Zunich-Kaye syndrome is a very rare genetic condition that affects many body systems at the same time. Doctors also call it CHIME syndrome. Children are born with the condition. It mainly affects the skin, eyes, heart, brain, and ears, and can also involve growth and other organs. Wikipedia+1
Zunich–Kaye syndrome, also called CHIME syndrome (Coloboma, Heart defects, Ichthyosiform dermatosis, intellectual disability, Ear anomalies / Epilepsy), is an extremely rare genetic condition. It is an autosomal recessive neuroectodermal dysplasia caused by mutations in the PIGL gene, which is involved in glycosylphosphatidylinositol (GPI) anchor biosynthesis. This leads to abnormal development of skin, brain, eyes, heart, and ears.Ma’ayan Lab+4Orpha+4GARD Information Center+4
Children usually show dry, scaly skin (ichthyosis), eye coloboma, congenital heart disease, intellectual disability, seizures, hearing loss, and characteristic facial features. Only a small number of patients have ever been reported, so almost all treatment is supportive and symptom-based rather than disease-curing. Case reports suggest that oral retinoids such as isotretinoin can improve the ichthyosiform skin lesions, but careful monitoring is needed because of serious side effects.Altmeyers Encyclopedia+3Wikipedia+3MalaCards+3
Zunich-Kaye syndrome follows an autosomal recessive pattern. This means a child gets one changed (mutated) copy of the same gene from each parent. The main gene known so far is called PIGL, which is important for making special “anchor” molecules on the surface of cells. NCBI+1
Because these anchors (called GPI anchors) do not form properly, many proteins cannot attach well to the outside of cells. This can disturb normal development of the skin, nervous system, heart, ears, and other organs in the baby before birth, leading to the features seen in Zunich-Kaye syndrome. ZFIN+1
The condition is extremely rare. Only a small number of patients have been reported worldwide since it was first described in the early 1980s. Most of what we know comes from case reports and small series, so doctors are still learning about the full range of signs and long-term outcomes. AccessPediatrics+1
Other names
Zunich-Kaye syndrome has several other names. These names are used in different books and rare-disease databases, but they all refer to the same main condition. GARD Information Center+1
One common name is CHIME syndrome. CHIME is an English short form made from the first letters of the main features: Coloboma of the eye, Heart defects, Ichthyosiform (fish-like) skin changes, Mental/intellectual disability, and Ear problems or epilepsy (seizures). Wikipedia+1
Another group of names are Zunich neuroectodermal syndrome, Zunich neuroectodermal dysplasia, or neuroectodermal dysplasia CHIME type. “Neuroectodermal” means that it mainly affects tissues that form the brain, spinal cord, skin, and some sense organs in the embryo. AccessPediatrics+1
Databases of rare diseases also use names like “coloboma, congenital heart disease, ichthyosiform dermatosis, intellectual disability, and ear anomalies syndrome” or PIGL-CDG (PIGL-related congenital disorder of glycosylation) to describe the same clinical picture linked to PIGL gene changes. GARD Information Center+1
Types of Zunich-Kaye (CHIME) syndrome
Doctors do not have strict official “types” of Zunich-Kaye syndrome because so few people have been reported. However, experts sometimes group patients in simple clinical ways to help describe the condition. AccessPediatrics+1
One group can be called “classic CHIME phenotype.” These patients show most or all of the features in the CHIME name: eye coloboma, heart defect, skin changes, intellectual disability, and ear anomalies or seizures. Their signs match the original case descriptions very closely. Wikipedia+1
A second group can be thought of as “incomplete or atypical CHIME.” These patients have a confirmed PIGL gene mutation but may miss one big feature, for example they may not have a heart defect, or their skin changes are mild. The overall picture still fits the syndrome, but it is less typical. NCBI+1
A third clinical group might be called “PIGL-CDG with CHIME features.” These patients have PIGL-related congenital disorder of glycosylation and show CHIME-like signs plus extra metabolic or organ problems, because glycosylation problems can affect many proteins and systems. Monarch Initiative+1
Finally, there are patients who show a “CHIME-like phenotype without proven PIGL mutation.” In these children, doctors suspect Zunich-Kaye syndrome based on the typical combination of eye, skin, heart, and developmental problems, but a gene change cannot yet be found, or genetic testing is not available. NCBI+1
Causes and risk factors
Pathogenic PIGL gene variants are the main known cause. A variant means a change in the DNA code that damages how the PIGL protein works. When both copies of the gene are changed, the child develops Zunich-Kaye syndrome. NCBI+1
Autosomal recessive inheritance means that parents usually each carry one silent changed copy of PIGL but are healthy. When two carriers have a baby together, there is a 1 in 4 (25%) chance in each pregnancy that the child will be affected. NCBI+1
Parental carrier status is therefore an important background cause. The more carriers of the same rare variant there are in a family or community, the higher the chance that a child may inherit two changed copies. NCBI+1
Consanguinity (parents being related by blood) increases the chance that both parents carry the same rare PIGL variant. In some reported families with CHIME-like disorders, the parents were related, which supports autosomal recessive inheritance. PubMed+1
De novo PIGL variants may sometimes occur. “De novo” means the gene change appears for the first time in the child, not inherited from either parent. This can still cause disease if both gene copies are affected in different ways. NCBI+1
Defective GPI-anchor biosynthesis is the molecular mechanism. PIGL is part of a multi-step pathway that builds glycosylphosphatidylinositol (GPI) anchors. When this step fails, many cell-surface proteins cannot attach properly, which disrupts cell communication. ZFIN+1
Abnormal cell-surface signaling follows from the GPI-anchor defect. Proteins that should sit on the outside of nerve cells, skin cells, or immune cells may be missing or reduced, leading to problems in brain development, skin structure, and organ formation. ZFIN+1
Disturbed embryonic neuroectoderm development is another level of cause. Neuroectoderm is tissue that forms the nervous system, eyes, and some facial structures. When GPI-anchored proteins do not work, this tissue cannot develop normally, causing colobomas and brain involvement. NCBI+1
