CHIME syndrome is a very rare genetic disease that affects many parts of the body, especially the eyes, heart, skin, brain, and ears. The name “CHIME” comes from the main features: Coloboma (eye defect), Heart defects, Ichthyosiform dermatosis (dry, scaly skin), Mental or intellectual disability, and Ear anomalies or epilepsy.malacards.org
Chime syndrome (also called Zunich neuroectodermal syndrome or CHIME syndrome) is a very rare genetic condition caused by changes in the PIGL gene. It affects many body systems and usually includes eye coloboma, heart defects, severe ichthyosiform (dry, scaly) skin, intellectual disability, ear anomalies, hearing loss and sometimes seizures. There is no single cure or specific “Chime drug”. Treatment is supportive and focuses on skin care, heart care, seizure control, hearing and vision support, and developmental help throughout life. Genetic Diseases Info Center+3Orpha+3malacards.org+3
Doctors describe CHIME syndrome as a type of “neuroectodermal” or “ectodermal dysplasia” disorder. This means it mainly affects tissues that come from the outer layer of the embryo, such as skin, nerves, eyes, and parts of the ear. The condition usually starts at birth or in early childhood and lasts for life.Orpha
CHIME syndrome is autosomal recessive. This means a child needs to receive one faulty copy of the gene from each parent to have the disease. The parents are usually healthy carriers and do not show symptoms. Only a small number of patients have been reported worldwide, so almost everything we know comes from case reports and small studies.dnatesting.uchicago.edu+1
The main known cause is a change (mutation) in the PIGL gene, which is important for making GPI anchors. GPI anchors are small structures that help certain proteins stick to the surface of cells. When PIGL does not work properly, many cell-surface proteins cannot attach correctly, and this leads to problems in skin, brain, eyes, heart, and ears.ScienceDirect+1
Other names
CHIME syndrome has several other names. These names all describe the same basic condition but use different medical words or highlight different features.Genetic Diseases Info Center+1
Common other names include:
Zunich–Kaye syndrome / Zunich neuroectodermal syndrome – named after the doctors who first described it in 1983.Wikipedia+1
Neuroectodermal dysplasia, CHIME type – focuses on the involvement of nerve and skin tissues.Genetic Diseases Info Center+1
PIGL-CDG (congenital disorder of glycosylation due to PIGL deficiency) – used when doctors want to stress that it is a glycosylation disorder caused by PIGL gene mutations.Genetic Diseases Info Center+1
Coloboma–congenital heart disease–ichthyosiform dermatosis–intellectual disability–ear anomalies syndrome – a long descriptive name that spells out the main signs instead of using the acronym.Genetic Diseases Info Center+1
Types
There is no formal “type 1, type 2” classification of CHIME syndrome in major medical databases. All reported patients share a similar basic pattern, but doctors sometimes describe different clinical patterns based on which organs are most affected and how severe the problems are. The “types” below are simple ways to think about these patterns; they are not official separate diseases.Orpha+1
1. Classic CHIME pattern
This pattern includes the full set of CHIME features: eye coloboma, heart defect, migratory ichthyosiform skin rash, moderate to severe intellectual disability, and typical ear changes with hearing loss. Many of the first described patients fit this pattern, so it is often considered the “classic” presentation.dnatesting.uchicago.edu+1
2. CHIME with mainly skin and eye involvement
Some children have very striking skin problems and eye colobomas but milder heart disease or less obvious ear changes. In these patients, the skin rash and scaly patches that move around the body may be the most obvious early signs, leading to dermatology referral first.dermacompass.net+1
3. CHIME with severe neurological involvement
In some cases, seizures (epilepsy), developmental delay, and intellectual disability are very prominent. These children may have more frequent or hard-to-control seizures and may need close neurologic care, even if their heart or ear changes are less severe.Genetic Diseases Info Center+1
4. CHIME with major heart disease
A few children have serious congenital heart defects that require early surgery or intensive cardiology follow-up. In this group, heart problems can strongly affect feeding, growth, and energy level, and may be noticed before the skin or eye signs are fully recognized.malacards.org
5. CHIME with multiple organ and genitourinary malformations
Some reported cases also have kidney or urinary tract malformations, unusual uterine shape in girls, or other organ anomalies. In these children, doctors talk about a multi-system pattern, where problems in several organs appear together with the classic CHIME features.dnatesting.uchicago.edu+1
Causes
The main cause of CHIME syndrome is mutation in the PIGL gene. The 20 points below break this down into detailed causes and mechanisms. They are different steps and risk factors around the same basic problem.ScienceDirect+1
1. Autosomal recessive PIGL gene mutation
CHIME occurs when a child inherits two faulty copies of the PIGL gene, one from each parent. Each parent usually has one normal and one mutated copy, so they are healthy carriers but can pass the mutation to their child.dnatesting.uchicago.edu+1
2. Loss of normal GPI-anchor formation
PIGL helps make glycosylphosphatidylinositol (GPI) anchors, which attach many important proteins to the outside of cells. When PIGL does not work, GPI anchors are not made correctly, so these proteins cannot sit properly on the cell surface.ScienceDirect+1
3. Disrupted cell-to-cell communication in the embryo
Many GPI-anchored proteins act like “signposts” that cells use to talk to one another during early development. When these proteins are missing or misplaced, organs like the eyes, heart, and skin do not form in the usual way.ScienceDirect+1
4. Abnormal eye development leading to coloboma
The eyes are very sensitive to small changes during early growth. Faulty signaling caused by PIGL mutations can stop the normal closing of tissue at the back of the eye, leading to a coloboma (a gap or hole in parts of the eye).malacards.org+1
5. Abnormal heart development
The heart forms from complex folds and fusions of early tissue. When cell-surface proteins are not correctly placed, the heart’s walls or valves can remain open or malformed, causing congenital heart defects seen in CHIME syndrome.malacards.org+1
6. Disturbed skin barrier formation
Skin cells need certain surface proteins to form a smooth, strong barrier. With defective GPI anchors, the upper layer of skin does not mature normally, leading to the migratory ichthyosiform rash, dryness, and scaling.dermacompass.net+1
7. Impact on brain development and wiring
Nervous system cells also use GPI-anchored proteins for migration and connection. When this process fails, brain structure and wiring may be altered, contributing to developmental delay and intellectual disability.ScienceDirect+1
8. Ear structure and hearing pathway disruption
The outer and middle ear rely on correct tissue growth for shape and for sound conduction. PIGL-related defects can change the shape of the ears and the ear canal, and may interfere with hearing pathways, leading to conductive hearing loss.dnatesting.uchicago.edu+1
9. Greater effect in ectoderm-derived tissues
Skin, eyes, parts of the ear, and parts of the nervous system all come from the ectoderm. Because GPI-anchor problems especially affect ectoderm-derived tissues, these areas show many of the most obvious symptoms.Orpha+1
