Cognitive Impairment – Coarse Facies – Heart Defects – Obesity – Pulmonary Involvement – Short Stature – Skeletal Dysplasia Syndrome

Cognitive impairment – coarse facies – heart defects – obesity – pulmonary involvement – short stature – skeletal dysplasia syndrome is a very rare genetic disease. Doctors also call it CHOPS syndrome. It affects many parts of the body from birth, including the brain, face, heart, lungs, bones, height, and weight. Children usually have learning problems, slow development, and special facial and bone features.

Cognitive impairment-coarse facies-heart defects-obesity-pulmonary involvement-short stature-skeletal dysplasia syndrome is usually called CHOPS syndrome. It is an ultra-rare genetic condition present from birth that affects brain development, face shape, heart, lungs, bones, growth, and body weight.

CHOPS syndrome is caused by changes (variants) in the AFF4 gene. AFF4 helps control how many other genes are turned on during early development, so a fault in this gene can disturb growth in many organs at the same time. The condition usually follows an autosomal dominant inheritance pattern.

This condition is caused by changes (mutations) in a gene called AFF4. This gene helps control how other genes are turned on and off during early growth in the womb. When AFF4 does not work in the normal way, many organs do not develop in the usual pattern, which leads to the signs of CHOPS syndrome.

CHOPS syndrome is congenital, which means it is present at birth. It is also a multiple-malformation disorder, because it affects several body systems at the same time, such as the skeleton, heart, lungs, and nervous system. Only a small number of patients have been reported in the medical literature, so doctors are still learning about this condition.

Other names

Doctors and scientists use several names for this syndrome. All of them describe the same basic condition.

1. CHOPS syndrome – This is the short name. Each letter stands for a main feature: Cognitive impairment, Heart defects, Obesity, Pulmonary (lung) involvement, and Short stature with skeletal changes.

2. Cognitive impairment, coarse facies, heart defects, obesity, pulmonary involvement, short stature, and skeletal dysplasia – This is the long, descriptive name often used in medical databases. It lists the main problems seen in patients.

3. Cognitive impairment-coarse facies-heart defects-obesity-pulmonary involvement-short stature-skeletal dysplasia syndrome – This is a slightly different way of writing the same long name, using dashes instead of commas.

4. CHOPS (AFF4-related) syndrome – Some authors add the gene name AFF4 to show that this is the specific genetic form linked to AFF4 mutations.

Types

There are no official medical “subtypes” of CHOPS syndrome yet. However, doctors sometimes describe patients by how strong the symptoms are or which organs are most affected.

• Classic CHOPS pattern – clear problems in learning, face, heart, lungs, growth, and bones, similar to the first reported patients.

• Mild or attenuated CHOPS – the same basic features but in a softer way, such as milder learning problems or fewer heart or lung issues.

• Severe early-onset CHOPS – strong breathing, heart, and feeding problems in early life, sometimes needing intensive care.

These “types” are clinical patterns only, not separate genetic diseases. They help doctors talk about how serious the condition is in each child.

Causes

1. AFF4 gene mutation (main cause)
   The key cause of this syndrome is a harmful change (mutation) in the AFF4 gene. This mutation changes how the AFF4 protein works and leads directly to the signs of CHOPS syndrome.

2. Gain-of-function effect in AFF4
   Research shows that CHOPS syndrome is linked to gain-of-function mutations. This means the AFF4 protein becomes too active or lasts too long, which disturbs normal gene control during development.

3. Problems in transcription control
   AFF4 is part of a complex that controls transcription, the process of copying DNA into RNA so proteins can be made. When AFF4 does not work in a normal way, many genes are switched on or off at the wrong time, harming organ growth.

4. SEC (super elongation complex) dysfunction
   AFF4 is a core part of the super elongation complex (SEC). Abnormal SEC activity in CHOPS syndrome changes how long RNA polymerase stays on genes, which disrupts normal tissue formation and leads to the body changes seen in patients.

5. Interaction problems with cohesin pathway
   Studies show that AFF4 and the cohesin system interact. Both CHOPS syndrome and some Cornelia de Lange syndrome cases seem to involve disturbed transcription due to changes in these pathways, which affects growth and development.

6. Abnormal bone and cartilage development
   Because AFF4 helps control genes for skeleton formation, its mutation leads to skeletal dysplasia, such as short bones and abnormal vertebrae. This disturbed bone growth is a direct cause of short stature and bone problems.

7. Abnormal heart development (cardiac morphogenesis)
   During fetal life, heart structures such as the septum and ductus arteriosus must form and close correctly. Disordered gene control from AFF4 mutations can disturb these steps and cause heart defects.

8. Disordered lung and airway development
   AFF4-related gene changes can affect the airways and lung tissue. This can lead to airway weakness (laryngeal or tracheal malacia) and chronic lung disease, which are part of the CHOPS picture.

9. Brain development disruption
   The brain needs very precise gene control during pregnancy. When AFF4 is over-active, brain structures and connections may not form in the usual way, leading to cognitive impairment and developmental delay.

