Brain Malformation–Congenital Heart Disease–Postaxial Polydactyly Syndrome

Brain malformation–congenital heart disease–postaxial polydactyly syndrome (also known as Goossens-Devriendt syndrome) is a very rare genetic condition. A baby is born with three main problems: (1) a brain malformation (the brain did not form in the usual way), (2) a congenital heart defect (the heart has a structural problem present at birth), and (3) postaxial polydactyly (an extra little finger or little toe side digit). Other features can include slow growth, special facial features, and sometimes hair and pituitary gland differences. Only a few families have been reported. Care focuses on early diagnosis, careful heart and brain care, and supportive therapies to help the child grow, learn, and stay healthy. rarediseases.info.nih.gov+2orpha.net+2

Brain malformation–congenital heart disease–postaxial polydactyly syndrome is a very rare genetic condition. Babies are born with several problems at the same time. The most typical trio is: (1) a brain malformation (for example, a small or under-formed cerebellum or an abnormal position/size of the pituitary gland), (2) a congenital heart defect, and (3) postaxial polydactyly, which means an extra little finger or little toe on the outer side of the hand or foot. Many children also have small size before birth (intrauterine growth restriction), hair changes (brittle or coarse hair, areas of balding at the temples), distinctive facial features, and may later show slow overall development and short stature. These features were first described together in two affected sisters and later summarized in rare-disease catalogs. rarediseases.info.nih.gov+1

Because so few people have been reported, doctors rely on those original case descriptions and curated databases to recognize the pattern. Different organ systems may be involved in different children, but the core pattern—brain changes, heart defect, and postaxial polydactyly—anchors the diagnosis. rarediseases.info.nih.gov

Other names

Experts and databases list several alternative names for the same condition. The most used synonym is Goossens–Devriendt syndrome (named after the team who reported the initial family). You may also see variations of the full descriptive name. rarediseases.info.nih.gov+1

• Goossens–Devriendt syndrome

• Brain malformation, congenital heart disease, postaxial polydactyly syndrome (punctuation/word order may vary across sites) rarediseases.info.nih.gov+1

Types

At present, there are no formally recognized subtypes (no “Type 1/Type 2”) in medical databases. Reports are very limited, and variation seems to reflect how strongly each organ system is affected rather than stable subcategories. Some children show pituitary and cerebellar findings; others show different brain features, but all cluster around the same triad. PubMed+1

Causes

Important context: Medical databases state the cause is genetic, but the exact gene has not yet been universally established for this specific named syndrome. Several clues come from the original family report and from related conditions that also combine polydactyly and heart/brain anomalies (often “ciliopathies,” disorders of tiny cell hairs called cilia). Items below reflect what is known and what is reasonably inferred from closely related biology; I state which is which. rarediseases.info.nih.gov+2PubMed+2

1. Pathogenic DNA change (general fact, known): A harmful change in DNA that disrupts normal development. This is the core cause category given in rare-disease catalogs. rarediseases.info.nih.gov

2. Hereditary (inherited) mutation (known as a possibility): The change may be passed from parents who do not have symptoms if the condition is recessive. In the first family, two sisters were affected, suggesting recessive inheritance is plausible. PubMed

3. De novo (new) mutation (known as a possibility): The change may arise for the first time in the child, not found in either parent. This is a general pattern for many rare genetic syndromes. rarediseases.info.nih.gov

4. Autosomal-recessive pattern (inferred): The sister-pair report supports a recessive model (two non-affected parents; more than one affected child). This is an inference from the pedigree, not a confirmed gene discovery. PubMed

5. Cilia-related pathway disruption (inferred from related disorders): Many syndromes with postaxial polydactyly and heart/brain anomalies are ciliopathies (e.g., Ellis–van Creveld, Bardet–Biedl). That suggests cilia biology might be involved here too. Frontiers+1

6. Sonic hedgehog (SHH) signaling disturbance (inferred): SHH helps pattern limbs and the brain; mis-signaling is linked to polydactyly and brain malformations in other conditions. anatomypubs.onlinelibrary.wiley.com

7. GLI3 pathway imbalance (inferred): GLI3 is a key limb-patterning transcription factor; GLI3-related disorders cause postaxial polydactyly. This suggests a plausible route to extra digits, though not proven for this named syndrome. ScienceDirect

8. Primary limb patterning gene defects (inferred): Genes that mark the front-to-back axis of the limb bud can cause polydactyly when altered. anatomypubs.onlinelibrary.wiley.com

9. Cardiac morphogenesis gene defects (inferred): Heart septation and outflow tract formation require dozens of genes. Overlap with limb/brain genes can produce the combined phenotype seen here. (General mechanistic inference.) obgyn.onlinelibrary.wiley.com

10. Pituitary/cerebellar development gene defects (inferred): Genes that guide pituitary placement and cerebellar vermis growth can, when altered, match the reported brain findings. (Inference consistent with the index cases.) PubMed