10. Specific PIGL mutation types (missense, frameshift, etc.)
Different families may have different exact changes in PIGL, such as single-letter swaps (missense) or small deletions (frameshift). These different mutations can change how much PIGL activity remains and may slightly affect how severe the condition is.ScienceDirect
11. Carrier parents with no symptoms
Parents with one normal and one faulty PIGL gene usually have enough enzyme activity to make adequate GPI anchors. They do not show disease signs but can have children with CHIME if both pass on the faulty copy. This carrier state is part of the cause pattern.dnatesting.uchicago.edu+1
12. Chance pairing of two carriers
Because the condition is so rare, it usually appears in families only when two carriers have a child together by chance, or in communities where people are more likely to share ancestors and the same rare mutation.Orpha+1
13. Possible effect of consanguinity (related parents)
In some rare genetic diseases, parents who are blood relatives can have a higher chance of carrying the same rare mutation. If this occurs with PIGL, it can increase the risk that their children will inherit two faulty copies.Orpha+1
14. Global disturbance of glycosylation pathways
PIGL is part of a large pathway that adds sugar-based groups to proteins. When one step is broken, the whole chain may be affected, leading to a broader “congenital disorder of glycosylation,” of which CHIME is one form.ScienceDirect+1
15. Secondary effects on immune and inflammatory pathways
Abnormal glycosylation can disturb how immune cells and skin cells respond to injury or infection, which may help explain why the skin rash can flare and migrate and why some children may have recurrent infections.Wiley Online Library+1
16. Effects on bone and facial growth
Disrupted signals in early development can alter skull and facial bone growth, which may cause the characteristic facial shape and dental differences often described in CHIME syndrome.Springer+1
17. Genitourinary developmental error
In some patients, the same developmental pathway errors that affect heart and eyes also affect kidneys, urinary tract, or uterus. These organ malformations are secondary effects of the original PIGL mutation.dnatesting.uchicago.edu+1
18. Brain excitability and seizure tendency
Changes in brain structure and cell-surface receptors can make the brain more likely to produce abnormal electrical activity, leading to epilepsy, which is common in CHIME syndrome.Springer+1
19. Interaction with environmental stress (fever, heat)
Reports suggest that seizures or skin symptoms in CHIME can worsen with fever or high environmental temperatures, showing that environmental stress can interact with the underlying genetic cause.Springer+1
20. Very low overall prevalence (rare mutation)
A final “cause” of how we see the disease pattern is that the PIGL mutations that lead to CHIME are extremely rare in the general population. This explains why only a handful of families worldwide are known to be affected.malacards.org+1
Symptoms
CHIME syndrome affects many body systems, so symptoms can be quite varied. Not every child has every symptom, but many share the main features below.malacards.org+1
1. Eye coloboma
A coloboma is a gap or missing piece in structures of the eye, such as the iris or retina. In CHIME, colobomas are often present in both eyes and may reduce vision, sometimes causing blind spots or poor depth perception.malacards.org+1
2. Congenital heart defect
Children with CHIME often have heart defects like holes between chambers or valve problems present at birth. These defects can cause poor weight gain, fatigue, or breathing difficulties, and may need medical or surgical treatment.malacards.org+1
3. Migratory ichthyosiform skin rash
A very typical sign is a red, scaly skin rash that appears in one area and then moves to another area over time. The skin can look dry and cracked, especially in folds or moving parts like elbows and knees.dermacompass.net+1
4. Chronic ichthyosis (dry, scaly skin)
Even when the active rash settles, the skin often stays dry and scaly, similar to other ichthyosis conditions. This can cause itching, discomfort, and risk of skin infection if the barrier becomes very weak.dermacompass.net+1
5. Intellectual disability
Most children with CHIME have moderate to severe learning and thinking difficulties. They may sit, walk, talk, and learn skills later than other children, and usually need extra educational and daily living support.malacards.org+1
6. Developmental delay
Motor milestones like rolling, crawling, and walking can be delayed. Fine motor skills (like grasping objects) and speech can also be slower to develop, reflecting the effect of the gene change on brain development.Springer+1
7. Ear shape anomalies
The outer ears may look small, low-set, or unusually shaped. Sometimes the ear canals are narrow or partly blocked with flaky skin, which can make hearing problems worse.dnatesting.uchicago.edu+1
8. Hearing loss (often conductive)
Many children have conductive hearing loss, meaning sound cannot travel properly through the outer or middle ear. This may make speech development harder and may require hearing aids or other support.Genetic Diseases Info Center+1
9. Epileptic seizures
Seizures are common and can vary from brief staring spells to more obvious convulsions. They may become more frequent with fever or during adolescence, and usually need treatment with anti-seizure medicine.Springer+1
10. Characteristic facial features
Children often share certain facial traits, such as a broad, flat nasal bridge, wide-spaced eyes (hypertelorism), a short area between nose and upper lip, full lips, and widely spaced teeth. These features help doctors suspect CHIME but do not affect intelligence directly.Springer+1
11. Dental anomalies
Teeth may be widely spaced, square-shaped, or erupt late. These changes can affect chewing and appearance and may need dental and orthodontic care.Springer+1
12. Genitourinary abnormalities
Some patients have kidney or urinary tract problems, such as hydronephrosis (swollen kidney) or unusual uterus shape in girls. These issues can affect urine flow and may lead to infections or kidney function problems.dnatesting.uchicago.edu+1
13. Feeding difficulties and poor weight gain
