library+1
Diagnostic tests
Physical examination tests
1. Full general and growth examination
The doctor checks the child’s overall appearance, weight, height, and head size. They look for growth delay, body proportions, and general health. They also look for typical facial features, skin changes, and any breathing or heart distress. This first step helps the doctor suspect a syndromic condition like CHIME. Orpha+1
2. Detailed skin examination
The skin is examined from head to toe for red, scaly, thick patches and for cracks or infections. The doctor notes if the rash is “migratory,” meaning it moves to different body areas over time. This pattern is very suggestive of CHIME syndrome. Orpha+1
3. Eye examination with ophthalmoscope
Using a light and lens (ophthalmoscope), the doctor looks inside the eye to see the retina and optic nerve. They check for colobomas and other structural problems. This helps confirm the “C” (coloboma) part of CHIME. Orpha+1
4. Ear, nose, and throat (ENT) physical exam
The ENT specialist inspects the outer ear shape, the ear canal, and the eardrum. They look for thick skin build-up in the canal, fluid behind the eardrum, or other causes of conductive hearing loss. This supports the “E” (ear anomalies) part of CHIME. Orpha+1
Manual tests (bedside functional tests)
5. Developmental and neurological assessment
Doctors or therapists test muscle tone, reflexes, posture, and movement. They also assess milestones such as rolling, sitting, walking, speaking, and playing. This helps measure how much developmental delay and intellectual disability are present. NCBI+1
6. Bedside hearing tests
Simple tests are done to see how the child responds to sound. For example, the doctor may use soft sounds, rattles, or tuning forks and watch the child’s reaction. Later, more formal audiology tests confirm the degree of hearing loss. Orpha+1
7. Cardiac auscultation and pulse check
The doctor listens to the heart with a stethoscope to detect murmurs that may come from holes or valve problems. They also check pulses and look for signs of heart failure, such as swelling or breathing difficulty. If there are signs, more heart tests are done. Orpha+1
8. Basic manual vision and eye movement testing
In infants, doctors watch whether the baby tracks a face or toy and reacts to light. In older children, they test visual acuity and eye movements. Reduced vision or abnormal eye movements may point to colobomas or other eye issues needing specialist care. Orpha+1
Lab and pathological tests
9. Complete blood count (CBC) and basic blood tests
A CBC checks red blood cells, white blood cells, and platelets. Basic blood tests (such as electrolytes, glucose, and infection markers) help assess general health, infection risk, and treatment safety. These tests are not specific for CHIME but are important for overall care.
10. Liver and kidney function tests
Blood tests for liver enzymes, bilirubin, and kidney indicators (creatinine, urea) are done because some children with CHIME may have organ involvement or need medicines that stress the liver or kidneys. Abnormal results guide further testing and treatment. SciELO+1
11. Metabolic panel and electrolytes
These tests look at salts, acid–base balance, and other metabolic indicators. Since feeding problems and skin losses can affect hydration and electrolytes, regular checks help prevent complications, especially if the child is on special diets or strong drugs.
12. Serum transferrin isoelectric focusing or other glycosylation studies
Because CHIME is a congenital disorder of glycosylation, specialized blood tests can look for abnormal sugar patterns on transferrin (a blood protein) or other markers. This supports the idea that a glycosylation pathway is affected. PubMed+1
13. PIGL gene sequencing
Genetic testing of the PIGL gene is the key diagnostic test. A blood sample is taken, and the laboratory looks for harmful changes in the PIGL gene sequence. Finding two disease-causing mutations confirms the diagnosis of PIGL-related CHIME syndrome. PubMed+1
14. Broader gene panel or exome sequencing
Sometimes doctors order a larger panel of genes for neuroectodermal or ichthyosis syndromes, or even whole exome sequencing. This is useful when the diagnosis is unclear. It can still find PIGL mutations and may detect other gene changes that modify the disease. PubMed+1
Electrodiagnostic tests
15. Electroencephalogram (EEG)
An EEG records the electrical activity of the brain using electrodes placed on the scalp. In CHIME, it helps confirm and classify seizures and guide anti-seizure medication choice. It may show abnormal patterns even between visible seizures. Springer+1
16. Nerve conduction studies and electromyography (EMG)
If a child has low muscle tone, weakness, or unusual reflexes, nerve conduction tests and EMG may be used. They check how well nerves send signals to muscles. Although not always done in CHIME, they can rule out additional neuromuscular problems. NCBI+1
Imaging tests
17. Echocardiogram (heart ultrasound)
An echocardiogram uses sound waves to create moving pictures of the heart. It shows the size of the chambers, valve function, and any holes or abnormal connections. It is the main test to define congenital heart defects in CHIME syndrome. Orpha+1
18. Brain MRI
Magnetic resonance imaging (MRI) of the brain can show structural problems such as abnormal folding, white matter changes, or other developmental defects. These findings can help explain seizures and developmental delay and rule out other conditions. NCBI+1
19. Eye imaging (ocular ultrasound or OCT)
Eye specialists may use ultrasound or optical coherence tomography (OCT) to get detailed images of the eye’s internal structures. This helps measure the size and location of colobomas and plan follow-up for vision protection. Orpha+1
20. Renal and abdominal ultrasound
Ultrasound of the kidneys and abdomen looks for hydronephrosis, unusual kidney shape, or other organ anomalies that may occur in some children with CHIME. Detecting these early allows better management and monitoring of kidney function over time. Springer+1
Non-pharmacological treatments (therapies and other approaches)
(Because CHIME syndrome is ultra-rare and research is limited, these therapies are based on expert opinion and experience in similar complex genetic disorders.)