10. Effects on growth hormone and endocrine pathways
    Some reports describe links with endocrine problems and short stature. Abnormal transcription may affect hormones that control growth and weight, helping to cause short height and obesity.

11. De novo (new) mutations in the child
    In many cases, the AFF4 mutation happens for the first time in the child (de novo), and is not found in either parent. This new mutation in the egg or sperm is a direct cause of the disease in that child.

12. Autosomal dominant inheritance
    CHOPS syndrome follows an autosomal dominant pattern. This means one changed copy of the AFF4 gene is enough to cause the disease. A parent with CHOPS or with the mutation can pass it on to a child.

13. Possible parental germline mosaicism
    In rare genetic diseases like CHOPS, a parent can carry the mutation in some of their egg or sperm cells but not in their blood. This is called germline mosaicism and can explain repeated affected children in a family, even if parents seem healthy.

14. General DNA copying errors
    During cell division, DNA sometimes copies with small errors. Most errors are repaired, but some remain as mutations. Such general copying mistakes can be the background reason an AFF4 mutation appears.

15. Environmental factors that can trigger mutations (general)
    Strong radiation or certain chemicals can increase mutation risk in genes in general. While a direct link to CHOPS syndrome has not been proven, such factors are known ways any gene, including AFF4, might become mutated.

16. Abnormal protein stability
    Some AFF4 mutations make the protein harder to break down. The extra AFF4 then builds up in the cell and interferes with normal timing of transcription, causing wide-spread developmental problems.

17. Changes in gene networks for facial development
    The coarse facial appearance in CHOPS is likely due to disturbed networks of genes that shape the face. Mutant AFF4 changes the activity of these genes, leading to thick hair, bushy brows, and a round coarse face.

18. Disturbed skeletal gene signaling pathways
    Pathways that control cartilage, bone growth plates, and vertebral formation are affected by transcription changes. This disturbed signaling contributes to skeletal dysplasia and short bones.

19. Overlap with Cornelia de Lange–like pathways
    CHOPS shares some molecular mechanisms with Cornelia de Lange syndrome, especially in how transcription is regulated. This overlap suggests that changes in shared pathways can cause similar body patterns.

20. Very low frequency and chance events
    Because CHOPS is extremely rare, the cause in each case often reflects a chance mutation event in AFF4 rather than a common external trigger. This is why most families have only one affected person.

Symptoms

1. Cognitive impairment and intellectual disability
   Children with CHOPS syndrome usually have learning difficulties. They may sit, walk, talk, or solve problems later than other children. The level of disability can range from mild to severe.

2. Global developmental delay
   Many skills, such as motor skills, language, and social skills, are delayed. Children may need extra help with everyday activities and schooling.

3. Coarse facial features
   The face often looks round and coarse. There may be thick hair, bushy eyebrows (sometimes joined in the middle), wide-set eyes that may bulge slightly, a short up-turned nose, a long space between nose and upper lip, and down-turned corners of the mouth.

4. Short stature
   Most patients are shorter than other children of the same age and sex. Height is often below the 3rd percentile on growth charts. This shortness is linked to bone changes and sometimes hormone issues.

5. Obesity or overweight for height
   Many individuals become overweight or obese compared with their height. Extra body weight may develop in childhood or later, and can add stress on the heart, lungs, and joints.

6. Heart defects
   Common heart problems include septal defects (holes between heart chambers) and patent ductus arteriosus (a blood vessel that does not close after birth). These can cause tiredness, poor feeding, or breathing trouble.

7. Pulmonary (lung) problems
   Some children have weak airways, called laryngeal or tracheal malacia, and repeated lung infections. They may have chronic lung disease, noisy breathing, or need oxygen or breathing support.

8. Skeletal dysplasia and bone changes
   Bone problems include short fingers or toes (brachydactyly), abnormal vertebral bodies in the spine, and low bone mineral density. These changes can cause short height, a curved spine, or joint pain.

9. Eye and eyelid features
   The eyes may look wide apart and may seem to bulge (proptosis). Some patients have cataracts or mild optic nerve changes. These eye findings are part of the facial pattern of the syndrome.

10. Feeding problems and reflux
    Babies and children can have trouble feeding, slow weight gain at first, or later issues like reflux and delayed stomach emptying. They may spit up often, cough during feeds, or need special feeding plans.

11. Breathing and sleep issues
    Because of lung problems and airway weakness, some individuals have noisy breathing, sleep-disordered breathing, or need monitoring at night. Infections can make these symptoms worse.

12. Genitourinary anomalies
    Reported problems include cryptorchidism (undescended testes), kidney shape changes (such as horseshoe kidney), and reflux of urine from the bladder towards the kidneys. These can increase infection risk or affect fertility.

13. Microcephaly or small head size in some patients
    Some children have a head size that is smaller than average. This can relate to brain development problems and may be linked with more severe cognitive or motor delay.

14. Behavioral and emotional difficulties
    Because of developmental delay and medical stress, some individuals may have behavioral challenges, anxiety, or problems with attention. These need supportive care and sometimes specialist input.

15. Recurrent infections and general fatigue
    Chronic lung disease, heart strain, and feeding problems can lead to repeated infections and feeling tired. Children may not tolerate exercise as well as others and may need more rest.