Abnormal skin barrier formation happens because skin cells also need GPI-anchored proteins. This leads to ichthyosiform (scaly, dry) patches that may move or change with time, a hallmark of CHIME syndrome. Wikipedia+1
Disordered heart development is another effect. During early pregnancy, the heart is very sensitive to small molecular signals. Faulty cell-surface proteins can disturb these signals and result in structural heart defects such as septal defects. NCBI+1
Abnormal ear and hearing development can occur for similar reasons. The external ear, middle ear bones, and hearing pathways in the brain are influenced by GPI-anchored proteins, so children may have ear shape differences or conductive hearing loss. Wikipedia+1
Brain development problems are central to the cause of intellectual disability and seizures. Incorrect placement of nerve cells, altered wiring, and impaired synapse function may all result from the lack of needed cell-surface proteins. NCBI+1
Genitourinary developmental effects may appear in some patients, such as kidney or urinary tract anomalies, because these organs also rely on complex signaling during embryonic life. NCBI+1
Modifier genes probably influence how severe the condition is. Other genes that affect glycosylation or cell signaling can make the phenotype milder or more severe, which may explain the different clinical pictures seen in reports. Monarch Initiative+1
Population or founder effects might play a role in certain regions or families, where one rare PIGL variant is shared by many related people. This has been seen in other autosomal recessive rare diseases, though data for CHIME itself are limited. Myobase+1
Limited access to genetic testing is not a biological cause but affects diagnosis. In areas without sequencing, some children with PIGL variants may be labeled with other syndromes or remain undiagnosed, which hides the true frequency of the condition. GARD Information Center+1
Random chance in embryonic development also matters. Even with the same gene variants, small random differences in early development can change how strongly different organs are affected, influencing the final clinical picture. NCBI+1
Possible environmental modifiers like infections or poor nutrition during pregnancy have not been clearly linked to CHIME, but in general they can worsen outcomes of genetic disorders, so doctors still encourage healthy pregnancy care. GARD Information Center+1
Under-recognized congenital disorder of glycosylation (CDG) patterns may be part of the cause. PIGL-related CHIME is considered a form of CDG, and this group of conditions is known to have very variable signs, often involving multiple organs. Monarch Initiative+1
Unknown factors almost certainly remain. Because so few cases are known, researchers believe there are still undiscovered gene variants, pathways, and modifiers that help cause or shape Zunich-Kaye syndrome in different children. NCBI+1
Symptoms and clinical features
Eye coloboma is a key sign. A coloboma is a gap or missing piece in part of the eye, such as the iris or retina, that forms before birth. It can affect vision and may make the pupil look like a keyhole or tear-drop shape. Wikipedia+1
Congenital heart defects are common. These can include holes in the walls between chambers (septal defects) or more complex structural heart problems. They may cause a heart murmur, poor feeding, fast breathing, or poor weight gain in the baby. NCBI+1
Ichthyosiform skin changes mean the skin looks very dry, scaly, or rough, like fish scales. In CHIME syndrome, the rash can move or change location (migratory), and it may be more obvious in early childhood, sometimes improving with age. Wikipedia+1
Intellectual disability or global developmental delay is another core feature. Children may sit, walk, or talk later than other children, need extra help in school, and have lifelong learning difficulties, with severity from moderate to severe. Wikipedia+1
Ear anomalies include unusual shape or position of the external ears, and sometimes structural problems in the middle ear. These differences are often noticed at birth and are part of the “E” in CHIME. Wikipedia+1
Hearing loss is often conductive (related to sound conduction through the ear) but can involve the inner ear or nerve pathways. It may cause delayed speech and language development and can add to learning difficulties if not detected and supported. NCBI+1
Epilepsy or seizures may occur in some patients. Seizures are sudden bursts of abnormal electrical activity in the brain and can look like staring spells, stiffness, jerking, or loss of awareness. They often start in childhood and need long-term follow-up. Wikipedia+1
Distinctive facial features can include wide-set eyes, broad nasal bridge, or other subtle differences in facial bones and soft tissues. These features are not harmful themselves but help doctors recognize a pattern together with other signs. NCBI+1
Growth problems such as short stature or poor weight gain can appear. Some children may be smaller than expected for age and family background, partly due to heart disease, feeding difficulties, or general multi-system illness. NCBI+1
Feeding difficulties, especially in infancy, can include poor sucking, trouble coordinating breathing and swallowing, or tiring easily while feeding because of heart or neurologic problems, leading to slow weight gain. NCBI+1
Recurrent infections may occur, particularly ear and respiratory infections. These can be related to structural ear defects, possible immune effects, or aspiration due to feeding or swallowing problems. NCBI+1
Behavioral and communication difficulties are common in children with significant intellectual disability. They may have limited speech, need alternative communication methods, and sometimes show hyperactivity, irritability, or autistic-like features. NCBI+1
Genitourinary anomalies such as kidney malformations or genital differences have been reported in some patients, again reflecting the multi-system nature of the syndrome. These can affect kidney function or urinary flow. NCBI+1
Muscle tone and coordination problems may be present. Some children have low muscle tone (hypotonia), clumsiness, or difficulty with fine motor skills, which can delay walking and self-care skills like feeding or dressing. NCBI+1
General multi-organ involvement means that different combinations of the above features can appear in each child. No two patients look exactly the same, which can make early diagnosis challenging and requires a broad, careful clinical assessment. NCBI+1
Diagnostic tests
Physical examination tests