Comprehensive developmental and early-intervention therapy
Early-intervention programs include physical, occupational, and speech therapy starting in infancy. The purpose is to support motor skills, communication, and daily-living skills as early as possible. Therapists use play-based exercises, simple games, and routines to stimulate movement, language, and problem-solving. The mechanism is “neuroplasticity”: the young brain can build new connections when it is stimulated repeatedly in a safe, structured way.AccessPediatrics+1
Physiotherapy for posture, balance, and walking
Many children with CHIME syndrome have low muscle tone, wide-based gait, and poor coordination. Physiotherapy aims to strengthen muscles, improve posture, and reduce falls. Therapists may use stretching, balance training, and walking practice with support devices if needed. Over time, repeated movement training helps the nervous system learn more efficient patterns, which can reduce fatigue and improve independence in walking and playing.AccessPediatrics+1
Occupational therapy for daily skills and hand use
Occupational therapists help children learn day-to-day skills like feeding, dressing, toileting, and using their hands for writing or play. The purpose is to increase independence and reduce caregiver burden. They may adapt clothing, utensils, and school tools to match the child’s abilities. Mechanistically, repeated practice with graded challenges and adaptive equipment helps the child’s brain and muscles learn more coordinated hand and self-care movements.AccessPediatrics+1
Speech, language, and feeding therapy
Feeding difficulties and delayed speech are common. Speech-language pathologists help with safe swallowing techniques, texture adjustments, and communication strategies. They may train parents in positioning, pacing feeds, and using thickened liquids if needed. For speech, they use simple words, pictures, and sometimes communication devices. The mechanism is repeated practice of speech sounds and safe swallowing patterns to build stronger, more coordinated mouth and throat muscles, while preventing choking and aspiration.AccessPediatrics+1
Low-vision support and visual rehabilitation
Eye colobomas can cause reduced or distorted vision. Low-vision specialists assess what a child can see and recommend glasses, magnifiers, large-print materials, and improved lighting. The purpose is to help the child use their remaining vision as effectively as possible. The mechanism is environmental adaptation—changing font size, contrast, and lighting so the brain can process available visual information more easily, reducing strain and improving learning.Orpha+2Wikipedia+2
Hearing rehabilitation and communication support
Children may have conductive hearing loss and abnormal auditory signals. Audiologists test hearing early and offer hearing aids or other devices. The purpose is to give the brain clear sound input while language is developing. Early, consistent amplification helps the auditory system and language centers in the brain develop better, which improves speech, understanding, and social interaction. Parents and teachers are also taught to speak clearly, face the child, and use visual supports.Orpha+2AccessPediatrics+2
Structured skin-care program
The ichthyosiform dermatosis causes dry, thick, itchy skin. A daily routine of short lukewarm baths, gentle non-soap cleansers, and thick emollients (fragrance-free creams or ointments) is essential. The purpose is to keep the skin barrier moist and flexible, reduce cracking, and prevent infections. Mechanistically, emollients replace missing skin lipids and water, sealing the outer layer and reducing transepidermal water loss. Regular gentle exfoliation with soft cloths may help loosen scales without damage.Orpha+2AccessPediatrics+2
Cardiac rehabilitation and activity planning after heart surgery
When heart defects (such as ventricular septal defect or tetralogy of Fallot) are repaired, children need careful activity planning. Cardiac rehabilitation uses monitored exercise to strengthen the heart and lungs safely. The purpose is to improve stamina and reduce breathlessness. The mechanism is graded aerobic and strength training that slowly conditions heart muscle and circulation, guided by cardiology teams to avoid overload.AccessPediatrics+2Europe PMC+2
Behavioral therapy and emotional support
Some children show behavioral outbursts, especially when itchy skin and pruritus worsen at puberty. Behavior therapists and psychologists help identify triggers (itching, pain, frustration, sensory overload) and teach coping skills, routines, and positive reinforcement strategies. The mechanism is behavior shaping: linking calm behaviors to rewards and helping the child express discomfort in safer ways, while parents learn consistent responses and self-care.AccessPediatrics+2Europe PMC+2
Infection-prevention education and hygiene routines