Diagnostic tests

Physical exam–based tests

1. Full pediatric physical examination (Physical exam)
   The doctor checks the whole body, including height, weight, head size, face shape, chest, heart sounds, lungs, abdomen, and limbs. This helps spot the typical pattern of facial features, short stature, obesity, and skeletal changes seen in CHOPS.

2. Growth chart and body mass index (Physical exam)
   Measurements are plotted on growth charts to see if the child is short for age or overweight for height. This simple test shows the “short stature plus obesity” combination that is common in this syndrome.

3. Detailed dysmorphology exam (Physical exam)
   A specialist carefully studies facial features, hands, feet, and body shape. They look for coarse facial traits, short fingers, and spinal changes, and compare them with known CHOPS patterns.

4. Heart and lung clinical exam (Physical exam)
   The doctor listens with a stethoscope for heart murmurs, extra heart sounds, and abnormal breath sounds. This can suggest septal defects, ductus arteriosus problems, or chronic lung disease, which then need further tests.

5. Neurologic and developmental assessment (Physical exam)
   Simple tests of muscle tone, reflexes, walking, speech, and play skills help show the level of cognitive impairment and motor delay. This guides early therapy and helps track progress over time.

Manual and functional tests

6. Standardized developmental tests (Manual test)
   Tools such as structured play and question-and-answer tasks can measure language, motor skills, and problem solving. These manual tests give a clear picture of how far development is behind typical milestones.

7. Six-minute walk test or exercise tolerance test (Manual / functional)
   Walking or simple exercise tests can show how well the heart and lungs cope with activity. Shortness of breath or early tiredness may suggest heart or lung involvement.

8. Orthopedic joint and spine range-of-motion exam (Manual test)
   The clinician gently moves joints and checks the spine for stiffness, curvature, or pain. This simple hands-on test helps pick up skeletal dysplasia and related problems.

9. Feeding and swallowing assessment (Manual / functional)
   A therapist watches how the child sucks, chews, and swallows. They may try different textures of food to see if reflux, coughing, or choking occur, which is important for safe feeding plans.

10. Behavioral and psychological evaluation (Manual test)
    Structured interviews and play-based tests can assess behavior, mood, and social skills. This helps identify anxiety, attention problems, or other emotional needs that require support.

Laboratory and pathological tests

11. Targeted AFF4 gene sequencing (Lab / pathological)
    A blood test is used to read the DNA code of the AFF4 gene. Finding a disease-causing mutation confirms the diagnosis of CHOPS syndrome in a person with the typical clinical picture.

12. Broad genetic panels or exome sequencing (Lab / pathological)
    When the diagnosis is unclear, doctors may order a panel of genes or whole-exome sequencing. These tests look at many genes at once and can detect AFF4 mutations and rule out related conditions like Cornelia de Lange syndrome.

13. Chromosomal microarray (Lab / pathological)
    This test looks for extra or missing pieces of chromosomes. It may not always find AFF4 mutations, but it can detect other genetic causes of developmental delay if present, helping refine the diagnosis.

14. Routine blood tests and metabolic screens (Lab)
    Basic blood work (full blood count, liver and kidney tests) and sometimes metabolic screens are done to check general health, rule out other causes of delay, and assess safety before any treatments or surgeries.

15. Endocrine and growth hormone tests (Lab)
    Because short stature and obesity are common, doctors may check thyroid function, growth hormone levels, and other endocrine markers. Small hormone problems can worsen growth or weight issues and might be treatable.

Electrodiagnostic and physiologic tests

16. Electrocardiogram (ECG) (Electrodiagnostic)
    An ECG records the electrical activity of the heart. It can show heart rhythm problems or strain from structural defects. It is often used together with imaging of the heart.

17. Pulmonary function tests with spirometry (Electrodiagnostic / physiologic)
    Older children who can follow instructions may blow into a tube connected to a machine. This test measures lung volumes and flow to see how much the lung disease affects breathing.

18. Sleep study (polysomnography) (Electrodiagnostic)
    If there are signs of sleep-disordered breathing, a sleep study can monitor oxygen levels, breathing, and brain activity during the night. This helps detect apnea or other sleep-related breathing problems.

19. Electroencephalogram (EEG) when needed (Electrodiagnostic)
    If a child has unusual spells or suspected seizures, an EEG can measure brain electrical activity. While seizures are not a core feature of CHOPS, this test helps rule in or out extra brain problems.

Imaging tests

20. Heart and skeletal imaging (Imaging tests – grouped)
    Several imaging tests are useful in CHOPS syndrome. Echocardiography (heart ultrasound) shows heart structure and flow and can detect septal defects and ductus arteriosus. Chest X-rays show lung shape and repeated infections. Spine and limb X-rays reveal vertebral anomalies and bone changes. Brain MRI can show structural differences related to cognitive impairment. Together these imaging tests support the diagnosis and guide treatment.