Feeding can be difficult in infancy due to weak sucking, heart problems, or coordination issues. Some babies may need special feeding techniques or temporary feeding tubes to maintain nutrition.malacards.org+1
14. Recurrent respiratory infections
Some children have frequent chest or upper airway infections, possibly due to structural differences, feeding problems leading to aspiration, or a weaker overall condition. These infections may need repeated medical care.Springer+1
15. Large birth size or abnormal growth pattern
A few reports describe babies who are larger than average at birth or who have unusual growth patterns later. Growth may be influenced by heart disease, feeding problems, and hormonal or metabolic factors.Springer+1
Diagnostic tests
Because CHIME syndrome is very rare and affects many organs, doctors use a mixture of clinical examination, manual tests, laboratory studies, electrodiagnostic tests, and imaging to make and confirm the diagnosis.Orpha+1
Physical examination tests
1. Full physical and growth examination
The doctor checks the child’s height, weight, head size, and body proportions, and looks at skin, face, eyes, chest, abdomen, and limbs. This helps identify patterns like ichthyosis, facial features, and chest or limb anomalies that suggest CHIME syndrome.Springer+1
2. Detailed skin examination
A dermatologist or pediatrician looks closely at the skin rash: its color, scale, and how it moves over time. The migratory, ichthyosiform rash in early life is one of the classic clues to CHIME.dermacompass.net+1
3. Eye examination with light and magnifier
Using a light and magnifying tools, the doctor checks for coloboma of the iris or other visible eye structures. This first simple exam can show obvious defects before more advanced eye tests are done.malacards.org+1
4. Cardiac examination with stethoscope
Listening to the heart with a stethoscope can reveal murmurs or abnormal sounds that point to structural heart disease. This triggers more detailed heart imaging studies.malacards.org+1
Manual (bedside) tests
5. Developmental and neurological bedside exam
The doctor checks muscle tone, reflexes, posture, coordination, and simple tasks for the child’s age. Delays or abnormal findings support the presence of a neurodevelopmental disorder such as CHIME.Springer+1
6. Simple vision checking (fix and follow tests)
In babies and young children, the doctor watches whether the child can fix on a face or object and follow it with their eyes. Poor tracking or strange eye movements may show reduced vision due to coloboma or other eye involvement.malacards.org+1
7. Manual hearing screening (response to sound)
At the bedside, the doctor may clap, speak softly, or use simple tools to see if the child turns toward sound. Weak or absent responses may suggest conductive hearing loss and guide more detailed hearing tests.Genetic Diseases Info Center+1
8. Bedside feeding and swallowing assessment
A clinician watches how the baby sucks, swallows, and breathes during feeding. Poor coordination, choking, or fatigue can be early signs of broader neurological or heart-related problems linked to CHIME.Springer+1
Laboratory and pathological tests
9. Targeted PIGL gene sequencing
Genetic testing that reads the PIGL gene letters can confirm the diagnosis by finding disease-causing mutations on both copies of the gene. This is now considered the key confirmatory test for CHIME.ScienceDirect+1
10. Broader gene panel or exome sequencing
Sometimes doctors order a panel of genes for ichthyosis or neurodevelopmental disorders, or whole exome sequencing, when the diagnosis is not yet clear. This can also pick up PIGL mutations and help diagnose CHIME.dnatesting.uchicago.edu+1
11. Routine blood and metabolic tests
Blood counts, liver and kidney tests, and metabolic screens help rule out other causes of skin, heart, or brain problems. While they may be normal or non-specific in CHIME, they are important to exclude other treatable conditions.Orpha+1
12. Skin biopsy with histology
A small skin sample can be taken and examined under a microscope. In CHIME, biopsies may show abnormal keratinization and other features that support the diagnosis of an ichthyosiform dermatosis related to a genetic disorder.dermacompass.net+1
Electrodiagnostic tests
13. Electroencephalogram (EEG)
EEG records brain electrical activity using electrodes on the scalp. It helps detect abnormal patterns that confirm epilepsy and guide seizure treatment in children with CHIME.Springer+1
14. Electrocardiogram (ECG)
ECG measures electrical activity of the heart. It can show rhythm problems or suggest structural heart disease, helping cardiologists understand how CHIME is affecting the child’s heart.malacards.org+1
15. Brainstem auditory evoked responses (BAER/ABR)
This test uses sound clicks and scalp electrodes to measure how sound signals travel along the hearing nerve and brainstem. It gives an objective measure of hearing in children who cannot yet cooperate with standard hearing tests.Genetic Diseases Info Center+1
16. Nerve conduction studies and EMG (in selected cases)
If there are signs of peripheral nerve problems or unusual muscle weakness, nerve conduction studies and EMG may be done. They measure how fast and how well nerves and muscles work, helping to rule out other neuromuscular diseases.Springer+1
Imaging tests
17. Echocardiogram (heart ultrasound)
An echocardiogram uses sound waves to show the structure and motion of the heart. It is essential to identify and monitor congenital heart defects commonly seen in CHIME syndrome.malacards.org+1
18. Brain MRI
MRI scans give detailed images of the brain and can show structural differences that may help explain seizures or developmental delay in CHIME. Although not always specific, MRI assists in ruling out other causes.Springer+1
19. Eye imaging (ocular ultrasound or optical coherence tomography)
Ophthalmologists may use ultrasound or OCT to look at internal eye structures and better define the extent of coloboma and any related retinal or optic nerve changes, which helps estimate visual prognosis.malacards.org+1
20. Renal and abdominal ultrasound
An ultrasound of kidneys and abdomen can detect genitourinary malformations, such as hydronephrosis, and other organ anomalies that sometimes accompany CHIME syndrome.dnatesting.uchicago.edu+1
Non-pharmacological Treatments
Each of these helps the person live more comfortably and reduce complications. Always plan these together with a specialist team.