Frequent sinus, ear, or skin infections are reported. Families are taught proper handwashing, gentle skin care, nasal and dental hygiene, and early recognition of infection signs. The purpose is to reduce hospital admissions and limit antibiotic use. Mechanistically, breaking transmission routes and keeping skin intact lowers the chance that bacteria or viruses can enter the body and cause serious illness.AccessPediatrics+2Europe PMC+2
Genetic counseling for the family
Genetic counselors explain how CHIME syndrome is inherited, the chances of recurrence in future pregnancies, and options such as carrier testing and prenatal or preimplantation genetic diagnosis where available. The purpose is informed reproductive decision-making and emotional support. The mechanism is education and risk communication, helping parents understand autosomal recessive inheritance and plan safely for the future.Orpha+2National Organization for Rare Disorders+2
Social work, respite, and caregiver support
Caring for a child with CHIME syndrome is physically and emotionally demanding. Social workers help families access financial aid, equipment, special schooling, and respite care. The purpose is to reduce caregiver burnout and improve quality of life for the whole family. By sharing tasks and connecting families with support groups, stress hormones can fall, and parents can maintain their own health and ability to care for the child.National Organization for Rare Disorders+1
Drug treatments (symptom-based medical management)
(No medicine can cure CHIME syndrome. Drugs are used to manage seizures, skin disease, infections, heart problems, and other complications. All doses must be set by a specialist.)
Modern antiseizure medicines – levetiracetam (Keppra) and others
Seizures in CHIME syndrome are usually treated with standard antiseizure drugs. Levetiracetam (brand name Keppra) is an antiepileptic that reduces abnormal electrical activity in the brain by binding to synaptic vesicle protein SV2A. It is FDA-approved for partial-onset, myoclonic, and primary generalized tonic-clonic seizures in children and adults, using weight-based dosing. Common side effects include sleepiness, dizziness, irritability, and mood changes. Treatment choice and timing are individualized by neurologists.AccessPediatrics+2FDA Access Data+2
Broad-spectrum antiseizure medicines – valproic acid / divalproex
Valproic acid (Depakene) and divalproex (Depakote) increase levels of gamma-aminobutyric acid (GABA) and block certain sodium and calcium channels, stabilizing brain activity. They are FDA-approved for many seizure types and sometimes used in complex epilepsies like those seen in CHIME syndrome. Typical pediatric dosing is weight-based and carefully adjusted. Side effects can include stomach upset, weight gain, tremor, liver toxicity, and rare pancreatitis or serious birth-defect risk if used in pregnancy.FDA Access Data+3AccessPediatrics+3FDA Access Data+3
Additional antiseizure medicines (lamotrigine, topiramate, others)
If seizures are not controlled, doctors may add or switch to other antiepileptic drugs such as lamotrigine, topiramate, or newer agents. These medicines act on sodium channels, glutamate receptors, or GABA pathways to calm over-active nerve cells. Choice depends on seizure type, other medicines, and side-effect profile. Possible side effects include rash (which can be serious with lamotrigine), cognitive slowing, appetite changes, and kidney stones with topiramate. In CHIME syndrome, neurologists balance seizure control with cognitive and behavioral effects.AccessPediatrics+2Europe PMC+2
Topical emollients and keratolytic preparations for skin
Although many emollients are over-the-counter products, dermatologists sometimes prescribe stronger urea- or lactic acid–containing creams or ointments to soften thick scales. These agents help break down the outer layer of dead skin cells, improving texture and flexibility. Side effects may include mild stinging or irritation, especially on broken skin. Regular use alongside simple petrolatum-based moisturizers can reduce itching and the risk of cracks that invite infection.Orpha+2AccessPediatrics+2
Topical corticosteroids for inflamed or itchy skin
Low- to medium-potency topical corticosteroids, such as hydrocortisone or triamcinolone creams, may be used in short courses when skin becomes very inflamed and itchy. They work by reducing local immune activity and inflammation in the skin. Doctors prescribe the strength, amount, and duration, especially in children, to avoid side effects like thinning of the skin, stretch marks, or hormone suppression when used too long or over large areas.Orpha+2AccessPediatrics+2
Oral antihistamines for itch control and sleep
Non-sedating antihistamines such as cetirizine or loratadine are sometimes used during the day to reduce itch, while sedating antihistamines like hydroxyzine may be used at night to help sleep when pruritus is severe. These medicines block histamine receptors, lowering the allergic-type signal that contributes to itching. Side effects can include drowsiness (especially with older antihistamines), dry mouth, and, rarely, heart rhythm changes at high doses.Orpha+2Chemwatch+2