11. Consanguinity increasing recessive risk (general risk factor, not required): When parents are related, recessive conditions are more likely; not required here (the original parents were described as unrelated), but relevant across rare recessives. (General genetics principle.) rarediseases.info.nih.gov

12. Chromosomal micro-imbalances (inferred/ruled by test): Some multiple-anomaly syndromes come from small deletions/duplications; testing helps exclude this in individuals. (General mechanism in the differential.) rarediseases.info.nih.gov

13. Modifier genes (inferred): Background genetic differences may change how severe each feature is, explaining variability across patients in many rare syndromes. (General genetics principle.) rarediseases.info.nih.gov

14. Epigenetic dysregulation (inferred): Abnormal gene “on/off” switching can contribute to malformations in human syndromes; plausible but unproven here. (General mechanism.) rarediseases.info.nih.gov

15. Gene–environment interplay (general possibility): Databases note that environmental exposures can contribute to mutations or modify outcomes, but the primary driver is genetic. rarediseases.info.nih.gov

16. Noncoding regulatory mutations (inferred): Changes in enhancers that control limb/heart/brain genes can cause polydactyly and cardiac defects without altering the protein-coding sequence. (General mechanism from polydactyly biology.) anatomypubs.onlinelibrary.wiley.com

17. Copy-number neutral rearrangements (inferred): Balanced translocations can disrupt gene regulation; rare but described in similar phenotypes. (General mechanism.) rarediseases.info.nih.gov

18. Mosaic mutations (inferred): A mutation present in some cells can cause uneven features; this is a theoretical cause to consider during testing if results are negative. (General genetics.) rarediseases.info.nih.gov

19. Unknown gene yet to be identified (known reality): Because so few families are reported, the exact culpable gene(s) may still be undiscovered; exome/genome sequencing is recommended. rarediseases.info.nih.gov

20. Shared developmental network defects (inferred): A single change can ripple through connected networks that guide early organ formation, explaining brain–heart–limb co-involvement. (General developmental biology concept.) anatomypubs.onlinelibrary.wiley.com

Symptoms

1. Intrauterine growth restriction (IUGR): The baby grows slowly inside the womb and is small at birth. This is a frequent early clue that multiple body systems may be affected. rarediseases.info.nih.gov

2. Congenital heart defect (often atrial septal defect): A hole or structural problem in the heart present from birth. It may cause a heart murmur, fast breathing, or poor feeding. Careful heart imaging confirms it. rarediseases.info.nih.gov

3. Postaxial polydactyly (hands and/or feet): An extra little finger or toe on the outer side of the limb. This is a hallmark feature that helps doctors think about polydactyly-related syndromes. rarediseases.info.nih.gov+1

4. Cerebellar vermis hypoplasia / small cerebellum: The cerebellum (balance/coordination center) is underdeveloped, which can lead to delayed motor milestones and poor coordination. rarediseases.info.nih.gov

5. Abnormal posterior pituitary / neurohypophysis: The back part of the pituitary gland may be small or in an unusual place, which can contribute to hormone problems. PubMed

6. Hypotonia (low muscle tone): Babies feel “floppy” and may feed slowly or have delayed head control because of weaker tone. rarediseases.info.nih.gov

7. Severe global developmental delay: Milestones in movement, speech, and learning can be slow; therapy and early intervention are important. rarediseases.info.nih.gov

8. Short stature: Body height remains below the typical range for age. This may relate to overall growth disturbance and endocrine factors. rarediseases.info.nih.gov

9. Pulmonary artery stenosis: The artery from the heart to the lungs may be narrowed, causing a murmur or breathing symptoms. rarediseases.info.nih.gov

10. Renal hypoplasia: One or both kidneys are small. Screening is important because kidney function affects growth and blood pressure. rarediseases.info.nih.gov

11. Abnormal ears (dysplastic pinnae): The outer ears may look small, low-set, or oddly shaped. This helps clinical recognition during a dysmorphology exam. rarediseases.info.nih.gov

12. Depressed nasal bridge and anteverted nares: The middle of the nose looks low/flat and nostrils tilt upward, part of the distinctive facial pattern. rarediseases.info.nih.gov

13. Long, smooth philtrum and everted lower lip: The groove between nose and upper lip is long/smooth; the lower lip may turn outward. These are soft tissue signs that support the diagnosis. rarediseases.info.nih.gov

14. Hair anomalies (coarse, brittle hair; temporal balding): Hair texture is unusual and there may be thinning over the temples. This is uncommon and therefore diagnostically helpful. rarediseases.info.nih.gov

15. Upslanted palpebral fissures: The eyelid openings slant upward on the outer sides, a facial feature seen in this condition. rarediseases.info.nih.gov