Daily Emollient Skin Care
Regular use of thick moisturising creams or ointments (emollients) after bathing keeps the very dry, scaly ichthyosiform skin soft. This reduces cracking, itching, pain and risk of infection. The main purpose is to lock water into the outer skin layer and support the damaged skin barrier. The mechanism is simple: oils and occlusive agents form a thin film on the skin, slow water loss, and improve flexibility. eScholarship+1Keratolytic Creams and Lotions
Keratolytic agents such as urea or lactic acid creams help to gently dissolve thick scales and plaques. The purpose is to smooth the skin surface, improve movement and reduce discomfort. Mechanically and chemically, these agents break down the bonds between dead cells in the outer skin layer so that the scales shed more easily. eScholarship+1Gentle Bathing and Soaking
Short, lukewarm baths or soaks soften the scales and prepare the skin for emollients. The purpose is to reduce tightness and improve penetration of creams. Warm water hydrates the stratum corneum, and when followed quickly by moisturiser, the water is trapped in the skin, improving elasticity and comfort. Skin Therapy LetterAvoiding Heat and Overheating
Children with Chime syndrome and ichthyosis may struggle to sweat normally and can overheat easily; heat can also worsen seizures. The purpose of avoiding heat is to prevent heat exhaustion and seizure triggers. Mechanistically, staying in cool environments and using fans or light clothing helps maintain stable body temperature and reduces stress on the brain and heart. accesspediatrics.mhmedical.com+1Eye Protection and Vision Support
Eye colobomas and other eye problems need early assessment by an eye specialist. Simple steps like tinted glasses, lubrication drops, and protection from bright light help comfort and vision. The purpose is to prevent dryness, injury and further damage. Lubricants replace the tear film and glasses block excessive light and particles that could irritate or injure vulnerable structures. accesspediatrics.mhmedical.com+1Hearing Aids and Audiology Therapy
Ear anomalies and conductive hearing loss are common, so regular hearing tests and fitting of hearing aids can improve communication and learning. The purpose is to maximise the child’s ability to hear speech and environmental sounds. Hearing aids work by amplifying sound and sending clearer signals to the inner ear and brain, supporting language development. accesspediatrics.mhmedical.com+1Early Speech and Language Therapy
Because of hearing loss, intellectual disability and sometimes cleft palate or dental problems, speech can be delayed. Speech therapy focuses on improving understanding, expression and use of alternative communication (like signs or pictures). The mechanism is repeated, structured practice that helps the brain build new language pathways and supports social interaction. Orpha+1Physiotherapy (Physical Therapy)
Children may have poor muscle tone, wide-based gait or delayed motor milestones. Physiotherapy uses exercises, stretching and movement games to strengthen muscles, improve balance and prevent contractures. The mechanism is repeated, targeted movement that trains muscles, joints and the nervous system to work more efficiently and safely. accesspediatrics.mhmedical.com+1Occupational Therapy for Daily Living Skills
Occupational therapists help the child learn self-care skills like dressing, feeding and writing using adapted tools. The purpose is to support independence and participation at home and school. Mechanistically, they break tasks into small steps, add equipment (grips, modified cutlery) and adjust environments so the child can succeed. Genetic Diseases Info CenterSpecial Education and Individualised Learning Plans
Most people with Chime syndrome have moderate to severe intellectual disability, so they benefit from special education, smaller classrooms and personalised teaching. The purpose is to match learning methods to the child’s abilities. Structured routines, visual supports and repetition help the brain store and recall information more effectively. Orpha+1Cardiac Rehabilitation and Activity Planning
After heart surgery or in stable heart disease, controlled physical activity helps build stamina. The purpose is to improve heart and lung function without over-straining them. The mechanism is gradual conditioning: light exercise strengthens cardiac muscle and circulation, while monitoring prevents dangerous strain. accesspediatrics.mhmedical.com+1Nutritional Counselling and Feeding Support
Feeding difficulties can come from poor coordination, cleft palate, or swallowing problems. Dietitians and feeding specialists design textures and feeding techniques that are safe and high in calories. The mechanism is to ensure enough energy, protein, vitamins and fluids for growth and skin repair, while reducing risk of choking or aspiration. accesspediatrics.mhmedical.com+1Psychological and Family Support
Caring for a child with a lifelong rare syndrome is stressful. Counselling and support groups help parents and siblings cope, share experiences and manage anxiety or depression. This works by providing emotional validation, teaching coping skills and building social support, which lowers stress hormones and improves family functioning. Genetic Diseases Info CenterInfection Prevention and Skin Hygiene
Because cracked skin can get infected easily, gentle cleansing, careful nail trimming and quick treatment of small wounds are essential. The purpose is to reduce bacterial load on the skin and stop minor infections turning into serious ones. Clean skin and short nails reduce scratching damage and bacterial entry. eScholarship+1Sun Protection
Fragile, treated or retinoid-exposed skin can be more sensitive to sunlight. Regular use of broad-spectrum sunscreen, hats and protective clothing prevents burning and long-term skin damage. The mechanism is blocking or absorbing ultraviolet radiation before it injures skin cells and DNA. jaad.org+1Orthopaedic Supports and Bracing
Some children have foot deformities (for example clubfoot) or joint problems. Orthopaedic supports such as braces or special shoes help align joints and improve walking. Mechanistically, they redistribute weight, stabilise joints and reduce abnormal pressure on bones and ligaments. accesspediatrics.mhmedical.comCleft Palate and Dental Supportive Care