Antibiotics for recurrent skin, ear, or sinus infections
Children with CHIME syndrome may need repeated antibiotic courses for bacterial skin infections, ear infections, or sinusitis. Doctors choose the antibiotic based on likely bacteria, local resistance patterns, and culture results where possible. The mechanism is direct killing or growth inhibition of bacteria to clear infection and prevent complications like sepsis or hearing damage. Side effects vary by drug but can include diarrhea, allergic reactions, and, with repeated courses, disruption of gut microbiota.AccessPediatrics+2Europe PMC+2
Cardiac medications before or after heart surgery
Before or after repair of congenital heart defects, some children need medicines such as ACE inhibitors, beta-blockers, or diuretics. These drugs reduce the workload on the heart, control blood pressure, and manage fluid overload. For example, ACE inhibitors relax blood vessels, making it easier for the heart to pump blood. Side effects can include low blood pressure, cough, dizziness, or changes in kidney function and electrolytes, so cardiologists monitor lab tests and symptoms closely.AccessPediatrics+2Europe PMC+2
Analgesics and antipyretics (paracetamol, ibuprofen)
Pain and fever from infections, surgery, or skin inflammation are usually treated with paracetamol (acetaminophen) or ibuprofen. These medicines reduce prostaglandin production in the brain and body, lowering fever and pain perception. Doses must be strictly weight-based in children. Side effects include liver toxicity with paracetamol overdose and stomach or kidney problems with excessive ibuprofen. Parents should never exceed the recommended dose or mix multiple medicines without medical advice.AccessPediatrics+2National Organization for Rare Disorders+2
Nutritional supplements prescribed as medicines (vitamin D, calcium, iron)
If blood tests show vitamin D deficiency, low calcium, or anemia, doctors may prescribe specific doses of vitamin D, calcium, or iron. These supplements support bone strength, immune function, and oxygen-carrying capacity. They are given in carefully calculated doses based on age, weight, and lab results. Over-supplementation can be harmful, causing high calcium, constipation, or organ damage, so they must be taken exactly as prescribed and monitored with follow-up tests.National Organization for Rare Disorders+1
Dietary molecular supplements (under medical supervision only)
(There is no strong evidence that any supplement can cure CHIME syndrome. Supplements are used only to correct proven deficiencies or support general health.)
Omega-3 fatty acids (fish oil or algae-based)
Omega-3 supplements are sometimes used to support heart health, brain function, and reduce inflammation. They may slightly improve skin dryness and inflammation in some conditions. Typical doses vary by age and body weight and must be set by clinicians to avoid bleeding risks at high doses. Omega-3s work by being built into cell membranes and changing inflammatory signaling molecules called eicosanoids, which can make inflammation milder in some tissues.National Organization for Rare Disorders+1
Vitamin D supplement
Vitamin D helps regulate calcium and phosphate balance, bone mineralization, and immune function. Children with chronic illness, limited sun exposure, or anticonvulsant therapy may be at risk of low vitamin D. Doctors prescribe age- and weight-appropriate doses, sometimes higher at first to correct deficiency. Vitamin D acts via nuclear receptors to change gene expression in bone cells and immune cells. Too much can cause high calcium, nausea, or kidney damage, so monitoring is essential.National Organization for Rare Disorders+1
Calcium supplementation
If diet and vitamin D are not enough to maintain normal calcium levels, calcium supplements may be used. Calcium supports bone strength, heart rhythm, and muscle contraction. Tablets or liquid are given with food in doses chosen by the clinician. Calcium ions act as key signals inside many cells and help build the mineral matrix of bones. Excess calcium can cause constipation, kidney stones, and, rarely, heart rhythm problems, so balance is crucial.National Organization for Rare Disorders+1
Multivitamin tailored for children with chronic illness
A pediatric multivitamin can help cover small gaps in intake of vitamins such as A, B-complex, C, E, and trace minerals. The purpose is to support general growth, immunity, and energy metabolism when appetite is limited or needs are higher. The mechanism is simple: each vitamin supports specific enzyme systems and cell functions. Doses must not exceed recommended daily allowances unless a doctor specifies otherwise, because fat-soluble vitamins can build up and cause toxicity.National Organization for Rare Disorders+1
Probiotic preparations
