Neuroectodermal dysplasia, CHIME type (usually called CHIME syndrome), is a very rare genetic condition. It mainly affects the skin, eyes, heart, brain, and ears. Doctors place it in a group called ectodermal dysplasia syndromes, which means parts of the body that come from the outer layer of the embryo (skin, hair, teeth, nerves, eyes, ears) do not form in the usual way.GARD Information Center+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
The word CHIME is an acronym made from the main features: Coloboma of the eye (missing piece in eye structures), Heart defects, Ichthyosiform dermatosis (dry, scaly “fish-like” rash), Mental or intellectual disability, and Ear anomalies, often with hearing loss or epilepsy (seizures). Only a very small number of people with this condition have been reported worldwide.GARD Information Center+2PMC+2
CHIME syndrome is a congenital (present from birth) disorder. It follows an autosomal recessive inheritance pattern. This means a child is affected when they receive one faulty copy of the same gene from each parent. The gene involved is called PIGL, which helps make special “anchor” molecules (GPI anchors) that hold many proteins on the surface of cells.PMC+2University of Chicago Genetic Services+2
Other names
Doctors and genetic databases use several other names for neuroectodermal dysplasia, CHIME type. All of these names are talking about the same condition:
Neuroectodermal dysplasia, CHIME type is also called:
CHIME syndrome
Zunich neuroectodermal syndrome
Zunich–Kaye syndrome
Neuroectodermal syndrome, Zunich type
PIGL-CDG (PIGL-related congenital disorder of glycosylation)
Congenital disorder of glycosylation due to PIGL deficiency
Coloboma–congenital heart disease–ichthyosiform dermatosis–intellectual disability–ear anomalies syndrome
These different names are used in rare-disease databases such as Orphanet, Monarch Initiative, Malacards and ZFIN, and they all describe the same rare neuroectodermal dysplasia.MalaCards+3National Organization for Rare Disorders+3Global Genes+3
Types
There is no strict official “type 1, type 2” system for CHIME syndrome yet, because it is extremely rare and only a few patients have been described. However, in medical papers and case reports, doctors sometimes speak about patterns that look like “types”:
Typical or classic CHIME syndrome
This describes people who have the full set of main features: eye colobomas, heart defects, migratory ichthyosiform skin rash, clear intellectual disability, and ear changes with hearing loss and sometimes seizures. This pattern was seen in most of the very early cases that were first reported.PMC+1Mild or attenuated CHIME syndrome
Some newer reports describe children with confirmed PIGL gene changes who have a less severe form. They may have the skin rash and learning difficulties but milder eye or heart problems, or fewer physical differences. Doctors sometimes call this a “mild phenotype” of the same genetic disease.Wiley Online Library+1CHIME within the wider PIGL-related congenital disorders of glycosylation
CHIME syndrome is now considered part of a larger group of conditions called congenital disorders of glycosylation (CDG). In this group, different genes in the same biochemical pathway can give overlapping problems with brain, heart, skin, and growth. PIGL-CDG (CHIME) is one specific member of this group.Annals of Translational Medicine+1
When writing for patients and families, it is usually enough to say that neuroectodermal dysplasia, CHIME type and CHIME syndrome are the same condition, and that severity can vary from person to person.
Causes and disease mechanism
In reality, there is one main proven cause of neuroectodermal dysplasia, CHIME type: harmful changes (mutations) in the PIGL gene. To make the list you asked for, the 20 “causes” below each describe a different aspect or consequence of this one genetic cause, not 20 separate unrelated causes.