Where there is cleft palate or abnormal dentition, early dental and orthodontic care helps with chewing, speaking and appearance. Special plates or orthodontic appliances guide growth. The mechanism is gradual realignment of teeth and jaw bones and improved seal of the palate for speech and feeding. accesspediatrics.mhmedical.comSeizure Triggers Management (Sleep, Fever, Lights)
Good sleep hygiene, prompt fever control and avoiding flashing lights or other known seizure triggers reduce seizure frequency. The purpose is to stabilise the brain’s electrical activity. Stable sleep patterns and controlled fevers reduce sudden changes in brain excitability that can provoke seizures. accesspediatrics.mhmedical.com+1Genetic Counselling for Family Planning
Because Chime syndrome is autosomal recessive, parents are usually carriers. Genetic counselling helps families understand recurrence risk and discuss options like carrier testing or prenatal diagnosis in future pregnancies. The mechanism is information plus emotional support, helping informed choices. ScienceDirect+1Care Coordination in a Multidisciplinary Clinic
A coordinated team (dermatology, neurology, cardiology, ENT, ophthalmology, genetics, rehab and psychology) improves outcomes. The purpose is to avoid gaps and conflicting treatments. Regular team reviews allow shared decisions, safer medication use and quicker reaction to new problems. UChicago Genetic Services+1
Drug Treatments
Very important: There is no drug officially approved specifically for “Chime syndrome”. Medicines are used to treat its individual problems (skin disease, seizures, heart disease, infections, etc.). All doses below are general label information from FDA prescribing documents for other conditions, not personal medical advice. A specialist must set dose and timing for each patient. FDA Access Data+3Dove Medical Press+3FDA Access Data+3
To stay within space, I will describe 10 of the most important medicine groups used in practice:
Acitretin (Systemic Retinoid for Severe Ichthyosis)
Acitretin is an oral retinoid approved for severe psoriasis, but often used off-label for severe congenital ichthyosis when topical care is not enough. It reduces scaling and thick skin, improves movement and comfort. It works by normalising keratinisation and thinning the thick outer skin layer. Dosing in labels for psoriasis is weight-based (for example around 25–50 mg/day in adults), but in children and ichthyosis lower doses are usually used and must be set by a dermatologist. Common side effects include dry lips, dry eyes, hair thinning and raised liver enzymes; it is strongly teratogenic and absolutely unsafe in pregnancy. FDA Access Data+3eScholarship+3Dove Medical Press+3Isotretinoin (Another Systemic Retinoid)
Isotretinoin is approved for severe nodular acne but is sometimes used off-label at low doses for very severe ichthyosis when the benefits outweigh risks. It reduces scale thickness and itch. The mechanism is similar to acitretin: it influences skin cell growth and reduces thickening of the stratum corneum. Labelled doses for acne are typically about 0.4–1 mg/kg/day for limited months, but dosing in ichthyosis is individual and carefully monitored. Side effects include dry skin and mucosa, liver changes, high lipids and very serious birth defects if taken during pregnancy, so strict pregnancy prevention programs like iPLEDGE are required. ResearchGate+2FDA Access Data+2Topical Retinoids (e.g., Tretinoin) and Combination Creams
Topical retinoids and combination creams (for example containing tretinoin, keratolytics and other agents) may be used on limited areas of thick skin. Their purpose is to smooth local plaques and reduce roughness without systemic exposure. They act by speeding up skin cell turnover and loosening compacted scale. Side effects are mainly local: irritation, redness and sun sensitivity. PMC+2jaad.org+2Ixekizumab (IL-17A Inhibitor – Case Report in Chime)
Ixekizumab is a monoclonal antibody approved for conditions like plaque psoriasis and psoriatic arthritis. Recently, a case report showed that a child with Chime syndrome and severe ichthyosiform dermatosis, who failed many topical therapies and dupilumab, improved significantly on ixekizumab. The drug blocks interleukin-17A, a key inflammatory signal in some skin diseases. Standard psoriatic dosing is 160 mg at week 0 then 80 mg every few weeks, adjusted for age and weight; in Chime this would be specialised off-label use. Side effects include increased risk of infections, injection-site reactions and possible inflammatory bowel disease flares. PubMed+2FDA Access Data+2Levetiracetam (Seizure Control)
Levetiracetam is a broad-spectrum antiseizure medicine. In Chime syndrome it may be used to control seizures that often start in childhood. It works by modulating synaptic neurotransmitter release and lowering neuronal excitability. FDA labels show weight-based dosing that is slowly increased over days, with doses divided twice daily. The exact dose depends on age, kidney function and seizure type. Side effects can include tiredness, dizziness and behavioural changes like irritability or mood swings. FDA Access Data+3accesspediatrics.mhmedical.com+3FDA Access Data+3Other Anti-Seizure Medicines (e.g., Valproate, Carbamazepine)
When levetiracetam alone is not enough, other antiseizure drugs may be added. Their purpose is to reduce seizure number and severity, protecting the brain and improving development. Each works through different mechanisms, such as enhancing inhibitory GABA pathways or blocking sodium channels. Dosing is always started low and slowly increased, with close monitoring for liver problems, blood cell changes or skin reactions depending on the drug. accesspediatrics.mhmedical.com+1Heart Failure and Cardiac Medicines (e.g., ACE Inhibitors, ARBs, Diuretics)
Children with repaired or unrepaired congenital heart defects may need standard heart medicines like ACE inhibitors or ARBs (such as losartan), beta-blockers or diuretics. These drugs lower blood pressure, reduce strain on the heart or remove excess fluid. For example, losartan blocks angiotensin II type 1 receptors, relaxing blood vessels and reducing afterload. Label doses are weight-based and adjusted by a cardiologist. Side effects can include low blood pressure, kidney function changes, electrolyte abnormalities and, for drugs acting on the renin–angiotensin system, fetal toxicity during pregnancy. FDA Access Data+3accesspediatrics.mhmedical.com+3FDA Access Data+3Topical Antibiotics and Antiseptics for Skin Infection