Non-pharmacological (non-drug) treatments

1. Genetic counselling for family
   Genetic counselling helps parents understand why CHOPS syndrome happened, the role of the AFF4 gene, and the chance of the condition in future pregnancies. Counsellors also explain genetic testing for relatives and options such as prenatal or pre-implantation diagnosis, which can reduce anxiety and support informed family planning.

2. Early developmental intervention
   Starting early intervention programs in infancy can support motor skills, language, and social development. These programs break bigger skills into small steps and repeat them in a structured, playful way. For children with cognitive impairment, this approach can improve independence and quality of life over time.

3. Individualized education plan (IEP)
   Many children with CHOPS syndrome need special education support. An individualized education plan sets realistic learning goals, offers classroom aids, and adjusts teaching pace. Regular review of the plan helps teachers match school expectations to the child’s strengths and challenges.

4. Speech and language therapy
   Speech therapists work on understanding words, using language, and sometimes feeding and swallowing. They use simple pictures, gestures, and communication devices if needed. Early and regular speech therapy can help children express needs, reduce frustration, and improve social interaction.

5. Physiotherapy (physical therapy)
   Physiotherapists help with low muscle tone, delayed walking, joint stiffness, or skeletal deformities. They use stretching, strengthening, balance exercises, and posture training. Regular sessions can improve mobility, reduce pain, and support participation in daily activities and play.

6. Occupational therapy
   Occupational therapists train children in daily living skills such as dressing, feeding, and writing. They may recommend adaptive tools (special cutlery, pencil grips, seating supports) and environmental changes at home and school to make activities easier and safer.

7. Behavioural and psychological support
   Some children with complex syndromes experience anxiety, attention problems, or behavioural challenges. Psychologists and behavioural therapists use positive behaviour strategies, simple routines, and caregiver training to reduce stress and improve coping skills for both child and family.

8. Nutritional counselling and weight-management plans
   Because obesity is part of CHOPS syndrome, dietitians design balanced meal plans with controlled calories, adequate protein, and limited sugary drinks. They teach families about portion size, healthy snacks, and regular meal timing to prevent rapid weight gain and metabolic complications.

9. Structured physical activity program
   A gentle but regular physical activity plan, adjusted to heart and lung function, helps manage weight, strengthen muscles, and improve mood. Activities may include walking, supervised swimming, or low-impact games, with careful monitoring for breathlessness or fatigue.

10. Pulmonary rehabilitation and breathing exercises
    For children with lung involvement, respiratory therapists may teach breathing techniques, airway clearance methods, and energy-saving strategies. These exercises can improve lung function, reduce infections, and support better sleep and daily activity.

11. Sleep hygiene and positional therapy
    If sleep apnoea or nighttime breathing problems are present, improving sleep habits (fixed bedtime, avoiding screens before bed, proper pillow height) and using certain sleeping positions can support better breathing. In some cases, this is combined with devices like CPAP, which are medical but non-drug treatments.

12. Orthopaedic supports and bracing
    Children with skeletal dysplasia may benefit from braces, splints, or custom footwear to align joints and spine. These devices share weight more evenly, reduce pain, and make walking and standing safer, especially when bones are misshapen or fragile.

13. Regular cardiac monitoring
    Non-drug management of heart defects includes regular echocardiograms, ECGs, and specialist visits. Careful monitoring allows doctors to decide the best time for interventions and adjust activity levels to avoid over-strain on the heart.

14. Vaccination and infection-prevention strategies
    Following standard vaccination schedules and giving recommended additional vaccines for high-risk cardiac or pulmonary patients can lower the risk of serious infections. Hand hygiene, avoiding tobacco smoke, and early treatment of respiratory infections are also key non-drug strategies.

15. Family training and home-based therapy
    Teaching parents simple exercises, communication strategies, and positioning techniques allows them to continue therapy at home. This improves consistency, reinforces skills learned in clinic, and can reduce the number of hospital visits needed.

16. Social work and community support services
    Social workers help families access disability benefits, educational resources, and support groups. They also help coordinate appointments and services, which is important in rare syndromes that require many different specialists.

17. Psychosocial support groups
    Meeting other families living with CHOPS or similar rare conditions, in person or online, helps reduce feelings of isolation. Sharing practical tips and emotional experiences can improve coping and long-term mental health for caregivers and older children.

18. Assistive communication devices
    When spoken language is very limited, tablets or devices with symbol-based communication apps can allow children to express needs and participate in school and family life. Therapists choose devices suited to the child’s motor and cognitive abilities.

19. Home oxygen or non-invasive ventilation (if prescribed)
    Although equipment is medical, its day-to-day use is a non-drug strategy to support breathing. For some children with severe lung involvement, home oxygen or non-invasive ventilation at night can improve sleep quality, energy levels, and growth.

20. Regular comprehensive review in a rare-disease clinic
    Because knowledge about CHOPS is still growing, attending a specialised clinic or research centre when possible allows access to up-to-date advice, new studies, and coordinated care. This kind of follow-up is central to long-term management.

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Drug treatments

Important: Doses below are typical adult examples and may not be safe for children. In CHOPS syndrome, all medicines must be chosen and dosed only by specialist doctors.