Full pediatric physical examination is the first and most important test. The doctor carefully checks the whole body, including head shape, face, eyes, ears, chest, abdomen, skin, limbs, and reflexes, to look for the combination of signs that suggests Zunich-Kaye syndrome. NCBI+1
Growth measurement and charting involves recording weight, height, and head size and plotting them on standard growth charts. This helps show whether growth is normal, slow, or falling behind, which often happens in complex genetic syndromes. NCBI+1
Detailed skin examination allows the doctor to see the ichthyosiform (dry, scaly) patches, their pattern, and whether they move or change over time. The look and behavior of the rash can strongly support a CHIME diagnosis. Wikipedia+1
Cardiac examination is done with inspection, palpation, and listening (auscultation) using a stethoscope. The clinician listens for murmurs, extra sounds, or rhythm problems that might indicate a congenital heart defect needing further imaging. NCBI+1
Neurological and developmental examination checks reflexes, muscle tone, strength, coordination, and age-appropriate skills (such as head control, sitting, standing, speech). This helps measure the degree of developmental delay or neurologic involvement. NCBI+1
Manual tests
Developmental screening scales (for example, simple checklists of motor, language, and social skills) are used by doctors or therapists to see which milestones the child has reached and which are delayed. These tools help plan early intervention and therapies. NCBI+1
Vision tracking and fixation tests are simple bedside tests. The examiner moves a bright object and watches whether the baby or child can fix their gaze and follow it. Poor tracking can suggest visual impairment from coloboma or other eye problems. Wikipedia+1
Basic hearing response tests such as making sounds from different sides and watching the child’s head turn help screen for hearing loss. In older children, manual tuning fork tests or simple whispered-voice tests may also be used. NCBI+1
Manual muscle tone and strength assessment involves the doctor gently moving the child’s limbs, feeling resistance, and asking older children to push or pull against the examiner’s hands. This helps detect low tone, weakness, or coordination problems. NCBI+1
Feeding and swallowing assessment by a therapist or clinician uses careful observation during feeding, sometimes with simple bedside tests, to see if the child coughs, chokes, or tires easily, which may signal the need for more detailed studies. NCBI+1
Laboratory and pathological tests
PIGL gene sequencing is the key lab test. A blood sample is sent to a genetics laboratory, where the DNA code of the PIGL gene is read. Finding disease-causing variants in both gene copies confirms the molecular diagnosis of Zunich-Kaye syndrome. NCBI+1
Broader gene panel or exome sequencing may be used when the diagnosis is not clear. These tests look at many genes at once or even all coding genes, increasing the chance of finding a PIGL mutation or ruling out other similar syndromes. NCBI+1
Serum transferrin isoelectric focusing or glycosylation studies can show patterns typical of congenital disorders of glycosylation (CDG). Because PIGL-related CHIME is a form of CDG, abnormal transferrin glycosylation supports this diagnosis. Monarch Initiative+1
Basic blood tests (complete blood count, electrolytes, liver and kidney function) help evaluate overall health, look for anemia or infection, and check liver involvement, which can occur in some glycosylation defects and multisystem syndromes. NCBI+1
Metabolic screening tests (such as lactate, ammonia, amino acids, and organic acids) are sometimes done to rule out other inborn errors of metabolism that can also cause developmental delay, seizures, or failure to thrive. NCBI+1
Histopathology of skin (skin biopsy) is rarely needed but can be performed in unclear cases. Under the microscope, the pathologist may see specific patterns of scaling and abnormalities in the upper layer of the skin, supporting a diagnosis of ichthyosiform dermatosis. Altmeyers Encyclopedia+1
Electrodiagnostic tests
Electroencephalogram (EEG) records the electrical activity of the brain using small electrodes on the scalp. It helps confirm epilepsy, classify seizure type, and guide treatment, which is important in children with CHIME who present with recurrent seizures. NCBI+1
Electrocardiogram (ECG) measures the heart’s electrical signals. It can detect rhythm problems, conduction delays, or strain on the heart related to structural defects, and is part of routine evaluation in children with congenital heart disease. NCBI+1
Imaging tests
Echocardiography (heart ultrasound) uses sound waves to create moving pictures of the heart. It shows the size, shape, pumping action, and any structural defects, such as holes between chambers, valve problems, or abnormal connections in CHIME syndrome patients. NCBI+1
Brain MRI (magnetic resonance imaging) gives detailed images of brain structures without radiation. It can show malformations, delayed myelination, or other abnormalities that help explain seizures, developmental delay, or hypotonia in Zunich-Kaye syndrome. NCBI+1
Ophthalmologic imaging and detailed eye exam include slit-lamp examination, fundoscopy, and sometimes specialized imaging of the retina. These tests define the exact size and location of the coloboma and help predict how much vision may be affected. Wikipedia+1
Renal and abdominal ultrasound can be done to look for kidney or urinary tract malformations and to screen other abdominal organs. This is useful because CHIME syndrome can involve multiple organs beyond the skin, eyes, heart, and brain. NCBI+1
Skeletal imaging (X-rays) may be considered if there are unusual limb, spine, or chest features. X-rays help show bone shape and growth patterns and can rule out additional skeletal dysplasias that might change management. NCBI+1
Non-Pharmacological Treatments (Therapies and Other Approaches)
Intensive skin care with emollients
Thick, fragrance-free emollient creams or ointments help soften dry, scaly ichthyosiform skin. Applied several times daily after bathing, they trap water in the outer skin layer. This reduces cracking, itching, and risk of infection. Regular moisturization can also improve comfort, sleep, and movement because stiff, tight skin becomes more flexible and less painful.Wikipedia+1Keratolytic skin products (with supervision)
Creams with mild keratolytic agents such as urea or lactic acid can gently remove excess scale. They break down the “glue” between dead skin cells, making the surface smoother. Used carefully under dermatology guidance, they can improve skin appearance and allow emollients to work better. Over-use can irritate and must be avoided in babies and young children.Altmeyers EncyclopediaLukewarm bathing and oil baths