Diagnostic tests

A) Physical examination

1. Newborn and infant dysmorphology exam: A specialist examines head shape, facial features, hands/feet, skin, hair, and body proportions to recognize the pattern that links the brain, heart, and extra digits. This first-line exam guides all later testing. rarediseases.info.nih.gov

2. Growth measurements over time: Regular tracking of weight, length/height, and head size shows small-for-age patterns and supports the history of prenatal growth restriction. rarediseases.info.nih.gov

3. Cardiac auscultation and vital signs: Listening for murmurs, checking oxygen level, breathing rate, and pulses can raise suspicion for heart defects or pulmonary artery narrowing that need imaging. rarediseases.info.nih.gov

4. Neurologic exam (tone, reflexes, coordination): Identifies hypotonia, delayed motor skills, or coordination issues that point to cerebellar involvement. rarediseases.info.nih.gov

5. Skin/hair examination: Notes coarse or brittle hair and temporal balding that match the published description. rarediseases.info.nih.gov

B) Manual / bedside developmental tests

6. Standard developmental screening (e.g., Bayley or similar tools): Simple, structured checks of movement, language, and problem-solving to grade delay and track progress over time. (General pediatric practice.) rarediseases.info.nih.gov

7. Feeding and suck–swallow assessment: Bedside checks by therapists identify low tone or coordination difficulties that affect feeding and growth. (General neonatal practice.) rarediseases.info.nih.gov

8. Gross/fine motor milestone assessments: Standardized checklists help document delays connected to cerebellar hypoplasia and low tone. (General pediatric neurology.) rarediseases.info.nih.gov

C) Laboratory and pathological tests

9. Chromosomal microarray (CMA): Screens for small missing or extra DNA segments that can cause multi-system birth differences; helpful to rule in/out alternative diagnoses. (General genetics protocol.) rarediseases.info.nih.gov

10. Clinical exome or genome sequencing: Looks for single-gene changes; recommended in rare multi-system syndromes. A negative result does not exclude the diagnosis, given that the exact gene for this named syndrome is not yet defined. rarediseases.info.nih.gov

11. Targeted ciliopathy gene panels (context-guided): Because many polydactyly-plus syndromes are ciliopathies, labs may run panels covering cilia/limb/heart development genes to seek an overlapping molecular diagnosis. (Inference from polydactyly genetics.) Frontiers

12. Pituitary hormone profile: If the posterior pituitary is small or displaced, labs for cortisol/ACTH, thyroid, growth hormone/IGF-1, and water–salt balance (ADH) help detect treatable endocrine problems. (Based on reported pituitary anomalies.) PubMed

13. Renal function testing (creatinine, electrolytes, urinalysis): Screens for kidney impact when renal hypoplasia is present. (General nephrology practice.) rarediseases.info.nih.gov

14. Metabolic screening (as indicated): Broad newborn screens and targeted tests help exclude metabolic conditions that can mimic developmental delay. (General pediatric genetics.) rarediseases.info.nih.gov

D) Electrodiagnostic / physiologic tests

15. Electrocardiogram (ECG): Checks heart rhythm and conduction; useful with structural heart disease or surgery planning. (General cardiology.) rarediseases.info.nih.gov

16. Pulse oximetry (oxygen saturation monitoring): Non-invasive check to detect low oxygen due to heart defects or pulmonary artery stenosis. (Neonatal standard.) rarediseases.info.nih.gov

17. Electroencephalogram (EEG) if indicated: If seizures or abnormal tone patterns are suspected, EEG can look for epileptiform activity related to brain malformation. (General neurology.) rarediseases.info.nih.gov

E) Imaging tests

18. Echocardiography (fetal or postnatal): Ultrasound of the heart confirms septal defects or vessel narrowing and guides treatment. (Key test in the reported family.) PubMed

19. Brain MRI: Best view of the cerebellum and vermis, cortex, and pituitary region; shows hypoplastic vermis or an ectopic/posterior pituitary. (Anchors the “brain malformation” part of the triad.) PubMed

20. Dedicated pituitary MRI protocol: Focused sequences of the sellar region assess posterior pituitary size/position and the pituitary stalk. (Based on index case findings.) PubMed

21. Renal ultrasound: Screens for small kidneys or other urinary tract differences with no radiation. (Matches reported renal hypoplasia.) rarediseases.info.nih.gov

22. Skeletal radiographs of hands/feet: Document the type of polydactyly (Type A/B) and guide surgical discussions if needed. (General polydactyly care.) ncbi.nlm.nih.gov

23. Cranial ultrasound in neonates (if MRI not immediately available): A bedside screen for major brain differences in the first days of life. (General neonatal practice.) rarediseases.info.nih.gov

---

Non-pharmacological treatments

1) Coordinated care plan (multidisciplinary clinic)
Description: A single care plan brings together pediatric cardiology, neurology, genetics, orthopedics/hand surgery, endocrinology (for pituitary issues), physical/occupational therapy, speech therapy, nutrition, and social work. Families get a calendar of visits, a written action plan for emergencies (breathing trouble, seizures, poor feeding), and goals for development and school. The plan includes how to monitor weight gain, sleep, feeding, and medicines; when to repeat heart/brain imaging; and how to connect with early-intervention services.
Purpose: Reduce medical risk, avoid duplicated tests, and support the family.
Mechanism: Team care improves information flow and timely decisions; it prevents gaps and harmful delays.