Probiotics are live “friendly” bacteria or yeasts that may help balance gut microbiota, especially in children who receive frequent antibiotics. Some strains may reduce diarrhea or antibiotic-associated gut upset. Doses are measured in colony-forming units (CFU) and chosen by the doctor. Mechanistically, probiotics compete with harmful bacteria, produce beneficial substances, and may modulate immune responses in the gut. Evidence is growing but still limited in rare diseases like CHIME.National Organization for Rare Disorders+1
Zinc supplementation (if deficient)
Zinc is essential for immune function, wound healing, and skin integrity. Low zinc can worsen skin problems. If blood tests show deficiency, doctors prescribe zinc in carefully controlled doses. Zinc acts as a co-factor for many enzymes involved in DNA repair and immune responses. Too much zinc can cause nausea, abdominal pain, and copper deficiency, so supplements should never be taken at high doses without supervision.National Organization for Rare Disorders+1
Iron supplements (for documented anemia)
Chronic illness, poor intake, or repeated infections can lead to iron-deficiency anemia. Iron supplements rebuild iron stores so the body can make hemoglobin to carry oxygen. Doses are weight-based and adjusted by blood tests. Mechanistically, iron is incorporated into hemoglobin and many enzymes. Side effects include stomach upset, constipation, dark stools, and, if overdosed, serious poisoning, so iron must be stored safely away from children.National Organization for Rare Disorders+1
Selenium and antioxidant micronutrients (when indicated)
Selenium and other antioxidants help protect cells from oxidative stress. In theory, they may support heart and muscle function. Supplements are only used if labs and diet history suggest deficiency. They work as parts of enzymes like glutathione peroxidase, which neutralizes harmful reactive oxygen species. Too much selenium can cause hair loss, nail changes, and nerve problems, so dosing must be cautious and guided by a clinician.National Organization for Rare Disorders+1
Coenzyme Q10 (CoQ10)
CoQ10 is a molecule involved in mitochondrial energy production and acts as an antioxidant. In some mitochondrial or metabolic disorders, CoQ10 is used to try to support energy levels and reduce fatigue, though evidence in CHIME is lacking. It is given as capsules or liquid, with doses adjusted by weight. CoQ10 participates in electron transport in mitochondria, helping cells generate ATP. Side effects are usually mild, such as stomach upset.National Organization for Rare Disorders+1
Medium-chain triglyceride (MCT) oil (if advised by dietitian)
MCT oil contains fats that are easier for the body to absorb and use quickly as energy. In children with poor weight gain or fat absorption, small amounts may be used under dietitian guidance. MCTs are absorbed directly into the portal circulation and transported to the liver, where they are rapidly oxidized for energy. Too much can cause diarrhea or cramping, so careful titration is necessary.National Organization for Rare Disorders+1
Immunity-booster, regenerative, and stem-cell-related drugs
For neuroectodermal dysplasia, CHIME type, there are currently no approved stem cell drugs, gene therapies, or specific immune-boosting medicines proven to treat the core disease. Research in congenital disorders of glycosylation and rare ectodermal dysplasias is ongoing, but most approaches are still experimental or focused on supportive care, not cure.Orpha+1
Vaccines as key immune protection
The most effective “immune booster” for children with CHIME syndrome is up-to-date vaccination according to national schedules, including influenza and pneumococcal vaccines when recommended. Vaccines train the immune system to recognize specific germs by presenting harmless antigens, so the body can respond more quickly during real infection. Side effects are usually mild (fever, soreness). Decisions about extra vaccines are made by the pediatrician or immunologist.National Organization for Rare Disorders+1
Intravenous immunoglobulin (IVIG) in selected cases
If a child with CHIME syndrome shows immunoglobulin deficiency or unusually severe recurrent infections, an immunologist may consider IVIG, a blood-derived product containing pooled antibodies. Its purpose is to provide ready-made antibodies to fight infection and modulate immune responses. IVIG is given in hospital by infusion and can cause headache, fever, or rare serious reactions. It is not routine for CHIME; it is reserved for special situations.National Organization for Rare Disorders+1
Hematopoietic stem cell transplant (HSCT) – research context
In some other congenital disorders of glycosylation or severe immune deficiencies, hematopoietic stem cell transplant has been tried to replace defective blood and immune cells. In CHIME syndrome, HSCT is not a standard therapy and would only be considered in experimental or very specific situations. The mechanism is replacing the bone marrow with donor stem cells, but it carries major risks like infection, graft-versus-host disease, and organ damage.Orpha+1