Short baths with lukewarm (not hot) water and added bath oil help hydrate the skin and loosen scale. After the bath, patting (not rubbing) the skin dry and applying emollient immediately helps lock in moisture. This simple daily routine is a core, low-risk supportive therapy for ichthyosis-type conditions.Wikipedia+1Gentle skin protection and infection control
Because cracked skin is an easy entry point for bacteria, parents are taught to watch for redness, warmth, or pus and to keep nails short to reduce scratching. Loose cotton clothing and avoiding harsh soaps help protect the skin barrier. Early medical review for suspected skin infection prevents serious complications.JAMA Network+1Early developmental stimulation and special education
Children with CHIME syndrome often have intellectual disability and learning difficulties. Early intervention programs, including physiotherapy, occupational therapy, and speech therapy, support motor, language, and social skills. Structured routines, visual supports, and special education services help each child reach their personal best level of independence.Orpha+2GARD Information Center+2Speech and language therapy
Hearing loss, cleft palate, and neurological problems can delay speech. Speech therapists use play-based exercises, pictures, and sometimes sign language or communication devices to improve understanding and expression. Early therapy makes daily communication easier for the child and family and reduces frustration and behaviour problems.GARD Information Center+1Hearing aids and auditory rehabilitation
Conductive hearing loss from ear anomalies is common. Hearing aids, bone-anchored devices, or other audiology interventions can greatly improve hearing. Consistent use, combined with auditory training, helps language development and interaction. Regular hearing tests are important because hearing can change over time.GARD Information Center+2Global Genes+2Vision support and low-vision aids
Eye colobomas may reduce vision or cause visual field defects. Regular care from an ophthalmologist, plus glasses, low-vision devices, and environmental adaptations (good lighting, large print, high-contrast objects), can help the child function better. Protecting the eyes from dryness and injury is also important.Wikipedia+2Orpha+2Cardiac monitoring and non-surgical heart care
Children with congenital heart defects need regular follow-up with a pediatric cardiologist. Some heart problems can be managed with careful observation, activity guidance, and medications such as diuretics or ACE inhibitors rather than immediate surgery. Monitoring helps decide the safest time and need for interventions.Orpha+1Seizure safety education
If epilepsy is present, families learn seizure first aid: keeping the child safe during seizures, protecting the head, placing the child on their side, and knowing when to call emergency services. At school and home, supervision plans, safe environments, and avoiding seizure triggers (like sleep deprivation) are key non-drug strategies.GARD Information Center+1Nutritional counseling
Some children may have feeding difficulties, growth problems, or increased energy needs due to chronic skin loss and infections. A dietitian can design high-calorie, nutrient-dense meals and, when needed, special formulas. Good nutrition supports immune function, wound healing, and overall development.Orpha+1Physiotherapy for motor skills
Weak muscle tone, joint stiffness, or heart problems can delay walking and other motor milestones. Physiotherapists use stretching, strengthening, and balance exercises in a playful way. Regular therapy improves mobility, prevents contractures, and supports participation in daily activities.Orpha+1Occupational therapy for daily living skills
Occupational therapists help the child learn self-care tasks like dressing, feeding, and using the toilet, adapting tools and environments when needed. They may recommend special grips, seating, or writing aids. Their goal is to maximize independence at home and school.Orpha+1Psychological and family support
Raising a child with a very rare syndrome is stressful. Psychologists and social workers can provide counselling, coping strategies, and help link families to support groups and social services. Emotional support reduces caregiver burnout and improves family quality of life.GARD Information Center+1Infection prevention and hygiene education
Because of skin problems and possible ear or lung issues, careful hygiene (handwashing, skin care, dental care) and up-to-date vaccinations are essential. Families are taught to recognize early signs of respiratory, ear, or skin infections and seek prompt medical care.CheckOrphan+1Individualized education plan (IEP)
Children often need tailored schooling. An IEP sets clear educational goals, support hours, therapies, and exam accommodations. Regular IEP reviews ensure that the plan matches the child’s changing needs and strengths and helps them progress academically and socially.GARD Information Center+1Environmental temperature and humidity control
Very dry or hot environments can worsen ichthyosis. Using a cool, humidified room and avoiding overheating (too many clothes, hot baths) helps reduce skin dryness and fissures. This non-drug approach is simple but important in daily care.Altmeyers EncyclopediaGenetic counselling for the family
Because Zunich–Kaye syndrome is autosomal recessive, parents are usually carriers. Genetic counselling explains recurrence risk in future pregnancies, options for carrier testing of relatives, and possible prenatal or preimplantation diagnosis. This helps families make informed reproductive decisions.Orpha+2CheckOrphan+2Social services and disability benefits support
Many families qualify for disability benefits, transportation support, or home-care programs. Social workers help navigate applications and coordinate care between hospital, school, and community services, reducing financial and practical strain.Global GenesPeer and patient support networks
Because the syndrome is extremely rare, online or international rare-disease communities can be very helpful. Families can share practical tips and emotional support with others facing similar problems, even if they live in different countries.GARD Information Center+1
Drug Treatments (Symptom-Targeted, Evidence-Informed)
Important safety note: Most medicines below are used off-label for CHIME/Zunich–Kaye syndrome and target specific symptoms like skin disease, seizures, or heart problems. Doses are examples from FDA-approved labels for their usual indications, not prescriptions for a specific child. Always follow a specialist’s exact dosing.