2) Genetic counseling and family planning
Description: A certified genetic counselor explains what is known about the syndrome, inheritance patterns, testing options for parents/siblings, and choices for future pregnancies (prenatal ultrasound/MRI, chorionic villus sampling, or amniocentesis if a causal variant is known). Counselors also screen for related ciliopathy syndromes that can look similar.
Purpose: Informed choices and early detection.
Mechanism: Risk calculation and targeted testing based on Mendelian inheritance and known gene pathways. rarediseases.info.nih.gov+1

3) Early-intervention developmental therapy (0–3 years)
Description: Weekly home- or clinic-based sessions to boost motor skills, language, social skills, and feeding. Therapists teach parents positioning, play activities, and communication strategies.
Purpose: Maximize brain plasticity during the first years of life.
Mechanism: Repetition and task-specific training strengthen neural connections that support movement and language.

4) Physical therapy (PT)
Description: PT improves head control, rolling, sitting, crawling, and walking. It uses gentle stretches, balance training, and play-based exercises.
Purpose: Prevent contractures and build strength/endurance.
Mechanism: Progressive loading improves muscle strength and motor patterns.

5) Occupational therapy (OT)
Description: OT focuses on fine motor skills (grasp/release), hand use after polydactyly surgery, self-care (feeding, dressing), and adaptive tools.
Purpose: Improve daily independence.
Mechanism: Task-oriented practice rewires motor planning and hand-eye coordination.

6) Speech-language therapy (SLT)
Description: SLT supports early communication, feeding coordination, and later speech/language. If needed, augmentative and alternative communication (AAC) is added.
Purpose: Reduce frustration and promote language.
Mechanism: Structured language input and oral-motor training reinforce neural pathways for communication.

7) Feeding and nutrition program
Description: A pediatric dietitian designs high-calorie, heart- and brain-friendly plans, monitors growth curves, and addresses reflux or aspiration risk. Thickened feeds, special nipples, or tube feeding may be used if needed.
Purpose: Safe feeding and steady growth.
Mechanism: Adjusting calorie density and feeding techniques matches the child’s energy needs and swallowing skills.

8) Cardiac monitoring & home pulse oximetry (when recommended)
Description: Families learn to check oxygen levels, heart rate, and signs of heart failure (sweating with feeds, fast breathing, poor weight gain).
Purpose: Early detection of heart strain.
Mechanism: Trend tracking triggers timely clinic calls and medication/surgery adjustments.

9) Seizure safety education
Description: Caregivers learn seizure first aid, when to call emergency services, and how to record events.
Purpose: Reduce injury and speed treatment.
Mechanism: Prepared responses shorten time to care.

10) Vision and hearing screening
Description: Regular audiology and ophthalmology checks find treatable problems that affect learning and language.
Purpose: Protect sensory inputs for development.
Mechanism: Early correction (glasses, hearing support) improves brain learning.

11) Orthopedic/hand surgery evaluation
Description: A pediatric hand surgeon reviews the extra finger/toe and plans surgery for function and appearance, usually in infancy/toddler years.
Purpose: Improve hand/foot function and reduce shoe/skin issues.
Mechanism: Surgical removal and tendon/ligament balancing optimize biomechanics.

12) Pediatric cardiothoracic surgery consult
Description: The heart defect (e.g., septal defects, AV canal) is mapped and repair timing planned. Parents learn benefits/risks, need for bypass, and hospital course.
Purpose: Correct the structural defect to improve circulation and growth.
Mechanism: Surgical reconstruction restores normal blood flow pathways. rarediseases.info.nih.gov

13) Neuroimaging-guided follow-up (MRI/ultrasound)
Description: Imaging defines the brain malformation and guides therapy (e.g., hydrocephalus monitoring, pituitary evaluation).
Purpose: Targeted surveillance and intervention.
Mechanism: Imaging reveals structural issues that respond to shunting, hormones, or therapy.

14) Endocrine assessment & hormone replacement (if pituitary issues)
Description: Testing for growth hormone, thyroid, adrenal, and puberty hormones, with replacement if low.
Purpose: Support growth, energy, and development.
Mechanism: Restoring physiologic hormone levels normalizes metabolism and growth.