Experimental gene or enzyme-targeted therapies
Scientists are exploring gene therapy and small molecules that may correct steps in glycosylphosphatidylinositol (GPI) anchor synthesis in related conditions, because PIGL is part of this pathway. None of these therapies are approved for CHIME syndrome yet. The idea is to restore or bypass the faulty enzyme step so proteins can be correctly anchored to cell membranes. At present, such work is only at the laboratory or early research level.Orpha+1
Growth factors and supportive hematologic drugs
In certain blood complications (like associated leukemia described in a few CHIME cases), hematologists may use growth factors such as G-CSF or erythropoietin to stimulate white blood cell or red blood cell production. These drugs act on bone marrow receptors to speed up cell production. They are not used routinely in CHIME syndrome, only when indicated by a specific hematologic problem and always under specialist control.AccessPediatrics+1
Clinical trial medicines
Some families may be offered participation in clinical trials of drugs that target seizures, skin disease, or metabolic pathways. These medicines are carefully tested under strict protocols. The purpose is to learn whether a new drug is safe and effective. Mechanisms vary, but participation always requires detailed informed consent and close medical monitoring. Families should discuss benefits and risks with their care team before entering any trial.National Organization for Rare Disorders+1
Surgeries (procedures and why they are done)
Surgical repair of congenital heart defects
Many children with CHIME syndrome have serious heart defects like ventricular septal defect, tetralogy of Fallot, or great-artery transposition. Cardiac surgeons repair holes, narrowings, or abnormal vessel connections to improve oxygen delivery and heart function. The procedure may involve open-heart surgery with a heart–lung machine. The goal is to prevent heart failure, poor growth, and dangerous low-oxygen episodes and to improve long-term survival and activity levels.AccessPediatrics+2Europe PMC+2
Eye surgery and low-vision procedures for coloboma
Eye colobomas are gaps or defects in the eye structure that can affect vision. In some cases, surgery can repair associated problems such as cataracts, retinal detachment, or eyelid malformations. The aim is to preserve as much vision as possible and prevent complications. Even when surgery cannot fully correct the coloboma, procedures plus low-vision aids can improve daily functioning and safety.Orpha+2Wikipedia+2
Cleft palate repair
Some individuals with CHIME syndrome have cleft palate or bifid uvula. Surgeons can close the palate to improve feeding, speech, and reduce ear infections. The procedure brings together muscle and mucosal layers in the roof of the mouth. This helps create proper pressure for speech sounds and separates the mouth from the nasal cavity, which also lowers the risk of food entering the nose and middle ears.AccessPediatrics+1
Ear surgery and tympanostomy tubes
Recurrent middle-ear infections and conductive hearing loss may be treated with insertion of ventilation (“grommet”) tubes into the eardrum. This minor surgery lets fluid drain and air enter the middle ear, reducing infections and improving hearing. In some cases, reconstructive ear surgery may be done to correct external ear anomalies for functional or cosmetic reasons, improving hearing-aid fitting and self-esteem.AccessPediatrics+2Europe PMC+2
Orthopedic surgery for foot or limb deformities
Occasional clubfoot or toe and finger anomalies can interfere with walking and hand function. Orthopedic surgeons may perform tendon releases, bone realignment, or corrective casting and surgery to improve alignment. The goal is better mobility, pain reduction, and easier use of shoes and aids. Early correction often allows more natural development of gait and posture as the child grows.AccessPediatrics+1
Preventions (what can and cannot be prevented)
Because neuroectodermal dysplasia, CHIME type is a genetic condition, the underlying disease usually cannot be fully prevented once conception has occurred. However, several steps can reduce risks and complications:
Genetic counseling before future pregnancies – carrier parents can learn recurrence risks and options like carrier testing and prenatal diagnosis.Orpha+1
Prenatal or preimplantation genetic diagnosis where available – in some regions, families may choose testing embryos or pregnancies for PIGL mutations to make informed reproductive decisions.Orpha+1
Early diagnosis and registration with a specialist center – early recognition allows timely seizure control, heart monitoring, and skin care, which can prevent serious complications.AccessPediatrics+1
Complete vaccination schedule – helps prevent serious infections that can be particularly dangerous in children with heart or lung problems.National Organization for Rare Disorders+1