Isotretinoin (oral retinoid)
Isotretinoin is a systemic retinoid approved for severe nodular acne; it reduces sebaceous gland activity and normalizes keratinization. FDA labels describe typical dosing at about 0.5–1 mg/kg/day in divided doses with food, for 15–20 weeks, with strict pregnancy prevention due to extreme teratogenicity and many other serious side effects. Case reports suggest it can improve ichthyosiform dermatosis in CHIME, but it requires expert dermatology supervision and frequent lab monitoring.Bionity+2FDA Access Data+2Acitretin (oral retinoid)
Acitretin (Soriatane) is another systemic retinoid approved for severe psoriasis and other keratinization disorders at doses around 25–50 mg/day (about 0.3–0.5 mg/kg/day), adjusted by response. FDA labeling stresses strict avoidance in women of child-bearing potential for at least three years after stopping due to long-lasting teratogenic risk. In theory, acitretin may help severe ichthyosis in CHIME when other treatments fail, but risk–benefit must be carefully weighed.FDA Access Data+2FDA Access Data+2Topical retinoids (tazarotene or similar, off-label)
Topical retinoids can help abnormal scaling by regulating epidermal differentiation. Applied in thin layers to limited areas, they may soften thick plaques. However, they can cause irritation, redness, and photosensitivity, so they are usually used cautiously in small areas and combined with emollients.Altmeyers Encyclopedia+1Topical corticosteroids for inflamed skin
Low-to-moderate potency topical steroids may be used short-term for itchy, inflamed skin areas. They reduce local inflammation and redness by dampening immune signaling. Overuse can thin skin and cause systemic absorption, so they must be used in limited courses, under dermatology guidance.Altmeyers Encyclopedia+1Oral antihistamines
Sedating or non-sedating antihistamines may be used to control itch and improve sleep. They block histamine receptors, reducing itch perception. Doses follow standard pediatric protocols for allergic conditions, and side effects may include drowsiness or, rarely, paradoxical agitation in children.JAMA NetworkBroad-spectrum antibiotics (for secondary skin infections)
Because cracked skin is infection-prone, short antibiotic courses may be needed when bacterial infection is suspected. Drugs like cephalexin or amoxicillin-clavulanate are chosen based on local guidelines and culture results. They work by inhibiting bacterial cell wall synthesis but can cause allergy, diarrhea, or resistance if overused.JAMA Network+1Antiseizure medications: levetiracetam
Levetiracetam is often used for focal and generalized seizures, including pediatric epilepsy. It modulates synaptic neurotransmitter release and stabilizes neuronal excitability. Dose is usually weight-based and titrated slowly to effect. Common side effects include fatigue, irritability, and mood changes. It is useful because it has relatively few interactions.GARD Information Center+1Antiseizure medications: valproic acid
Valproic acid is a broad-spectrum antiepileptic that increases brain GABA levels and affects sodium and calcium channels. It is often effective for generalized seizures but carries risks of liver toxicity, pancreatitis, weight gain, and teratogenicity, so liver function and blood counts must be monitored closely.GARD Information Center+1Other antiepileptic drugs (e.g., lamotrigine, topiramate)
Lamotrigine and topiramate can also be used depending on seizure type. They act mainly by modulating sodium channels and glutamate/GABA balance. Doses are slowly increased to avoid rash (lamotrigine) or cognitive slowing and kidney stones (topiramate). Choice depends on seizure pattern and comorbidities.GARD Information Center+1ACE inhibitors for certain heart defects or heart failure
In children with specific congenital heart diseases leading to heart failure, ACE inhibitors like enalapril may be used to reduce afterload and improve cardiac output by blocking angiotensin-converting enzyme. Side effects can include cough, low blood pressure, and kidney effects, so careful monitoring is needed.Orpha+1Diuretics for heart failure symptoms
Loop or thiazide diuretics help remove excess fluid in congestive heart failure. They act on kidney tubules to increase salt and water excretion, reducing swelling and breathing difficulty. Risks include electrolyte imbalance and dehydration, so pediatric cardiologists adjust doses carefully.Orpha+1Prophylactic antibiotics for recurrent ear infections (selected cases)
For children with frequent ear infections due to structural ear anomalies, low-dose prophylactic antibiotics may occasionally be considered. They reduce infection frequency but must be used cautiously to avoid resistance. ENT specialists decide on duration and need.GARD Information Center+1Topical ear drops (antibiotic +/- steroid)
When ear infections occur, topical antibiotic or antibiotic-steroid combination drops can treat local infection and inflammation. They are applied directly into the ear canal as directed. Overuse can disturb normal ear flora or cause sensitization, so medical supervision is essential.GARD Information Center+1Antiepileptic rescue medicines (e.g., rectal diazepam, intranasal midazolam)
For prolonged seizures, families may be given emergency benzodiazepine preparations. These enhance GABA’s inhibitory effect, helping stop seizures quickly. They must be used exactly as prescribed to avoid excessive sedation or breathing depression and require training and written seizure action plans.GARD Information Center+1Vitamin D and calcium supplements if on long-term retinoids or antiepileptics
Long-term retinoids and some antiepileptics can affect bone health. Vitamin D and calcium supplementation may be recommended to support bone mineralization. Doses depend on age, diet, and lab values. Excessive doses can cause high calcium levels, so monitoring is needed.FDA Access Data+1Proton pump inhibitors or H2 blockers (for reflux or gastric irritation)
If medicines or neurological problems cause reflux, acid-lowering drugs can protect the esophagus and improve comfort. They reduce stomach acid production but, in long-term use, may slightly increase infection or nutrient malabsorption risks, so they are used at the lowest effective dose.JAMA NetworkAnalgesics and antipyretics (paracetamol, ibuprofen)
These drugs relieve pain and fever, improving comfort during infections or after procedures. They work by inhibiting prostaglandin production. Doses are always weight-based in children and must respect maximum daily limits to avoid liver or kidney injury.JAMA NetworkTopical antiseptics for minor skin breaks
Chlorhexidine or povidone-iodine solutions may be used on small, superficial skin wounds to reduce bacterial load. They act by disrupting microbial cell membranes. Overuse can irritate the skin, so they are limited to clearly infected or high-risk areas.Altmeyers EncyclopediaLaxatives or stool softeners when needed
Some medications (like antiepileptics) or limited mobility may cause constipation. Laxatives such as polyethylene glycol work osmotically to draw water into the stool, while stool softeners reduce stool hardness. Adequate hydration and fiber are always encouraged alongside these medicines.JAMA NetworkMultivitamin preparations (if dietary intake is poor)
When eating is limited due to developmental or feeding problems, pediatric multivitamins can help cover basic micronutrient needs. They supply small amounts of many vitamins and minerals, supporting immune function, skin repair, and growth. Doses follow age-appropriate guidelines.CheckOrphan+1
Dietary Molecular Supplements (Supportive Nutrients)
(These are general supportive ideas often used in chronic conditions; they are not disease-specific cures and should only be used if a physician or dietitian agrees.)