15) Vaccination schedule plus RSV prevention plan
Description: Keep all routine vaccines on time. Infants with significant heart disease may be candidates for seasonal RSV prevention (see Drug #20, palivizumab).
Purpose: Prevent avoidable infections and hospitalizations.
Mechanism: Active immunization builds adaptive immunity; passive immunization provides seasonal antibody protection. FDA Access Data

16) Respiratory therapy and airway clearance (as needed)
Description: Techniques include positioning, gentle chest physiotherapy, and suction training if secretions are thick.
Purpose: Improve breathing comfort and oxygenation.
Mechanism: Better mucus movement reduces atelectasis/infection risk.

17) Sleep safety & positioning
Description: Guidance on safe sleep, head shaping, reflux positioning, and equipment (elevated head crib wedges only if clinician-approved).
Purpose: Reduce aspiration and improve rest.
Mechanism: Gravity-assisted positioning and routine improve airway protection.

18) Parent training & psychosocial support
Description: Counseling, respite resources, peer groups, and mental health support reduce caregiver stress and improve adherence.
Purpose: Sustain long-term family resilience.
Mechanism: Coping skills and social support buffer stress.

19) School-age individualized education plan (IEP)
Description: Education specialists plan classroom supports, therapy minutes, and accommodations (seizure/action plans, rest breaks).
Purpose: Promote learning and inclusion.
Mechanism: Legal/educational frameworks secure services.

20) Transition-to-adulthood roadmap
Description: From age ~12 onward, build self-management skills, transfer medical summaries, and identify adult cardiology/neurology clinics.
Purpose: Safe handoff to adult care.
Mechanism: Planned transfer avoids care gaps.

---

Drug treatments

Important: There is no single “cure” drug for this ultra-rare syndrome. Medicines target specific problems—heart failure symptoms, duct-dependent lesions in newborns, seizures, or infections. Dosing must be individualized by the child’s clinicians.

1) Furosemide (Lasix®) – loop diuretic
Class: Diuretic. Typical pediatric dose: Oral 1–2 mg/kg/dose; IV 1 mg/kg slow push; doses titrated by cardiology. Timing: 1–4 times/day based on response. Purpose: Relieve fluid overload and heart failure symptoms (sweating with feeds, swelling, fast breathing). Mechanism: Blocks Na-K-2Cl transporter in the loop of Henle to increase urine and reduce lung/venous congestion. Side effects: Dehydration, low potassium/sodium, ototoxicity with rapid IV dosing. FDA labeling supports pediatric dosing and cautions. FDA Access Data+1

2) Spironolactone – potassium-sparing diuretic
Class: Aldosterone antagonist. Dose: ~1–3 mg/kg/day divided; titrate. Timing: Daily or BID. Purpose: Add-on diuretic to reduce potassium loss from loop diuretics. Mechanism: Blocks aldosterone in distal nephron; limits sodium/water reabsorption. Side effects: High potassium, GI upset, rarely endocrine effects. (Pediatric use is common off-label under cardiology guidance; always follow your cardiologist’s plan.)

3) Chlorothiazide/Hydrochlorothiazide – thiazide diuretics
Class: Distal tubule diuretics. Dose: per weight; used with or instead of loop diuretics. Purpose/Mechanism: Extra diuresis by blocking sodium reabsorption in the distal tubule. Side effects: Low sodium/potassium, dehydration. (Used under pediatric cardiology guidance.)

4) Captopril (Capoten®) – ACE inhibitor
Class: ACE inhibitor. Dose: Small test dose, then titrate (e.g., 0.05–0.1 mg/kg/dose up to mg/kg ranges set by cardiology). Timing: TID. Purpose: Afterload reduction in heart failure; improves forward flow. Mechanism: Blocks angiotensin-II formation; decreases systemic vascular resistance; may improve remodeling. Side effects: Hypotension, kidney effects, cough, high potassium. FDA label describes heart-failure use and titration. FDA Access Data

5) Enalapril – ACE inhibitor
Class/Dose: Weight-based; BID. Purpose/Mechanism: Similar to captopril with longer action; used in pediatric heart failure by specialists. Side effects: Like other ACE inhibitors (BP, renal monitoring).

6) Valsartan – angiotensin receptor blocker (ARB)
Class: ARB. Dose: Age-/weight-adjusted; uptitrate as tolerated. Purpose: Alternative when ACE inhibitors not tolerated. Mechanism: Blocks angiotensin-II receptor. Side effects: Hypotension, high potassium, renal effects. FDA labeling covers heart-failure dosing in older children/adults; pediatric decisions are specialist-guided. FDA Access Data

7) Alprostadil (Prostaglandin E1) – ductus arteriosus maintainer (neonates)
Class: Prostaglandin analog. Dose: Continuous IV infusion (weight-based) in the NICU. Timing: Temporarily in the first days/weeks of life. Purpose: Keep the ductus arteriosus open in newborns with ductal-dependent heart defects to maintain life-saving blood flow until surgery/catheter therapy. Mechanism: Relaxation of ductal smooth muscle keeps ductus patent; stabilizes oxygen delivery. Side effects: Apnea (requires ventilatory support), hypotension, fever, gastric outlet obstruction with prolonged use. FDA and review documents describe neonatal use for ductal-dependent CHD. FDA Access Data+2FDA Access Data+2