Because of leaking and cracked skin, local infections are common. Short courses of topical antibiotics or antiseptic washes can treat minor infections and prevent deeper spread. They work by killing or slowing bacteria on the skin surface. Overuse is avoided to reduce resistance; side effects are usually limited to irritation or allergy at the application site. eScholarship+1Systemic Antibiotics for Serious Infections
If a skin or chest infection becomes severe, systemic antibiotics by mouth or injection may be needed. The purpose is rapid control of spreading bacterial infection that could trigger sepsis or worsen heart and lung function. Antibiotics act by targeting bacterial cell walls, protein synthesis or DNA replication, depending on class. Doses follow standard paediatric infection guidelines and can cause side effects like diarrhoea, allergic reactions or changes in gut flora. MSD Manuals+1Supportive Medicines (Analgesics, Antipyretics, Eye and Nose Drops)
Simple medicines like paracetamol for pain and fever, lubricating eye drops, and saline nasal sprays are often used. Their purposes are comfort, fever control (important because fever can trigger seizures) and moisture for dry mucosa. Mechanisms vary: paracetamol acts centrally to reduce pain and fever, while lubricating drops physically coat and protect the eye surface. Side effects are usually mild when used at recommended doses, but overdosing analgesics can be dangerous. accesspediatrics.mhmedical.com+1
Because of your word limit request, I have focused on 10 high-yield medicine groups. In real care, the team may use several other standard medicines, always tailored to the individual child.
Dietary Molecular Supplements
Supplements should never replace medical treatment and should only be used under medical supervision, especially with retinoid therapy, to avoid overdose.
Omega-3 Fatty Acids (Fish Oil)
Omega-3 fatty acids support heart health, may reduce inflammation and can help dry skin and joints feel more comfortable. The mechanism is partial replacement of inflammatory fatty acids in cell membranes with more anti-inflammatory ones, changing inflammatory mediator production. Dosing is usually weight-based and should respect safe daily limits to avoid bleeding risk or stomach upset. Dove Medical PressVitamin D
Many children with chronic illness and limited sun exposure have low vitamin D. Replacement supports bone health, immunity and muscle function. Vitamin D works like a hormone, helping the gut absorb calcium and phosphorus and supporting normal bone mineralisation. Dose is based on blood levels; too much can cause high calcium, nausea and kidney problems. Dove Medical Press+1Zinc
Zinc is important for skin repair, immune function and wound healing. In a child with recurrent infections and fragile skin, correcting low zinc may help healing and resistance to infection. Mechanistically, zinc is a co-factor for many enzymes involved in DNA replication and cell division. Excess zinc can cause nausea, interfere with copper absorption and upset the stomach, so dosing must be monitored. Dove Medical PressBiotin (Vitamin B7)
Biotin plays a role in skin, hair and nail health and in energy metabolism. In some genetic skin and hair disorders, biotin supplementation improves symptoms. It acts as a co-enzyme in carboxylation reactions in cell metabolism. Usual supplements are in microgram doses; high doses are generally well tolerated but can interfere with some lab tests, so doctors should know about its use. Dove Medical PressVitamin E
Vitamin E is an antioxidant that protects cell membranes from oxidative damage. In chronic inflammatory skin disease, replacing deficiency may support barrier function and comfort. It stabilises cell membranes by trapping free radicals in lipid layers. High doses, however, can increase bleeding risk and interact with anticoagulant medicines. Dove Medical PressProbiotics
Probiotics are beneficial bacteria given as capsules or yoghurt drinks. They may help gut health, reduce antibiotic-associated diarrhoea and modulate immune responses. The mechanism involves competition with harmful bacteria and production of helpful metabolites in the intestine. Strain and dose matter; evidence is still developing, and some very immunocompromised patients may not be suitable. Dove Medical PressMultivitamin with Minerals
Because feeding can be difficult, a balanced multivitamin–mineral preparation can fill gaps in micronutrient intake. The purpose is to prevent multiple small deficiencies that can worsen fatigue, immunity or skin repair. Mechanistically, it ensures enzymatic systems have needed cofactors. Doses should not exceed recommended daily allowances unless a doctor identifies a specific deficiency. Dove Medical PressProtein Supplements (e.g., Whey Protein)
If oral intake is low and growth is poor, additional protein supplements may be used under dietitian guidance. Protein provides amino acids needed to build skin, muscle and antibodies. In practice, powders or high-protein drinks are added to meals; excessive protein without enough water or in kidney disease can be harmful, so monitoring is needed. Dove Medical PressMedium-Chain Triglyceride (MCT) Oil
MCT oil is a form of fat that is easily absorbed and quickly used for energy. For children with high energy needs and poor appetite, MCT can boost calorie intake in small volumes. It is absorbed directly into the portal circulation, requiring less bile. Too much can cause stomach discomfort or diarrhoea, so dosing starts low. Dove Medical PressIron (Only if Deficient)
If blood tests show iron deficiency anaemia from poor intake or chronic illness, iron supplements may be needed. Iron is essential for haemoglobin and oxygen transport. Oral iron works slowly over weeks by replenishing body stores, but excess iron causes stomach pain, constipation and, in large overdose, poisoning. So it should only be used under medical supervision with lab monitoring. Dove Medical Press
Immunity-Booster / Regenerative / Stem-Cell–Related Drugs
At present, there are no standard “stem cell drugs” or immune-boosting drugs approved specifically for Chime syndrome. The ideas below describe possible or experimental directions rather than routine treatments.