Omega-3 fatty acids (fish oil)
Omega-3s (EPA/DHA) are long-chain fatty acids found in fish oil. They have anti-inflammatory effects by modifying eicosanoid and cytokine production. In children with chronic inflammatory skin or heart issues, they may support cardiovascular health and reduce inflammation. Typical pediatric doses are weight-based; excess can increase bleeding tendency or cause stomach upset.Vitamin D
Vitamin D is crucial for bone health, immune function, and possibly skin barrier integrity. It helps the gut absorb calcium and supports normal immune responses. Supplementation is considered if blood levels are low or if sun exposure is limited. Doses follow pediatric guidelines; very high doses can cause high calcium and kidney problems.Vitamin A (with great caution)
Vitamin A is vital for skin and vision, but excess can be toxic, especially when systemic retinoids like isotretinoin or acitretin are used. If the child is not on retinoids and has proven deficiency, a carefully controlled supplement may help skin and eye health. However, any vitamin A use must be closely supervised to avoid toxicity.FDA Access Data+1Zinc
Zinc is important for skin repair, immune function, and taste. Deficiency can cause dermatitis, poor wound healing, and growth failure. Supplementation in deficient children may improve skin integrity and resistance to infection by supporting enzyme systems and cell division. Excess zinc can interfere with copper absorption, so balanced dosing is crucial.Selenium
Selenium is a trace element that supports antioxidant enzymes such as glutathione peroxidase. Adequate selenium may help limit oxidative damage in chronic inflammatory states. However, the therapeutic window is narrow; high doses can cause hair loss, nail changes, and gastrointestinal upset.Probiotics
Probiotic supplements contain live beneficial bacteria that can help balance gut microbiota. A healthier gut ecosystem may support immune regulation and reduce infection risk. Strain-specific evidence exists mainly for general gastrointestinal health, not CHIME itself. Side effects are usually mild but serious infection risk must be considered in very immunocompromised patients.Medium-chain triglyceride (MCT) oil
MCT oil provides easily absorbed calories that do not require complex digestion. It can help children with poor appetite or malabsorption maintain weight and energy. MCTs are rapidly oxidized for energy; too much can cause diarrhea or abdominal discomfort, so dosing starts low.L-carnitine
Carnitine helps transport long-chain fatty acids into mitochondria for energy production. Some children with chronic disease or antiepileptic therapy may have low levels, contributing to fatigue or muscle weakness. Supplementation, if deficiency is documented, may improve energy and endurance, but unnecessary use offers little benefit.B-complex vitamins
B vitamins act as co-factors in many metabolic pathways involved in energy production and DNA synthesis. Deficiency can cause anemia, neuropathy, and fatigue. A balanced B-complex supplement in poor eaters can support general metabolism, but megadoses are rarely needed and may cause side effects.Protein-rich oral nutrition supplements
High-protein, calorie-dense liquid supplements can help children who cannot eat enough solid food. Adequate protein supports wound healing, muscle maintenance, and immune responses. A dietitian calculates the appropriate volume and formula to avoid overfeeding or worsening reflux.
Immunity-Boosting, Regenerative and Stem-Cell–Related Drugs
Intravenous immunoglobulin (IVIG)
IVIG is a purified antibody preparation from donor plasma, used for some immune deficiencies and autoimmune diseases. It can modulate immune responses, neutralize pathogens, and provide temporary passive immunity. In CHIME, IVIG is not standard, but might theoretically be considered if a specific immune defect or recurrent severe infections are documented. It is given by infusion under specialist care due to risk of allergic reactions and kidney effects.Granulocyte colony-stimulating factor (G-CSF)
G-CSF stimulates the bone marrow to produce neutrophils. It is used in some neutropenia syndromes to reduce infection risk. In CHIME, which is primarily a neuroectodermal dysplasia rather than classic marrow failure, routine G-CSF is not typical, but might be considered if significant neutropenia is present. Side effects include bone pain and, rarely, spleen enlargement.Erythropoiesis-stimulating agents (ESAs) in selected anemia
If a child has specific types of chronic anemia, ESAs can stimulate red blood cell production by mimicking erythropoietin. This may reduce transfusion needs but also carries risks of high blood pressure and clotting. Their role in CHIME is unclear and would be highly individualized.Hematopoietic stem cell transplantation (HSCT)
HSCT replaces the patient’s bone marrow with donor stem cells. It is established for some immunodeficiency and metabolic syndromes, but there is no standard evidence for CHIME. Any role would be experimental, aiming to correct underlying GPI-anchor defects if that became technically feasible. HSCT carries major risks, including graft-versus-host disease and severe infections.Gene-therapy approaches (future perspective)
Because CHIME is linked to PIGL mutations, in theory gene therapy might one day correct the underlying defect by delivering a healthy gene copy. At present, no approved gene therapy exists for Zunich–Kaye syndrome. Research in other monogenic disorders suggests that such approaches may be possible in the future but are still experimental and available only in clinical trials.CheckOrphan+1Biologic immunomodulators (case-by-case)
Biologic drugs that target specific inflammatory pathways are used in some severe dermatologic or autoimmune diseases. Examples include monoclonal antibodies against cytokines. For CHIME, there is no specific evidence; in theory, such drugs could be considered if there is severe, treatment-resistant inflammatory skin disease or autoimmunity, but only within specialist centers and possibly research protocols.