8) Dopamine – inotrope/vasopressor (ICU)
Class: Catecholamine. Dose: Weight-based IV infusion with continuous monitoring. Purpose: Support heart function and blood pressure during acute decompensation or peri-operative periods. Mechanism: Dose-dependent β- and α-adrenergic effects improve contractility and vascular tone. Side effects: Arrhythmias, tissue injury with extravasation. FDA labeling provides dosing/precautions. FDA Access Data+1

9) Dobutamine – inotrope (ICU)
Class: β1-agonist. Dose: Weight-based IV infusion. Purpose/Mechanism: Increases contractility and cardiac output with less effect on vascular tone than dopamine. Side effects: Tachycardia, arrhythmias. (ICU specialist drug.)

10) Milrinone – inodilator (ICU/post-op CHD)
Class: PDE-3 inhibitor. Dose: IV infusion. Purpose: Improves contractility and decreases afterload; often used after cardiac surgery. Mechanism: Increases cAMP in cardiac/vascular muscle. Side effects: Hypotension, arrhythmia. (Specialist use.)

11) Levetiracetam (Keppra®) – anti-seizure
Class: Antiepileptic. Dose: Weight-based; oral/IV; start low and titrate. Purpose: Treat seizures related to brain malformation. Mechanism: Modulates synaptic vesicle protein SV2A to reduce neuronal excitability. Side effects: Sleepiness, mood changes. FDA labels include pediatric indications from 1 month of age (formulation specific). FDA Access Data+1

12) Midazolam or Diazepam – rescue seizure medicine
Class: Benzodiazepines. Dose: Buccal, intranasal, rectal, or IV per protocol. Purpose: Stop prolonged seizures. Mechanism: Enhances GABA-A inhibition. Side effects: Drowsiness, breathing suppression (medical supervision).

13) Propranolol/Metoprolol – beta-blockers
Class: β-adrenergic blockers. Dose: Weight-based. Purpose: Manage certain arrhythmias or control heart rate as advised by cardiology. Mechanism: Slow AV-node conduction, reduce myocardial oxygen demand. Side effects: Bradycardia, low BP.

14) Digoxin – cardiac glycoside
Class: Positive inotrope. Dose: Carefully weight-based with serum level monitoring. Purpose: Selected infants/children with heart-failure physiology; specialist-decided. Mechanism: Inhibits Na⁺/K⁺-ATPase → ↑intracellular Ca²⁺; increases contractility. Side effects: Narrow therapeutic window, arrhythmias.

15) ACE-inhibitor alternatives (lisinopril)
Class: ACE inhibitor. Dose/Mechanism: Similar to captopril; once-daily dosing in older children. Use: When appropriate per cardiology.

16) Diuretic adjuncts (metolazone)
Class: Thiazide-like diuretic. Purpose: Add-on in refractory fluid overload. Mechanism/Side effects: Potent distal sodium blockade; careful electrolyte monitoring.

17) Antibiotics for bacterial infections/endocarditis risks
Class: Penicillins/cephalosporins as indicated for infections; not routine long-term prophylaxis unless cardiology/dentistry advise around procedures. Purpose: Treat infections promptly to protect heart/lungs. Mechanism: Pathogen-specific killing. (Follow local guidelines.)

18) Iron, folate, and vitamin support when deficient
Class: Nutrient repletion. Purpose: Treat anemia/nutrient deficits that worsen cardiac work or development. Mechanism: Restores normal hematologic and metabolic function.

19) Proton-pump inhibitor or H2 blocker (if severe reflux affects feeding/growth)
Class: Acid suppression. Purpose: Reduce pain/aspiration risk. Mechanism: Lowers gastric acid; improves comfort and intake. Note: Use shortest effective duration.

20) Palivizumab (Synagis®) – seasonal passive immunization for RSV in high-risk infants
Class: Monoclonal antibody against RSV F protein. Dose: 15 mg/kg IM monthly during RSV season (max five doses), as per eligibility (e.g., hemodynamically significant CHD). Purpose: Reduce RSV hospitalizations in high-risk infants. Mechanism: Neutralizes RSV to prevent severe lower-respiratory disease. Side effects: Injection-site reactions, fever; rare hypersensitivity. FDA labeling and pediatric trials include infants with significant CHD. (Note: Some markets report supply and product changes; clinicians will advise current practice.) FDA Access Data+1

---

Dietary molecular supplements

Always discuss any supplement with your child’s care team to check for drug interactions or kidney issues.

1) Omega-3 fatty acids (DHA/EPA)
Description (≈150 words): Helpful for heart health and brain cell membranes. In infants/children, sources include breastmilk, fortified formula, or diet as age allows (oily fish, algae oils). Dose: Pediatric dosing varies; follow clinician guidance. Function/Mechanism: Incorporates into neuronal and cardiac cell membranes; may support anti-inflammatory signaling.