PIGL gene mutation
The direct cause is a disease-causing change in both copies of the PIGL gene. This gene gives instructions for an enzyme in the endoplasmic reticulum that helps make GPI (glycosylphosphatidylinositol) anchors. When PIGL does not work properly, many cell-surface proteins cannot attach to the cell membrane in the normal way.PMC+1Autosomal recessive inheritance
The condition is autosomal recessive. This means each parent usually carries one changed PIGL gene and one normal gene. They are often healthy carriers. When two carriers have a child, there is a 25% chance in each pregnancy that the child will receive both changed copies and will be affected.University of Chicago Genetic Services+1Homozygous or compound heterozygous variants
A child can be affected when they inherit the same mutation from both parents (homozygous) or two different harmful mutations, one from each parent (compound heterozygous). Both situations lead to too little or no functional PIGL enzyme.ZFIN+1Disruption of GPI-anchor biosynthesis
PIGL is required in an early step of building GPI anchors, which are special sugar-lipid structures that hold many proteins on the outer surface of cells. When this step is blocked, many GPI-anchored proteins are missing or reduced, especially in tissues like skin, brain, heart, and ears.Annals of Translational Medicine+1Loss of normal ectodermal development
Ectoderm-derived tissues (skin, hair, teeth, some parts of the nervous system and sensory organs) depend on properly anchored proteins for signaling and cell-cell contact. Faulty GPI anchors disturb these signals, which leads to abnormal development of skin, eyes, ears, and other ectodermal structures.Orpha+1Abnormal neuroectodermal development
The neuroectoderm gives rise to parts of the brain, eyes and nerves. In CHIME syndrome, loss of some GPI-anchored proteins during early brain development probably disrupts normal brain wiring and eye formation. This helps explain seizures, intellectual disability and eye colobomas.ResearchGate+1Disturbed skin barrier formation
The PIGL defect affects skin cells and the way they stick together. This contributes to the ichthyosiform dermatosis, a migratory, dry, scaly rash that often appears in infancy and may move over the body.Abnormal heart formation (cardiac morphogenesis)
GPI-anchored proteins are important for signaling pathways that guide the forming heart. In CHIME syndrome, this disruption can lead to congenital heart defects such as ventricular septal defect or more complex abnormalities like tetralogy of Fallot.PMC+1Disrupted ear and hearing development
Middle and inner ear structures can form abnormally when key proteins are missing from cell surfaces. This is why many children with CHIME syndrome have ear shape differences and conductive hearing loss, sometimes due to extra skin scales in the ear canal and abnormal bones of the middle ear.GARD Information Center+1Disturbed eye development (coloboma)
In normal eye development, tissues at the back or front of the eye close together. In CHIME syndrome, this closure can be incomplete, leaving a coloboma (a missing piece) in the iris, retina, or optic nerve. This is likely related to abnormal signaling caused by missing GPI-anchored proteins.Orpha+1Failure of normal brain network wiring
Neural cells also use GPI-anchored proteins for communication. Their loss may disturb the growth of brain connections, leading to developmental delay, learning difficulties, and wide-based or clumsy walking, as described in reported cases.AccessPediatrics+1Seizure tendency from cortical dysregulation
Abnormal brain networks, plus structural changes seen on brain imaging in some patients, create an unstable electrical environment in the cortex. This makes seizures (epilepsy) more likely, especially with fever or high environmental temperature.ResearchGate+1Kidney and urinary tract malformations
Some reported patients have kidney or urinary tract anomalies (for example, duplicated collecting systems). These also arise from disturbed organ development during the embryo stage, likely related to the same PIGL-GPI anchor pathway.AccessPediatricsCraniofacial skeletal changes
GPI-anchored proteins influence craniofacial bone and cartilage growth. Their loss can cause features such as broad nasal bridge, short philtrum, and dental anomalies in affected children.AccessPediatrics+1Autosomal recessive family pattern
Families with more than one affected child often show that both parents are healthy carriers. This family pattern is itself a “cause” pathway, because the genetic manner of inheritance makes recurrence in siblings more likely if carrier parents have more children.DoveMed+1Consanguinity (parents related by blood)
In some rare genetic disorders, parents who are cousins or more closely related have a higher chance of carrying the same rare gene variant. When this happens with PIGL mutations, the risk of a child inheriting two changed copies is higher. For CHIME, consanguinity has been noted in some, but not all, reported families.DoveMed+1New (de novo) mutations
In some rare genetic diseases, a mutation may appear for the first time in the child, without being present in either parent. This is called a de novo mutation. It is possible, though not yet well documented, that some PIGL mutations in CHIME syndrome arise this way.Broader CDG pathway vulnerability
CHIME syndrome belongs to the wider group of congenital disorders of glycosylation, where many different enzymes in the glycosylation pathways can be affected. Disturbance of this whole pathway is a general “cause environment” for multi-system problems like those seen in CHIME.Annals of Translational Medicine+1Random chance in very early development