Good skin-care routines – daily emollients, gentle bathing, and early treatment of cracks can prevent severe infections and hospital admissions.Orpha+2AccessPediatrics+2
Safe seizure management – regular medicine review, good sleep, and prompt fever control can reduce seizure triggers and injuries from falls.AccessPediatrics+2FDA Access Data+2
Regular hearing and vision checks – early detection of changes allows timely adjustment of hearing aids or vision aids, preventing avoidable learning delays.Orpha+2AccessPediatrics+2
Dental and oral hygiene – regular brushing, fluoride, and dental visits help prevent caries and infections, which can be more frequent in complex syndromes.National Organization for Rare Disorders+1
Heart-healthy habits – avoiding tobacco smoke exposure, encouraging age-appropriate physical activity after cardiologist approval, and a balanced diet support long-term heart health in repaired defects.AccessPediatrics+1
Avoiding unproven treatments – staying away from unregulated “stem cell cures,” extreme diets, or online miracle treatments reduces risk of harm and wasted resources. Families should always check new ideas with their care team.National Organization for Rare Disorders+1
When to see doctors urgently or regularly
Families should keep regular appointments with their pediatrician and specialists, but certain signs need urgent medical attention:
New or worsening seizures, especially if they last longer than usual, happen in clusters, or the child does not wake properly afterwards.AccessPediatrics+1
Breathing difficulty, bluish lips, or chest pain, which may signal heart or lung problems.AccessPediatrics+1
High fever, spreading skin redness, or pus, suggesting a serious skin or soft-tissue infection.AccessPediatrics+1
Sudden change in behavior or consciousness, such as unusual sleepiness, confusion, or violent outbursts very different from usual patterns.AccessPediatrics+1
Feeding refusal, vomiting, or failure to gain weight, which may need urgent nutritional and medical review.AccessPediatrics+1
New vision or hearing loss, like bumping into objects, not responding to sound, or complaining of dark areas in vision.Orpha+2AccessPediatrics+2
Routine follow-up visits are used to review seizures, adjust medicines, check growth and development, monitor heart and kidney function, and update therapy plans.
What to eat and what to avoid
(Diet must always be personalized by a dietitian, especially if there are heart, kidney, or swallowing problems.)
Helpful foods to focus on
A balanced diet with plenty of fruits, vegetables, whole grains, and lean protein supports growth, immunity, and wound healing. Soft, moist foods can help children with chewing or swallowing difficulties. Healthy fats from fish, nuts (if safe), and plant oils support skin barrier and brain development. Small, frequent meals may be easier for children who tire easily or have feeding issues.National Organization for Rare Disorders+1
Adequate fluids
Enough water and appropriate fluids keep the skin and mucous membranes hydrated and support kidney function, especially if medicines like antiseizure drugs are used. For children with heart disease, fluid limits may be needed, so the cardiologist’s advice is essential.AccessPediatrics+1
Foods rich in iron and vitamins
Iron-rich foods (lean meat, fish, eggs, fortified cereals, legumes) and vitamin-C-rich fruits help prevent anemia and support immune function. Dairy or fortified alternatives provide calcium and vitamin D for bones. These should be part of daily meals unless specific allergies or intolerances exist.National Organization for Rare Disorders+1
What to limit or avoid
Very salty, heavily processed foods should be limited, especially in children with heart defects or high blood pressure, because excess sodium increases fluid retention. Very sugary drinks and snacks add calories without nutrients and can worsen dental problems and weight issues. Caffeine-containing drinks and energy drinks may disturb sleep and could potentially trigger seizures in some people, so they are best avoided.AccessPediatrics+2National Organization for Rare Disorders+2
Avoid extreme or “detox” diets
Strict elimination diets, fasting “detox” programs, or very high-dose “natural” supplements advertised online as cures are not supported by evidence for CHIME syndrome and can be dangerous. They can lead to malnutrition, electrolyte imbalance, or interactions with prescribed medicines. Families should always discuss any major diet change with the medical team first.National Organization for Rare Disorders+1
Frequently asked questions (FAQs)
1. Is there a cure for neuroectodermal dysplasia, CHIME type?
At present, there is no cure for CHIME syndrome. Treatment focuses on managing seizures, heart defects, skin problems, hearing and vision issues, and developmental challenges. Research into genetic and metabolic therapies is ongoing, but nothing is yet approved for this specific condition.Orpha+1