2) Coenzyme Q10
Description: Mitochondrial cofactor that supports cellular energy (ATP). Dose: Weight-based (often 2–5 mg/kg/day in divided doses; clinician-guided). Function: May help energy metabolism in heart muscle. Mechanism: Electron transport chain support and antioxidant effects.

3) L-carnitine
Description: Transports fatty acids into mitochondria for energy. Dose: Weight-based; often 50–100 mg/kg/day divided. Function: Supports cardiac/neuromuscular energy use. Mechanism: Carnitine shuttle for β-oxidation.

4) Vitamin D
Description: Bone and immune support; many children are low. Dose: Per pediatric guidelines (e.g., 400–1000 IU/day depending on age and level). Function: Calcium homeostasis; muscle function. Mechanism: Nuclear receptor–mediated gene regulation.

5) Magnesium
Description: Supports nerve/muscle function and rhythm stability. Dose: Weight-based; avoid excess with kidney issues. Function: Co-factor in hundreds of enzymes. Mechanism: Modulates ion channels and NMDA receptors.

6) B-complex (B1, B2, B6, B12) and Folate
Description: Support energy metabolism and red blood cell production; folate is critical pre-pregnancy. Dose: Age-appropriate RDA or deficiency-directed. Function: Cofactors for carbohydrate/amino-acid metabolism. Mechanism: Enzymatic coenzymes for mitochondrial pathways.

7) Iron (only if deficient)
Description: Treat iron-deficiency anemia that can worsen heart workload. Dose: 3–6 mg/kg/day elemental iron (medical supervision). Function: Hemoglobin synthesis to carry oxygen. Mechanism: Restores iron stores and erythropoiesis.

8) Zinc
Description: Supports growth and immune function. Dose: RDA-based; avoid overdosing. Function: Enzymatic and transcription factor co-factor. Mechanism: DNA/RNA synthesis and immune cell signaling.

9) Probiotics (selected strains)
Description: May help antibiotic-associated diarrhea and gut comfort. Dose: Strain-specific CFUs per label; discuss with clinician. Function: Microbiome balance. Mechanism: Competitive exclusion and metabolite signaling.

10) MCT (medium-chain triglyceride) oil (dietitian-guided)
Description: Easier-to-absorb calories for infants/children with growth issues. Dose: Titrated into feeds. Function: Energy dense nutrition. Mechanism: Direct portal absorption and rapid oxidation.

---

Drugs for “immunity/regenerative/stem-cell

There are no FDA-approved “regenerative” or stem-cell drugs to treat this specific syndrome. The safe, evidence-based focus is prevention and support.

1) Palivizumab (Synagis®) – Passive immunity against RSV in eligible infants with significant CHD; reduces RSV hospitalization risk. Dose: 15 mg/kg IM monthly in season. Mechanism: Neutralizing monoclonal antibody. FDA Access Data

2) Routine vaccines (per national schedule) – Strong “immune-boosting” by teaching the immune system to fight infections like pneumococcus, influenza, pertussis. Mechanism: Active immunization builds specific memory.

3) Influenza vaccine (annual, age-appropriate) – Protects lungs/heart during flu season; important in CHD. Mechanism: Antibody and T-cell responses to flu antigens.

4) Vitamin D (if low) – Supports balanced immune responses; correct deficiency to lower infection risk. Mechanism: Nuclear receptor signaling in immune cells.

5) Zinc (if low) – Restores normal innate/adaptive immunity. Mechanism: Cofactor for lymphocyte function.

6) IVIG (intravenous immunoglobulin) – selected cases only – Considered if a documented antibody deficiency is found by immunology; not routine. Mechanism: Provides pooled antibodies for temporary protection.

---

Surgeries

1) Cardiac defect repair (e.g., VSD/ASD/AV canal repair)
Procedure: Open-heart surgery with cardiopulmonary bypass to close septal holes or reconstruct valves/septa. Why: To normalize blood flow, reduce lung pressure/heart failure, and support growth. rarediseases.info.nih.gov

2) Temporary ductal support to definitive repair (neonates)
Procedure: Stabilize with alprostadil and, when indicated, catheter/surgical palliation before full repair. Why: Maintain life-saving circulation until anatomy allows a durable fix. FDA Access Data

3) Excision of postaxial polydactyly (hand/foot surgery)
Procedure: Remove extra digit; balance tendons/ligaments; protect nerves. Why: Improve function, shoe fit, and appearance.

4) CSF shunt or endoscopic third ventriculostomy (selected brain malformations with hydrocephalus)
Procedure: Divert cerebrospinal fluid to relieve pressure. Why: Protects brain tissue and vision.