Even with the same PIGL mutations, some children are more severely affected than others. This suggests that random events during early development, or modifying genes, may change how strongly the main genetic cause shows itself.Wiley Online Library+1Unknown additional modifiers
At present, no clear environmental causes (like medicines, infections, toxins) have been proven for CHIME syndrome. However, doctors suspect there may be other genes or small environmental factors that change severity. These are still unknown and are a subject of ongoing research.Annals of Translational Medicine
Symptoms and signs
Different children can have different combinations and severities of symptoms, but the following are common features described in medical reports and rare-disease databases.GARD Information Center+2Orpha+2
Eye colobomas
A coloboma is a missing piece of tissue in the eye, often in the iris (colored part) or retina (back of the eye). Children may have a keyhole-shaped pupil, vision loss in part of the visual field, or more severe vision problems if the retina or optic nerve is involved.Congenital heart defects
Many children have heart problems present at birth, such as a hole between heart chambers (ventricular septal defect) or more complex patterns like tetralogy of Fallot. These can cause poor feeding, fast breathing, blue lips or fingers, and poor weight gain if not treated.Orpha+1Ichthyosiform dermatosis (dry, scaly skin rash)
The skin often shows a migratory “fish-like” rash, with red, scaly, thickened patches that can move from one area to another over time. The rash may be present from birth or early infancy and can cause itching and infection risk if the skin barrier is broken.PMC+1Intellectual disability or global developmental delay
Children may sit, walk, and talk later than other children. They often need support with learning, problem-solving, and daily activities. The degree of difficulty can range from mild to severe.GARD Information Center+1Seizures (epilepsy)
Seizures can occur, sometimes triggered by fever or high environmental temperatures. Types of seizures may vary, and they may need long-term anti-seizure medicine and careful monitoring.GARD Information Center+1Ear anomalies and hearing loss
The external ears may look different in size or shape. Some children have conductive hearing loss, often due to abnormal ear structures or thick skin and scales in the external ear canal. This can delay speech and language if not managed.University of Chicago Genetic Services+1Characteristic facial features
Doctors have described features such as a broad, flat nasal bridge, short philtrum (groove between the nose and upper lip), full lips, wide-set eyes, and sometimes cleft palate or bifid uvula. These features together help doctors suspect the diagnosis.AccessPediatrics+1Feeding difficulties and poor weight gain in infancy
Some babies have trouble sucking, swallowing, or coordinating breathing and feeding. This can lead to poor weight gain and may require special feeding plans or feeding tubes in severe cases.AccessPediatrics+1Abnormal hair, nails, and teeth
As an ectodermal dysplasia, CHIME can cause sparse or fine hair, thick palms and soles, brittle nails, and unusual teeth (widely spaced or missing teeth). These signs reflect the underlying problem in ectoderm development.Orpha+1Movement and balance problems (wide-based gait)
Some children walk with a broad stance and may appear unsteady. This wide-based gait often comes from low muscle tone and brain involvement, and children may need physiotherapy or mobility aids.AccessPediatrics+1Behavioral and learning difficulties
Along with intellectual disability, there may be attention problems, difficulty with social skills, or challenging behaviors, often related to the overall brain involvement and communication difficulties.Kidney or urinary tract anomalies
Some case reports note kidney structure differences or urinary system problems. These can increase the risk of urinary infections and may require nephrology follow-up.AccessPediatrics+1Photosensitivity or eye discomfort
Because of colobomas or other eye problems, bright light may cause discomfort, and children may squint or avoid light. Sunglasses and eye-care support can help.Recurrent infections
Skin breaks from the rash, ear problems, and sometimes heart or kidney issues can all increase the risk of repeated infections (such as ear infections or skin infections). Good hygiene and prompt treatment are important.GARD Information Center+1Overall short stature or growth problems in some children
Some affected individuals are shorter than expected or grow more slowly. This may relate to the underlying genetic condition, feeding difficulties, and frequent illnesses.DoveMed
Diagnostic tests
Because CHIME syndrome affects many parts of the body, diagnosis usually needs a multi-disciplinary team: pediatrician, dermatologist, neurologist, cardiologist, ophthalmologist, ENT specialist, and geneticist. Below are 20 important tests, grouped as you requested.GARD Information Center+2University of Chicago Genetic Services+2
Physical examination tests (bedside, done by looking and touching)
General pediatric physical examination
The doctor carefully looks at the whole child: growth (weight, height, head size), facial shape, body proportions, and any obvious differences in the chest, spine, hands, feet, skin, eyes, ears, and mouth. In CHIME syndrome, this exam often reveals the combination of colobomas, rash, heart murmur, facial features, and ear changes that suggest a single syndrome.Dermatologic (skin) examination