Surgical Treatments (Procedures and Reasons)
Corrective surgery for congenital heart defects
If the child has structural heart problems such as septal defects or valve anomalies, pediatric cardiac surgery may be needed. Surgeons repair or reconstruct affected structures to improve blood flow and prevent heart failure or pulmonary hypertension. Timing depends on defect severity and the child’s overall health.Orpha+1Ear reconstruction or canal surgery
Children may have ear malformations affecting hearing and appearance. ENT or plastic surgeons can reconstruct the pinna or ear canal, improving both hearing and self-image. Surgery also helps reduce chronic infections by improving drainage and canal shape.GARD Information Center+2Global Genes+2Cleft palate repair
If a cleft palate is present, surgical closure helps normal speech development, swallowing, and ear health. Surgeons realign and join the palate tissues, usually in early childhood. This reduces nasal regurgitation, improves articulation, and may lower ear infection risk.Bionity+1Ophthalmic surgery for complications of coloboma
While the coloboma itself is often not fully correctable, surgery may be needed for related problems such as cataract, retinal detachment, or eyelid malposition. Procedures aim to protect vision, prevent further damage, and improve eye comfort and alignment.Wikipedia+1Skin surgery or grafting in severe complications
Most skin care is non-surgical, but occasionally severe scarring, contractures, or recurrent infections may require surgical debridement, contracture release, or grafting. The aim is to restore movement, reduce infection risk, and improve quality of life. Dermatologic and plastic surgery teams plan these interventions carefully due to fragile skin.Altmeyers Encyclopedia
Prevention and Risk Reduction
Genetic counselling before future pregnancies
Parents of an affected child should be offered carrier testing and counselling. Understanding the autosomal recessive pattern helps them plan future pregnancies and consider options like prenatal or preimplantation genetic diagnosis where available.Orpha+1Early diagnosis in siblings
If another child in the family shows suspicious signs (ichthyosis, eye coloboma, heart issues), early genetic and clinical evaluation allows quicker supportive care, reducing complications.Up-to-date immunizations
Routine vaccines and additional recommended vaccines where appropriate help reduce infections that can worsen heart or respiratory problems and stress fragile skin.GARD Information Center+1Prompt treatment of skin breaks and infections
Daily skin inspection and early care for cracks or blisters reduce bacterial spread and serious infections such as cellulitis or sepsis.Avoid unnecessary sun and heat exposure
Retinoids and thin, abnormal skin increase sensitivity to sunlight. Protective clothing and sunscreen (if tolerated) can reduce burns and further skin damage.FDA Access Data+1Avoid known seizure triggers
Good sleep routines, avoiding flashing lights (if photosensitive), and prompt treatment of fever may reduce seizure frequency in some children.Regular heart and hearing check-ups
Scheduled follow-ups allow early detection of worsening cardiac function or hearing loss and timely intervention before permanent damage occurs.Orpha+1Balanced nutrition and hydration
Good nutrition strengthens immunity and wound healing and helps avoid growth failure. Ensuring adequate fluids supports skin and circulation.Safe home environment
Adapting the home (no sharp edges, non-slip flooring, supervision near water) helps prevent injuries during seizures or because of visual or coordination difficulties.Avoid pregnancy while on systemic retinoids
If the patient is female and of child-bearing potential, strict contraception is vital during and for a prolonged period after isotretinoin or acitretin use, as these drugs can cause severe birth defects.FDA Access Data+2FDA Access Data+2
When to See Doctors
Parents and caregivers should keep regular appointments with the child’s pediatrician, dermatologist, neurologist, cardiologist, ophthalmologist, and audiologist. Seek urgent medical care if there is:
Sudden breathing difficulty, bluish lips, or signs of heart failure (fast breathing, sweating, poor feeding).Orpha+1
A seizure lasting more than 5 minutes, repeated seizures without recovery, or any seizure with injury or breathing problems.GARD Information Center+1
High fever, spreading redness, pus, or pain in the skin, suggesting serious infection.Altmeyers Encyclopedia
Sudden vision changes, eye pain, or signs of retinal problems.Wikipedia+1
Rapid swelling of the face or tongue, severe drug rash, or breathing difficulty after any medicine (possible allergy).FDA Access Data+1
For non-emergency issues, see doctors for poor growth, feeding problems, sleep difficulties, behaviour worries, or any new symptom that concerns the family.
What to Eat and What to Avoid
Eat: balanced meals with whole grains, fruits, vegetables, and adequate protein (eggs, dairy, fish, legumes) to support growth, skin repair, and immune function.