5) ENT/airway procedures (as needed)
Procedure: Address airway anomalies (e.g., laryngomalacia) or feeding tubes when severe aspiration occurs. Why: Ensure safe breathing and nutrition.

---

Preventions

1. Preconception folate (400–800 mcg/day for most, or as advised) to lower neural tube defects.

2. Avoid teratogens (alcohol, tobacco, illicit drugs; review prescription meds in pregnancy).

3. Optimize maternal health (control diabetes, thyroid disease; take prenatal vitamins).

4. Genetic counseling if there is family history or a known variant. rarediseases.info.nih.gov

5. Prenatal screening (ultrasound, fetal echo; fetal MRI when advised) for early planning.

6. Deliver in a center with NICU and pediatric cardiology/cardiac surgery when known CHD is present.

7. Newborn critical CHD pulse-ox screening before discharge.

8. Complete vaccinations on schedule; consider RSV prophylaxis if eligible. FDA Access Data

9. Hand hygiene and infection avoidance during seasons of high respiratory viruses.

10. Regular growth and development follow-up to catch issues early.

---

When to see a doctor

• Newborn feeding problems: sweating, fast breathing, tiring after a few minutes, poor weight gain.

• Blue or very pale color, fast or difficult breathing, or low oxygen readings.

• Long or clustered seizures, or any first seizure.

• Bulging soft spot (fontanelle), repeated vomiting, very irritable or very sleepy baby.

• Fever in an infant <3 months, or any high fever with breathing problems.

• Signs of dehydration: very few wet diapers, very dry mouth, sunken eyes.

• Worsening swelling of legs/eyes/abdomen.

• Any sudden change that worries you—trust your instincts and call your clinician or emergency services.

---

What to eat and what to avoid

What to eat:

1. Balanced, energy-dense meals planned by a pediatric dietitian to support growth.

2. Healthy fats (avocado, olive oil; MCT if prescribed) for safe extra calories.

3. Protein at each meal (eggs, tofu, fish/chicken as age-appropriate) to build muscle.

4. Fruits and vegetables for vitamins, minerals, and fiber.

5. Omega-3 sources (oily fish or algae oils) to support heart/brain health.

What to avoid:

1. Very salty foods (chips, instant noodles, processed meats) if heart failure is present.

2. Sugary drinks that displace nutritious calories.

3. Unpasteurized foods that raise infection risk.

4. Herbal supplements without clinician review (possible interactions).

5. Excess fluid if your cardiologist recommends a fluid limit.

---

Frequently asked questions

1) Is there a cure?
There is no single cure. Treatment focuses on the heart defect, brain-related needs, and extra digits. Early, team-based care helps children do their best. rarediseases.info.nih.gov

2) What causes it?
It is genetic. Only a few families are reported, and researchers think it relates to genes that guide early body patterning. Testing may or may not find the exact change. PubMed

3) Is it the same as McKusick-Kaufman or Ellis-van Creveld?
No, but they can look similar (all can have postaxial polydactyly and heart defects). Your genetics team compares features and tests to tell them apart. ncbi.nlm.nih.gov+1

4) How is it diagnosed?
Doctors use the birth features (brain imaging, heart echo, extra digits), exam, and sometimes gene testing. Orphanet and GARD list it as an ultra-rare syndrome. orpha.net+1

5) Will my child need heart surgery?
Many do, depending on the exact defect. Timing is decided by pediatric cardiology and heart surgeons. rarediseases.info.nih.gov

6) Can brain differences cause seizures or hormone issues?
They can. Neurology treats seizures (often with levetiracetam), and endocrinology checks pituitary-related hormones. FDA Access Data

7) Why is RSV prevention important?
CHD increases risk from RSV. Eligible infants may receive monthly palivizumab during the RSV season to cut hospitalization risk. FDA Access Data

8) Will my child’s extra finger/toe always be removed?
Usually yes if it affects function, shoe wear, or skin problems. A hand/orthopedic surgeon advises the best timing.

9) Can diet help the heart?
A dietitian can make calorie-dense, lower-salt plans to support growth while easing heart workload.

10) What about school and learning?
Early therapy and an Individualized Education Plan help with learning and communication.

11) Is this inherited?
It may be. A genetic counselor estimates risks for future pregnancies and explains testing options. rarediseases.info.nih.gov

12) How often are checkups?
Frequently in infancy (cardiology, neurology, growth), then as advised. Keep vaccines on schedule.

13) Can we exercise?
Gentle, developmentally appropriate activity is healthy; your cardiologist will set limits based on the heart defect and oxygen levels.

14) Are stem-cell treatments available?
No approved stem-cell therapies treat this syndrome. Be cautious with clinics offering unproven treatments.

15) What is the long-term outlook?
Outcomes vary widely with the exact heart and brain findings and with access to specialized care. Early, comprehensive support improves quality of life. PubMed

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: November 02, 2025.

PDF Documents For This Disease Condition References