A dermatologist examines the rash’s pattern, thickness, color, and how it moves over time. In neuroectodermal dysplasia CHIME type, the migratory ichthyosiform dermatosis is a strong clue, especially when it begins early in life and is resistant to usual skin treatments.Orpha+1Cardiovascular examination
The doctor listens to the heart (auscultation) for murmurs, extra heart sounds, or signs of heart failure, and checks pulses and blood pressure. In CHIME syndrome, heart murmurs or signs of congenital heart disease often prompt further tests such as echocardiography.Orpha+1Neurologic examination
This includes checking muscle tone, reflexes, coordination, gait, and cranial nerve function (including vision and facial movements). In CHIME syndrome, doctors may find low muscle tone, wide-based gait, and sometimes abnormal eye movements or signs of seizures.ResearchGate+1
Manual / bedside functional tests
Developmental milestone assessment
The clinician uses simple tasks (sitting, standing, walking, using hands, speaking, understanding words) to judge the child’s developmental age. Delays across several areas support the diagnosis of a syndromic condition with global developmental delay such as CHIME.Simple vision testing
Age-appropriate manual tests, such as following a light, fixing on a toy, reading letters or pictures, or matching shapes, help measure how well the child sees. Poor vision or missing fields of view can suggest eye colobomas or other structural problems that match CHIME syndrome.GARD Information Center+1Basic hearing screening
In older children, simple tests like responding to whispered words or tuning fork tests can roughly estimate hearing in each ear. Any sign of reduced hearing leads to more formal audiology testing. In CHIME syndrome, ear anomalies and rash in the ear canal can cause conductive hearing loss.University of Chicago Genetic Services+1
Laboratory and pathological tests
Routine blood tests (full blood count, basic chemistry)
These tests check for anemia, signs of infection, and organ function (such as liver and kidney). While not specific to CHIME syndrome, they help assess general health and guide treatment, especially before surgery for heart or eye problems.Liver function tests and serum enzymes
Doctors may measure liver enzymes and specific markers because CHIME is part of the congenital disorders of glycosylation family, and some CDG conditions show abnormal liver tests or clotting problems.Annals of Translational Medicine+1Serum transferrin isoelectric focusing or other glycosylation screening
In many CDG disorders, this test looks at the sugar patterns on a blood protein called transferrin. Abnormal patterns can suggest a CDG and support the need for targeted genetic testing. PIGL-CDG (CHIME) may show such changes or may need more specialized assays.Annals of Translational Medicine+1Genetic testing: single-gene PIGL sequencing
If the clinical picture strongly suggests CHIME syndrome, targeted DNA testing of the PIGL gene can be done. Finding harmful mutations in both copies of PIGL confirms the diagnosis of neuroectodermal dysplasia, CHIME type.PMC+1Genetic testing: gene panel or exome sequencing
Because the condition is so rare, many centers use panels for ectodermal dysplasia or congenital disorders of glycosylation, or even whole-exome sequencing. These tests can discover PIGL variants even when doctors were not initially thinking of CHIME syndrome.University of Chicago Genetic Services+1Skin biopsy (rarely needed)
In uncertain cases, a small piece of skin may be removed and examined under a microscope. This can show non-specific changes of ichthyosis and help rule out other skin diseases. In CHIME, biopsy is not always needed once genetic testing is available.ResearchGateMetabolic screening tests
Some centers may perform broader metabolic tests (blood and urine) to look for other congenital disorders of glycosylation or metabolic diseases with similar features. This helps make sure the correct diagnosis is reached.Annals of Translational Medicine+1
Electrodiagnostic tests
Electroencephalogram (EEG)
EEG records the brain’s electrical activity. In CHIME syndrome, EEG can show patterns that match epilepsy and can help doctors choose anti-seizure medicines and monitor treatment response.ResearchGate+1Electrocardiogram (ECG)
An ECG records the heart’s electrical signals. It can detect rhythm problems and sometimes suggest underlying structural heart disease, which often co-exists with CHIME syndrome and needs further imaging.Orpha+1Auditory brainstem response (ABR) testing
This test measures how sound signals travel along the hearing nerve to the brainstem. It is especially useful in babies and young children who cannot cooperate with standard hearing tests. In CHIME, ABR can confirm conductive or mixed hearing loss.AccessPediatrics+1
Imaging tests
Echocardiography (heart ultrasound)
Echocardiography uses sound waves to create moving pictures of the heart and its valves and vessels. It is the key test to identify the exact type of congenital heart defect in a child with CHIME syndrome and to plan surgery or other treatment.Orpha+1Brain MRI
Magnetic resonance imaging (MRI) gives detailed pictures of the brain. In CHIME syndrome, MRI may show mild cortical atrophy or other structural changes that help explain seizures and developmental delay and help rule out other conditions.AccessPediatrics+1Ophthalmologic imaging (fundus photography or ocular ultrasound)
Eye specialists may use special cameras or ultrasound to view the inside of the eye. These tests document retinal or optic nerve colobomas and any other eye anomalies, help estimate visual prognosis, and are important for long-term follow-up in children with CHIME syndrome.GARD Information Center+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.