Eat: healthy fats such as those from fish, nuts (if safe), seeds, and plant oils to provide energy and support cell membranes.
Eat: foods rich in zinc, iron, and B-vitamins (meat, pulses, leafy greens) to help blood, skin, and overall energy.
Eat: sufficient calcium and vitamin-D-containing foods (dairy, fortified products) if tolerated, to support bones, especially if on long-term retinoids or antiepileptics.FDA Access Data+1
Avoid: very salty, heavily processed foods if there are heart issues, as they can worsen fluid retention and blood pressure.Orpha+1
Avoid: excessive simple sugars and sugary drinks, which offer little nutrition and may contribute to weight problems.
Avoid: alcohol completely in adolescents or adults with CHIME, especially if taking retinoids or valproate, because of liver and teratogenic risks.FDA Access Data+2FDA Access Data+2
Avoid: extreme restrictive diets without medical guidance, as they can cause nutrient deficiencies and worsen growth and healing.
Avoid: very spicy or acidic foods close to bedtime if reflux is a problem, as they can irritate the esophagus.JAMA Network
Avoid: vitamin A or other high-dose supplements unless the doctor specifically prescribes them, especially when on retinoid therapy, to prevent toxicity.FDA Access Data+1
A pediatric dietitian should individualize the diet plan based on local foods, cultural habits, and the child’s exact medical status.
Frequently Asked Questions (FAQs)
Is Zunich–Kaye (CHIME) syndrome curable?
At present, there is no cure that corrects the underlying PIGL gene defect. Treatment focuses on controlling symptoms, preventing complications, and supporting development and quality of life through multidisciplinary care.Orpha+2GARD Information Center+2What causes this syndrome?
Zunich–Kaye syndrome is caused by biallelic (two-copy) mutations in the PIGL gene, which is important for making GPI anchors. These anchors help attach certain proteins to cell membranes. When this process fails, many tissues, especially skin and nervous system, develop abnormally.CheckOrphan+1How is it inherited?
It is autosomal recessive. This means both parents usually carry one non-working copy of the gene but are healthy themselves. When both pass the non-working copy to a child, the child is affected. Each pregnancy has a 25% chance of being affected, 50% chance of being a carrier, and 25% chance of inheriting two working copies.Orpha+1How rare is Zunich–Kaye syndrome?
It is extremely rare, with only a handful of cases reported worldwide since the first description in 1983. Many clinicians will never see a case in their entire career, which is why expert centres and case reports are so important.AccessPediatrics+2JAMA Network+2What are the main symptoms?
Typical features include eye colobomas, congenital heart defects, ichthyosiform dermatosis (dry, scaly skin), intellectual disability, ear anomalies, conductive hearing loss, and sometimes epilepsy and facial differences. Not every child will have all features, and severity varies widely.Altmeyers Encyclopedia+3Wikipedia+3Orpha+3Can skin symptoms improve over time?
Some case reports describe improvement of skin lesions with systemic retinoids like isotretinoin, together with intensive emollient care. However, benefits must be balanced against significant side effects and strict pregnancy avoidance in older girls. Skin often remains sensitive and needs lifelong care.FDA Access Data+3Bionity+3Altmeyers Encyclopedia+3Will my child be able to go to school?
Most children with CHIME can attend school with appropriate support, such as special education services, teaching assistants, and accommodations for hearing, vision, and learning difficulties. Early developmental intervention improves school readiness, but expectations should be realistic and individualized.GARD Information Center+1What is the long-term outlook (prognosis)?
Because the condition is so rare, long-term outcomes are not fully known. Some individuals live into adulthood with significant disabilities but stable health when well supported. Outcomes depend on the severity of heart defects, seizure control, infections, and access to comprehensive care.PMC+2ResearchGate+2Can future pregnancies be tested?
If the family’s PIGL mutations are known, prenatal diagnosis or preimplantation genetic testing may be possible in specialized centres. Genetic counsellors help families understand available options, accuracy, and ethical considerations.Orpha+1Are there specific lifestyle restrictions?
Lifestyle is adapted to each child’s abilities and heart/neurological status. In general, safe physical activity is encouraged, but contact sports may be limited if there are vision, bone, or heart concerns. Extra care is needed around water and heights due to seizures or poor coordination.Orpha+2GARD Information Center+2Are vaccines safe in this syndrome?
Routine vaccinations are usually recommended and are important to prevent serious infection, unless there is a specific immune problem or contraindication. The medical team will provide an individualized vaccination plan.GARD Information Center+2Global Genes+2Does diet alone treat the condition?
No diet can cure the genetic defect, but good nutrition supports growth, immunity, and wound healing. A balanced diet, sometimes with supplements, is an important part of overall management but should be combined with medical and therapy care.Orpha+1Is stem cell therapy a standard treatment now?
No. Stem cell or gene-therapy approaches for CHIME are still theoretical or experimental. At present there are no widely accepted, approved stem-cell treatments specifically for Zunich–Kaye syndrome. Any offer of “miracle cures” outside proper research centres should be viewed with extreme caution.CheckOrphan+1Which specialists should be involved?
Care is usually coordinated by a pediatrician or clinical geneticist and often includes a dermatologist, neurologist, cardiologist, ophthalmologist, audiologist, physiotherapist, occupational therapist, speech therapist, and psychologist or social worker. Regular team reviews help align all treatments and goals.Orpha+2GARD Information Center+2Where can families find more information and support?
Reliable information and support can come from national rare-disease organizations, Orphanet, GARD, and specialized genetic centres that have experience with CHIME/Zunich–Kaye syndrome. These groups help connect families, share practical guidance, and provide updates on new research and clinical trials.National Organization for Rare Disorders+3Orpha+3GARD Information Center+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.