1. Furosemide (Lasix) – loop diuretic
   Furosemide is a strong water tablet used to treat fluid overload (oedema) in heart failure. It makes the kidneys pass more salt and water, reducing swelling and breathlessness. FDA labels list it as indicated for oedema in adults and children with congestive heart failure and other conditions.

2. Hydrochlorothiazide – thiazide diuretic
   Hydrochlorothiazide is a milder water tablet sometimes added when extra fluid control is needed or blood pressure is high. It acts on different kidney tubules from furosemide. Combination tablets with lisinopril are approved for hypertension and require careful monitoring for low blood pressure and electrolyte changes.

3. Spironolactone – potassium-sparing diuretic
   Spironolactone blocks aldosterone, a hormone that causes salt and water retention and heart remodelling. It is used in chronic heart failure to improve symptoms and reduce hospitalisation but can raise blood potassium and cause hormonal side effects like breast tenderness.

4. Lisinopril (Zestril, Prinivil) – ACE inhibitor
   Lisinopril lowers blood pressure and reduces strain on the heart by blocking the renin-angiotensin-aldosterone system. FDA labels note benefits in hypertension and heart failure, but risks include cough, high potassium, kidney issues, and rare allergic swelling (angio-oedema).

5. Enalapril – ACE inhibitor
   Enalapril works similarly to lisinopril and is also used in heart failure and certain paediatric heart conditions. By widening blood vessels and reducing fluid retention, it can improve exercise tolerance, but it requires careful dose titration and blood tests.

6. Metoprolol succinate (Toprol-XL) – beta-blocker
   Metoprolol succinate is a long-acting beta-1 selective blocker used in chronic heart failure and hypertension. It slows the heart, lowers blood pressure, and improves survival in specific heart failure groups, but can worsen asthma and cause tiredness or low heart rate.

7. Carvedilol – beta-blocker with alpha action
   Carvedilol blocks both beta and alpha receptors, reducing heart rate and relaxing blood vessels. It is another key drug in heart failure therapy. Side effects can include dizziness, low blood pressure, and worsening of bronchospasm in susceptible patients.

8. Furosemide injection or subcutaneous formulations (e.g., Furoscix, Lasix ONYU)
   For severe fluid overload or when oral medicines are not possible, injectable or subcutaneous furosemide can be used. These formulations allow rapid or continuous removal of excess fluid in supervised settings but require close monitoring to avoid dehydration and kidney injury.

9. Fluticasone propionate inhalers (Flovent HFA/Diskus, others) – inhaled corticosteroid
   Fluticasone is an inhaled steroid for long-term asthma control. FDA labels describe it as maintenance therapy to reduce inflammation and prevent flare-ups, but not for sudden attacks. Side effects can include oral thrush and, at high doses, systemic steroid effects.

10. Short-acting beta-agonist inhalers (e.g., albuterol/salbutamol)
    These inhalers quickly relax airway muscles to relieve wheeze and shortness of breath. They are “rescue” medicines in lung disease but can cause tremor, rapid heart rate, and, in large doses, low blood potassium. In CHOPS, doses must respect heart status.

11. Long-acting bronchodilators (e.g., formoterol combined with inhaled steroids)
    In older patients with significant airway disease, long-acting bronchodilators in combination with inhaled steroids may be chosen for better day-night asthma or obstructive symptom control, under specialist guidance. They are not for very young children without clear indications.

12. ACE-inhibitor plus diuretic combinations (e.g., Zestoretic, Prinzide)
    Fixed-dose lisinopril-hydrochlorothiazide combinations may simplify treatment where both drugs are needed. FDA labels warn of excessive blood pressure reduction, kidney issues, and electrolyte problems, so frequent monitoring is essential, especially in complex syndromes.

13. Low-dose aspirin (when indicated by cardiology)
    In some patients with specific heart defects or after certain surgeries, low-dose aspirin is used to reduce blood clot risk. It works by blocking platelet aggregation but can increase bleeding and stomach irritation, so paediatric cardiologists decide carefully who should receive it.

14. Statins (e.g., atorvastatin) in older patients with obesity-related dyslipidaemia
    If a CHOPS patient reaches adolescence or adulthood with high cholesterol, statins may be used to lower cardiovascular risk. They reduce cholesterol synthesis in the liver but can cause muscle pain and rare liver enzyme elevation, requiring blood tests.

15. Metformin for obesity-related insulin resistance
    Metformin can help manage high blood sugar and insulin resistance in obese adolescents or adults. It reduces liver glucose production and improves insulin sensitivity but may cause stomach upset and, rarely, lactic acidosis, especially in kidney impairment.

16. Vitamin D and calcium (when deficient)
    Although supplements are not “drugs” in the classic sense, prescribed vitamin D and calcium can be essential if tests show deficiency, helping maintain bone strength in skeletal dysplasia and limited mobility. Over-supplementation risks kidney stones and abnormal blood calcium.

17. Growth hormone (GH) – only if a proven deficiency exists
    If proper testing shows true GH deficiency, specialist-supervised GH therapy may improve height outcomes. However, GH is not a routine treatment for CHOPS, and safety in complex syndromes must be carefully considered, especially with heart disease present.