Standard Childhood Vaccinations
The simplest and most powerful “immune booster” is keeping all standard vaccines up to date. Vaccines train the immune system to recognise specific germs and respond faster, reducing severe infections that fragile patients may not tolerate well. They work by safely exposing the immune system to antigens so it can make memory cells. Genetic Diseases Info CenterImmunoglobulin Replacement (in Proven Antibody Deficiency)
If tests showed a true antibody deficiency (which is not typical for all Chime patients but possible in complex cases), intravenous or subcutaneous immunoglobulin might be used. It provides pooled antibodies from donors, offering passive protection while the patient’s own immune system is weak. This is only used when clearly indicated and monitored in hospital. Dove Medical PressHaematopoietic Stem Cell Transplantation (Very Experimental Idea)
In some genetic immune or skin diseases, bone-marrow or stem-cell transplants have been used to replace defective cells. For Chime syndrome, this approach is not established, but in theory, correcting the underlying glycosylation defect in blood-forming cells might change disease expression. The procedure replaces diseased bone marrow with donor stem cells but carries risks like graft-versus-host disease and serious infection. Dove Medical PressMesenchymal Stem Cell Therapy (Research Stage)
Mesenchymal stem cells are being studied for inflammatory and autoimmune conditions because they release anti-inflammatory and tissue-repairing factors. In Chime, such treatment would be purely experimental and only in research studies. The proposed mechanism is modulation of immune cell activity and support of tissue repair, but safety and benefit are not proven here. Dove Medical PressTargeted Biologic Therapies (e.g., Ixekizumab as Above)
Biologic drugs that target specific inflammatory pathways, like IL-17A blockers, can sometimes be viewed as “immune modulators” rather than simple suppressors. In the reported Chime case, ixekizumab reduced skin inflammation and scaling when other therapies failed, showing that precise immune pathway targeting may partly “reset” skin function. But these are strong drugs with infection risks and must be used only by specialists. PubMed+1Future Gene- or Enzyme-Targeted Therapies
Because Chime syndrome is linked to PIGL gene mutations and glycosylphosphatidylinositol (GPI) biosynthesis defects, future therapies might aim at correcting or bypassing this pathway. Ideas include gene therapy or small molecules that improve residual enzyme function. These options are still theoretical and in research, not available for routine care. ScienceDirect+1
Surgeries (Main Types – Procedures and Reasons)
Congenital Heart Defect Repair
Open-heart surgery or catheter-based procedures may be needed to correct defects like ventricular septal defect or tetralogy of Fallot in early life. Surgeons close holes, widen narrowed vessels or re-shape heart structures so blood can flow normally. The reason is to prevent heart failure, poor growth and low oxygen levels. accesspediatrics.mhmedical.com+1Eye Surgery for Coloboma-Related Complications
Some colobomas are observed, but surgery may be required to repair associated retinal detachments or to protect exposed eye structures. The procedure carefully reattaches retina or closes gaps where possible. The reason is to preserve as much useful vision as possible and prevent further damage. accesspediatrics.mhmedical.com+1Cleft Palate and Craniofacial Surgery
If the child has cleft palate or significant facial anomalies, specialised craniofacial surgery can close the palate and improve structure. Surgeons reposition bone and soft tissue to restore separation between mouth and nose. The reason is to improve feeding, speech development and ear health and reduce infections. accesspediatrics.mhmedical.com+1Ear Surgery, Ventilation Tubes or Hearing Implant
For recurrent middle-ear infections or structural ear problems, surgeons may insert ventilation tubes or perform more complex reconstruction. In some cases, cochlear implants are considered. These procedures aim to improve sound conduction to the inner ear, reduce infections and maximise hearing potential. accesspediatrics.mhmedical.com+1Orthopaedic Surgery for Foot or Skeletal Deformities
Clubfoot or significant toe and bone deformities may need operation if bracing is not enough. Orthopaedic surgeons cut and reposition bone and soft tissue to align feet or limbs. The reason is to allow more comfortable walking, reduce pain and prevent early joint damage. accesspediatrics.mhmedical.com
Prevention
Because Chime syndrome is genetic, we cannot fully “prevent” it once the gene changes are present. However, we can reduce complications and recurrence in families:
Genetic counselling before future pregnancies. ScienceDirect+1
Carrier testing of parents and possibly older siblings where appropriate. ScienceDirect
Discussing options for prenatal or pre-implantation genetic diagnosis in high-risk couples. ScienceDirect
Keeping all vaccinations up to date to cut infection risk. Genetic Diseases Info Center
Strict daily skin care to prevent cracking and infection. eScholarship+1
Rapid treatment of fevers and infections to avoid seizures and heart stress. accesspediatrics.mhmedical.com+1
Regular cardiology, neurology, dermatology, ENT and ophthalmology check-ups. UChicago Genetic Services+1
Safe home environment to prevent falls and injuries (especially with seizures or poor vision). accesspediatrics.mhmedical.com
Adequate nutrition and hydration to support growth and skin repair. Dove Medical Press
Emotional and social support for the family to prevent burnout and missed care. Genetic Diseases Info Center
When to See Doctors
Families should keep regular planned appointments with their child’s care team. Urgent medical review is needed if there is:
New or worsening seizures, prolonged seizures, or seizures with breathing problems. accesspediatrics.mhmedical.com+1
Signs of heart failure such as fast breathing, sweating with feeds, blue lips or fingers, or very poor weight gain. accesspediatrics.mhmedical.com
High fever, spreading skin redness, pus-filled lesions or signs of sepsis (extreme sleepiness, fast heartbeat, cold hands and feet). eScholarship+1
Sudden change in vision, severe eye pain, or suspected retinal detachment (flashes, curtain over vision). accesspediatrics.mhmedical.com+1
Severe vomiting, poor feeding or dehydration. Dove Medical Press
Even for non-urgent problems like dry skin flare-ups or behavioural changes, contacting the specialist team early often prevents bigger complications.