2. What causes this condition?
CHIME syndrome is caused by changes (mutations) in the PIGL gene, which affects how certain proteins are attached to cell membranes through GPI anchors. It is inherited in an autosomal recessive pattern, meaning both parents usually carry one changed copy but are healthy themselves.Orpha+1
3. How common is CHIME syndrome?
It is extremely rare, with fewer than 1,000 people estimated in the United States and only a handful of detailed case reports worldwide. This rarity is why information is limited and why finding experienced specialists can be challenging.GARD Information Center+2AccessPediatrics+2
4. Will my child’s seizures last for life?
Some children with CHIME syndrome continue to have seizures long-term, while others achieve better control with medicine and growth. It is impossible to predict for each child. Regular follow-up with a pediatric neurologist and careful adjustment of antiseizure drugs give the best chance of reducing seizure frequency and severity.AccessPediatrics+2FDA Access Data+2
5. Can my child go to school?
Many children with CHIME syndrome can attend school with support. They often need special education plans, classroom aids, low-vision tools, and hearing support. Early-intervention programs, speech therapy, and occupational therapy can make school participation easier and more successful.AccessPediatrics+2National Organization for Rare Disorders+2
6. What is the outlook for heart problems?
With modern cardiac surgery and follow-up, many heart defects in CHIME syndrome can be repaired or improved. Outcomes depend on the specific defect and other health issues. Lifelong cardiology follow-up is still needed to monitor heart function and valve status.AccessPediatrics+2Europe PMC+2
7. Do skin problems improve with age?
The ichthyosiform rash can change over time. Some reports describe worsening itch and flares around puberty. With consistent skin care and appropriate medicines during flares, many people can keep symptoms more comfortable, but dryness often remains lifelong.AccessPediatrics+2Europe PMC+2
8. Can siblings also be affected?
If both parents are carriers of a PIGL mutation, each pregnancy has a 25% chance of an affected child, a 50% chance of a carrier child, and a 25% chance of a child with no mutation. Genetic counseling can help families understand these risks and options for future pregnancies.Orpha+1
9. Are vaccines safe for children with CHIME syndrome?
In most cases, routine vaccines are safe and strongly recommended because they prevent serious infections that can be very dangerous in children with heart and neurological problems. If a child has specific immune issues or is on certain medicines, the care team may adjust the schedule. Parents should always follow the advice of their pediatrician or immunologist.National Organization for Rare Disorders+1
10. Can adults with CHIME syndrome live independently?
Ability to live independently varies widely. Some people may always need full-time support because of intellectual disability, behavior challenges, or medical needs. Others may achieve partial independence with structured support, supported housing, and continued therapy. Planning for adult care, guardianship, and community services is important as children grow older.AccessPediatrics+1
11. Are there support groups for families?
Yes. Organizations for ectodermal dysplasias and rare diseases can connect families with similar experiences, resources, and emotional support. Examples include national ectodermal dysplasia foundations and rare disease organizations listed on GARD, Orphanet, and Global Genes.GARD Information Center+2National Organization for Rare Disorders+2
12. Should we try alternative or “natural” therapies?
Some families explore complementary approaches like gentle massage, relaxation techniques, or safe nutritional counseling. These can sometimes improve comfort and stress levels. However, “miracle cures,” unregulated stem cell injections, or high-dose supplements are risky and not supported by evidence for CHIME syndrome. Always discuss any alternative therapy with your medical team first.National Organization for Rare Disorders+1
13. How can parents cope emotionally?
Caring for a child with a rare, complex disease is emotionally heavy. Counseling, parent support groups, respite services, and honest communication with the care team can help. It is important for caregivers to protect their own mental health, rest when possible, and ask for help early rather than waiting until they feel overwhelmed.National Organization for Rare Disorders+1
14. How can we help teachers understand CHIME syndrome?
Parents can share simple written information about the child’s condition, main symptoms (seizures, vision or hearing problems, skin issues), emergency seizure plans, and tips for communication. Inviting teachers to join care-team meetings and providing contact details for therapists or doctors helps build a coordinated support system at school.AccessPediatrics+1
15. Where can we find reliable medical information?
Trusted sources include GARD (Genetic and Rare Diseases Information Center), Orphanet, national ectodermal dysplasia organizations, and major children’s hospitals or academic centers. These sites offer vetted, regularly updated information, unlike many unregulated websites or social media posts.Global Genes+3GARD Information Center+3Orpha+3
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: December 31, 2025.