18. Antibiotics for respiratory infections
    Antibiotics are used when bacterial infections such as pneumonia or recurrent ear infections occur. Quick treatment can prevent worsening lung damage, but antibiotics should be guided by cultures and local guidelines to avoid resistance.

19. Proton-pump inhibitors (PPIs) for severe reflux
    If gastro-oesophageal reflux contributes to breathing problems or poor weight gain, PPIs may be used to reduce stomach acid. Long-term use carries risks such as nutrient malabsorption and infection, so clinicians aim for the lowest effective dose and duration.

20. Sedation or anaesthesia drugs with special caution
    Children with CHOPS may sometimes need surgery or imaging under sedation. Anaesthetic drugs are not specific treatments for the syndrome, but they must be chosen carefully due to heart and lung problems. Anaesthesia teams plan tailored protocols and close monitoring.

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Dietary molecular supplements

Supplements are not proven cures for CHOPS syndrome. They should only be used if a doctor finds a deficiency or specific need.

1. Vitamin D
   Vitamin D supports bone mineralisation and immune function. In children with skeletal dysplasia, limited outdoor activity, or darker skin, deficiency is common. Supplement doses are based on blood levels to avoid toxicity, which can cause high calcium, nausea, and kidney problems.

2. Calcium
   Calcium is crucial for bone strength, muscle contraction, and heart rhythm. Supplementation may be recommended if dietary intake is low or if bone density is reduced, but excess calcium can lead to constipation and kidney stone risk, especially with dehydration or high vitamin D.

3. Omega-3 fatty acids (fish oil)
   Omega-3 fats can modestly improve triglyceride levels and may support heart health and inflammation balance. Typical preparations contain EPA and DHA. High doses can increase bleeding risk, particularly with aspirin or other blood thinners, so doses must be checked with a doctor.

4. Multivitamin tailored to age and needs
   A paediatric or adult multivitamin can help fill small nutrient gaps when appetite is limited or diet quality is poor. Formulas aligned to age reduce the chance of overdose of fat-soluble vitamins. They should not replace a balanced diet rich in fruits and vegetables.

5. Iron (if iron-deficiency anaemia is present)
   Iron supports red blood cell production and oxygen transport. Supplementation is only needed when tests confirm deficiency. Excess iron can cause gastrointestinal upset and, in large amounts, serious toxicity, so treatment is carefully dosed and monitored.

6. Vitamin B12 and folate
   These vitamins are needed for blood cell production and nervous system health. If laboratory tests show deficiency, targeted supplements may improve anaemia and support neurological function. Over-the-counter use without testing is discouraged because it can hide important diagnoses.

7. Coenzyme Q10 (CoQ10)
   CoQ10 plays a role in cellular energy production in mitochondria. Some clinicians use it off-label for patients with heart failure or fatigue, though evidence is modest. It is generally well tolerated but can interact with warfarin and other drugs, so medical review is needed.

8. L-carnitine
   Carnitine helps transport fatty acids into mitochondria for energy use. It may be used in certain metabolic or muscle disorders and could be considered if documented deficiency exists. Side effects include fishy body odour and gastrointestinal upset, and dosing must be individualized.

9. Probiotics
   Probiotic supplements or probiotic-rich foods may help with gut health, especially if frequent antibiotics disturb normal flora. Evidence for immune benefits is mixed, and probiotics can be risky in severely immunocompromised patients, so they should not be started without medical advice.

10. Protein-rich oral nutritional supplements
    For children with poor appetite or increased energy needs, specialised high-calorie, high-protein drinks may support growth and muscle mass. Dietitians choose formulas that match cardiac and renal status to avoid excess fluid or certain minerals.

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Immunity booster and regenerative / stem-cell-related approaches

There are no approved stem cell or gene therapies specifically for CHOPS syndrome today. The approaches below are general concepts, always experimental or supportive.

1. Optimised vaccination schedule
   Rather than “boosters” in pill form, proven immune protection comes from following national vaccination schedules and any extra vaccines recommended for heart or lung disease. Vaccines train the immune system to recognise germs and prevent severe infections, indirectly protecting vulnerable organs.

2. Adequate sleep, nutrition, and physical activity
   Good sleep, balanced diet, and regular gentle exercise support the immune system’s normal function. These basic “regenerative” habits reduce stress hormones and inflammation, helping the body recover after infections or surgery.

3. Haematopoietic stem cell transplantation (HSCT) – general concept
   HSCT is a procedure where bone-marrow stem cells are replaced to treat some blood and immune disorders. It is not standard for CHOPS but is mentioned as an example of regenerative treatment in genetic disease. It carries serious risks and is only used in specific, life-threatening conditions.

4. Emerging gene-based therapies in related conditions
   Gene therapy and gene-editing techniques are being studied in other monogenic disorders. They aim to correct the underlying DNA change in specific cells. For CHOPS, research is still at the very early stage, and no clinical gene therapy is available. Families may be informed about future trials by research centres.

5. Growth factor therapies in carefully selected cases
   In some skeletal dysplasias or growth disorders, growth hormone or other growth factors are considered when deficiencies are proven. In CHOPS, such drugs must be used very cautiously because they might stress the heart or worsen certain complications.