What to Eat and What to Avoid
There is no special “Chime diet,” but some patterns support skin, heart and overall health:
Eat: balanced meals with enough calories and protein (meat, fish, eggs, beans, dairy) to support growth, skin repair and immune function.
Eat: foods rich in healthy fats (olive oil, nuts, seeds, avocado, oily fish) to support skin moisture and heart health.
Eat: colourful fruits and vegetables for vitamins, antioxidants and fibre that support immunity and gut health.
Eat: whole grains (oats, brown rice, whole-wheat bread) for steady energy and micronutrients. Dove Medical Press
Eat: enough fluids (water, soups, oral rehydration) to compensate for water loss through damaged skin and reduce constipation.
Avoid: very salty, highly processed foods that can worsen blood pressure and heart strain.
Avoid: very high sugar drinks and snacks that add calories but few nutrients and can worsen weight or dental problems.
Avoid: extremely spicy or acidic foods if they cause stomach upset or reflux in a child with poor feeding.
Avoid: self-supplementing high doses of vitamin A or retinoid-like supplements while on retinoid medicines, because this may cause toxicity. eScholarship+1
Avoid: crash diets or very restricted diets unless a doctor or dietitian designs them, because malnutrition will worsen skin, immunity and healing. Dove Medical Press
Frequently Asked Questions
Is there a cure for Chime syndrome?
Right now there is no cure that reverses the genetic change in PIGL. Treatment focuses on managing each problem—skin, heart, seizures, hearing, vision and development—to give the best possible quality of life. ScienceDirect+1How rare is Chime syndrome?
Chime syndrome is extremely rare, with fewer than one in a million people affected worldwide. Most information comes from single case reports and small case series. Orpha+1What causes Chime syndrome?
Chime syndrome is usually caused by mutations in the PIGL gene, which is involved in making GPI anchors—molecules that help attach certain proteins to cell surfaces. When this pathway is disturbed, many organs, including skin, brain, heart and ears, are affected. ScienceDirect+1Is Chime syndrome inherited?
Yes. It is inherited in an autosomal recessive pattern. This usually means both parents are healthy carriers of one non-working PIGL gene and one normal gene, and the child inherits the non-working copy from both parents. malacards.org+1Will every child with Chime syndrome have the same symptoms?
No. Even with the same genetic change, severity can vary. Most children have eye, skin, heart, hearing and developmental problems, but the exact combination and severity differ from person to person. Orpha+1Can children with Chime syndrome go to school?
Many children can attend school, often in special or inclusive classes, with extra support for learning, hearing and communication. The exact level of schooling depends on each child’s abilities and health. Genetic Diseases Info CenterHow is the skin disease treated?
The skin is treated first with daily bathing, emollients and keratolytic creams. In severe cases, systemic retinoids like acitretin or isotretinoin, or newer biologic drugs like ixekizumab (off-label), may be considered by dermatologists with close monitoring. eScholarship+2Dove Medical Press+2Are retinoid drugs safe?
Retinoids can be very helpful but have serious side effects, especially birth defects if taken during pregnancy. Liver function, blood fats and bone health must be monitored regularly. Doctors use the lowest dose that works and follow strict pregnancy prevention programs for females of child-bearing potential. FDA Access Data+3FDA Access Data+3FDA Access Data+3Do all patients need heart surgery?
Not always. Some heart defects are mild and mainly watched, while others are severe and require early surgery. Decisions depend on the type of defect, symptoms and test results from echocardiography and cardiology review. accesspediatrics.mhmedical.com+1Will seizures last for life?
Many patients will have long-term seizure risk, but good control is often possible with antiseizure medicines and trigger management. Some may see improvement as they grow. Regular neurology follow-up is essential. accesspediatrics.mhmedical.com+1Can Chime syndrome affect life expectancy?
Life expectancy can be reduced, especially if serious heart disease, infections or uncontrolled seizures occur. However, with early diagnosis, modern heart surgery, seizure control and careful skin and infection management, some individuals can live into adulthood. Exact numbers are not well known because the condition is so rare. PMC+1Should families join a rare disease registry or support group?
Yes, if available. Registries and support groups connect families, help share practical tips and may give access to new research and clinical trials. They also help researchers understand the condition better. Genetic Diseases Info Center+1What tests are needed to confirm Chime syndrome?
Diagnosis is based on clinical features plus genetic testing that shows biallelic pathogenic variants in the PIGL gene. Doctors may also do brain imaging, heart ultrasound, eye exams and hearing tests to map all organ involvement. ScienceDirect+2monarchinitiative.org+2Can future pregnancies be tested?
If the parents’ PIGL variants are known, prenatal testing (for example chorionic villus sampling) or pre-implantation genetic testing during IVF can be considered to see if a fetus or embryo is affected. These are complex decisions that need genetic counselling. ScienceDirect+1What is the most important thing families can do day-to-day?
Consistent daily care—skin care, medicines exactly as prescribed, regular follow-ups, good nutrition and a safe, loving environment—makes the biggest difference. Small, repeated actions protect the child’s health and support development over the long term. eScholarship+2Dove Medical Press+2
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.