6. Participation in clinical trials at expert centres
   For rare diseases, clinical trials sometimes test new small molecules, biologics, or cell-based therapies that could have regenerative effects. Enrolling in such trials should be done only at recognised centres with full ethical review and detailed informed consent.

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Surgeries and procedures

1. Congenital heart defect repair
   Children with significant structural heart defects may need open-heart or catheter-based procedures to close holes, repair valves, or relieve outflow obstruction. The goal is to improve circulation, reduce heart failure symptoms, and prevent long-term damage to lungs and heart muscle.

2. Spinal or limb surgery for skeletal deformities
   Scoliosis, hip dislocation, or severe limb deformities due to skeletal dysplasia may require orthopaedic surgery. These operations aim to correct alignment, reduce pain, and improve mobility, often combined with bracing and physiotherapy.

3. Airway or lung-related procedures
   If airway malformations or severe obstructive sleep apnoea are present, procedures such as tonsillectomy, adenoidectomy, or airway surgery may be considered. These are done to improve airflow, reduce snoring and apnoea episodes, and protect the heart and brain from low oxygen.

4. Gastrostomy tube placement
   When feeding by mouth is unsafe or inadequate, a surgically placed feeding tube directly into the stomach (gastrostomy) can ensure reliable nutrition and medication delivery. This can ease caregiver stress and support steady growth while still allowing safe oral tastes if possible.

5. Orthopaedic tendon or soft-tissue releases
   In some children with joint contractures or abnormal muscle pull, soft-tissue surgeries are performed to lengthen tendons or relieve tight structures. This can improve range of motion, reduce pain, and make physiotherapy and bracing more effective.

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Prevention and long-term care strategies

1. Early diagnosis and genetic confirmation
   Confirming CHOPS syndrome with genetic testing as early as possible allows prompt screening of heart, lungs, and skeleton, which helps prevent avoidable complications through early intervention.

2. Routine heart and lung screening
   Regular cardiac and respiratory tests allow doctors to adjust medicines and plan surgery before severe heart failure or respiratory crises develop, reducing emergency admissions.

3. Vaccines and infection control
   Staying fully vaccinated and practicing good hygiene reduces the risk of pneumonia, flu, and other infections that can worsen lung and heart problems.

4. Healthy weight maintenance
   Preventing excessive weight gain through diet and activity lowers strain on heart and lungs, may improve sleep apnoea, and reduces risk of diabetes and high blood pressure later.

5. Avoiding tobacco smoke and pollutants
   Keeping the child away from cigarette smoke and heavy indoor or outdoor pollution helps protect lung function and reduces respiratory symptoms.

6. Regular dental and eye checks
   Many complex syndromes have dental and eye involvement. Routine checks help prevent tooth decay, treat vision problems early, and support overall quality of life.

7. Monitoring growth and puberty
   Tracking height, weight, and puberty timing helps endocrinologists decide whether additional tests or treatments are needed and pick up nutritional or hormonal issues early.

8. Emergency care plans
   Families can keep an emergency letter prepared by their specialist team, summarising diagnoses, heart and lung status, and usual medicines. This helps emergency doctors act quickly and safely if sudden illness occurs.

9. Transition planning to adult care
   As children with CHOPS syndrome grow older, planned transfer from paediatric to adult specialists prevents gaps in care and ensures that adult cardiology, respiratory, and rehabilitation services understand the condition.

10. Ongoing research participation and registry enrolment
    Joining rare-disease registries or research networks, where available, can improve knowledge about long-term outcomes and help future patients receive better evidence-based care.

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When to see doctors

Parents and caregivers should stay in regular contact with the child’s usual specialists, but some signs need urgent medical review. These include new or rapidly worsening shortness of breath, blue or very pale colour, chest pain, fainting, very rapid or very slow heartbeat, or sudden swelling of legs or abdomen, which may suggest heart failure or serious lung problems.

High fever, fast breathing, noisy breathing, or difficulty feeding can signal chest infection or airway compromise and should be assessed quickly, especially in children with known pulmonary involvement. Any seizure-like episode, sudden change in behaviour, marked drop in alertness, or suspected stroke symptoms also need emergency care.

Families should also contact their team if there is rapid weight gain, reduced urine output, unusual sleepiness, or new medication side effects such as severe cough, swelling of lips or face, rash, or unexplained vomiting and diarrhoea. Regular follow-ups are still needed even when the child seems stable, because complications can develop silently.

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What to eat and what to avoid

1. Focus on whole, minimally processed foods
   Meals built around vegetables, fruits, whole grains, lean protein, and healthy fats support growth without too many empty calories. This pattern helps manage obesity and supports heart health.

2. Choose lean protein sources
   Lean meats, fish, eggs, lentils, and dairy provide protein for muscle and bone without excessive saturated fat. Spreading protein intake across meals may help with energy and satiety.

3. Use healthy fats in moderation
   Small amounts of nuts, seeds, olive oil, and oily fish contribute beneficial fats. These should replace, not add to, saturated fats from fried foods, fatty meats, and commercial baked goods.

4. Keep salt intake modest
   Too much salt can worsen fluid retention and high blood pressure, especially when heart or kidney problems are present. Families can cook with herbs and spices instead of adding extra salt or using many salty convenience foods.

5. Limit sugary drinks and sweets
   Sugary drinks, juices, and desserts add calories without important nutrients and promote weight gain and dental decay. Water and unsweetened drinks should be the main fluids unless the medical team advises otherwise.

6. Watch portion sizes
   Using smaller plates, measuring snack portions, and avoiding eating straight from large packages can gently reduce energy intake without making the child feel deprived, which is important for sustainable weight control.

7. Regular meal and snack times
   Stable meal routines help control hunger and reduce overeating. Skipping meals can lead to bigger binges later, which is unhelpful in managing obesity linked to CHOPS syndrome.

8. Adequate fibre and fluids
   Fibre from fruits, vegetables, and whole grains, together with enough water, helps prevent constipation, which is common in children with limited mobility and multiple medicines.

9. Avoid fad diets or extreme restrictions
   Very low-calorie or one-food diets can harm growth and development and may interact badly with heart or lung disease. Any weight-management plan must be supervised by healthcare professionals familiar with CHOPS.

10. Coordinate diet with medicines
    Some medicines require timing with food or avoidance of certain foods (for example, grapefruit with some heart drugs). Dietitians and pharmacists can give specific advice so that diet and medication plans support each other.

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Frequently asked questions (FAQs)

1. Is CHOPS syndrome curable?
   At present, CHOPS syndrome is not curable, because it is caused by a change in the AFF4 gene, which is present in nearly all cells. Treatment focuses on managing symptoms, supporting development, and preventing complications so that the child can reach their best possible quality of life.

2. How rare is CHOPS syndrome?
   CHOPS syndrome is extremely rare, with only a small number of patients reported worldwide since it was first described in 2015. Because of its rarity, much of what we know comes from individual case reports and small series rather than large trials.

3. What causes CHOPS syndrome?
   The syndrome is caused by disease-causing variants in the AFF4 gene, which encodes a protein that is part of the super-elongation complex involved in gene transcription. These changes are usually autosomal dominant and often arise “de novo” (new in the child).

4. Can parents pass CHOPS syndrome to future children?
   If one parent carries an AFF4 variant, there is a 50% chance of passing it to each child. However, many cases are due to new variants not present in either parent. Genetic counselling and, when appropriate, parental genetic testing help clarify recurrence risk.

5. What are the main symptoms families notice first?
   Early signs often include unusual facial features, poor growth or short stature, feeding problems, developmental delay, and sometimes breathing or heart issues. As children grow, obesity, skeletal deformities, and learning difficulties become clearer.

6. How is CHOPS syndrome diagnosed?
   Diagnosis is usually made by combining clinical features with genetic testing, such as targeted gene panels or exome sequencing, that identify an AFF4 variant. This helps distinguish CHOPS from other syndromes with overlapping features.

7. What specialists should be involved in care?
   Most patients need a team including genetics, cardiology, pulmonology, orthopaedics, endocrinology, developmental paediatrics, dietetics, and rehabilitation therapies. Regular communication between team members improves safety and treatment planning.

8. Are there any specific CHOPS syndrome medicines?
   No medicines have been developed specifically for CHOPS. All current drug treatments are borrowed from standard care for heart failure, lung disease, obesity, and other complications. Research into targeted therapies is still at an early stage.

9. Can children with CHOPS go to mainstream school?
   Some children may attend mainstream school with support, while others may do better in special education settings. The decision depends on cognitive level, medical needs, and available support services. An individualized education plan is essential.

10. What is the life expectancy in CHOPS syndrome?
    Because so few individuals have been reported and follow-up is limited, long-term survival data are not clear. Early detection and active management of heart and lung disease are expected to improve outcomes, but individual prognosis varies widely.

11. Can lifestyle changes really help in a genetic syndrome?
    Yes. Although the gene change cannot be removed, lifestyle measures such as healthy diet, physical activity suited to the child’s capacity, infection prevention, and good sleep can significantly improve daily function and reduce complications.

12. Is pregnancy possible for someone with CHOPS syndrome?
    There are no large data sets, but in principle, adults with CHOPS may become parents. However, heart and lung status, mobility, obesity, and genetic transmission risks must be carefully assessed by cardiology, obstetrics, and genetics teams before pregnancy.

13. Should brothers and sisters be tested?
    Whether siblings need genetic testing depends on the specific family situation, including whether the AFF4 variant is de novo or inherited. Genetic counsellors help families decide about testing and explain benefits and limits.

14. Are there patient support organisations for CHOPS syndrome?
    Because CHOPS is so rare, there may not be syndrome-specific groups in every country, but rare disease organisations and some hospital-based networks bring families together, share information, and promote research connections.

15. Where can clinicians learn more?
    Clinicians can review resources from rare-disease databases such as GARD, Orphanet, MedlinePlus Genetics, and detailed reviews in the medical literature and disease-specific registries that discuss CHOPS syndrome’s clinical features and genetics.

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: February 03, 2025.