Alveolar Capillary Dysplasia with Misalignment of Pulmonary Vessels

Alveolar capillary dysplasia with misalignment of pulmonary vessels (often shortened to ACD/MPV) is a rare birth condition that affects how a baby’s lungs develop. In healthy lungs, tiny air sacs (alveoli) sit next to tiny blood vessels (capillaries). Oxygen moves from air to blood across a very thin wall. In ACD/MPV, that normal “air–blood” contact is poorly built. There are too few working capillaries near the air sacs, the walls are thick, and small lung arteries are unusually muscular. Some small veins also run in the wrong place (they sit alongside airways and arteries instead of in their usual path). Because of this faulty layout, oxygen cannot get into the blood well, and blood pressure in the lungs becomes very high soon after birth. Babies develop severe low oxygen that does not improve with usual treatment. ACD/MPV is usually caused by harmful changes in or near a gene called FOXF1, which guides lung blood-vessel development before birth. The condition is typically lethal without lung transplantation. Genetic Rare Disease Center+3PMC+3MedlinePlus+3

ACD/MPV is a very rare condition that affects a newborn baby’s lungs. In ACD/MPV, the tiny air sacs (alveoli) and their blood vessels (capillaries) do not form in the normal way before birth. Because of this, oxygen cannot easily move from air into blood. Babies get severe breathing trouble and low oxygen soon after birth. A special feature under the microscope is that some pulmonary veins run in the wrong place, next to the arteries, instead of in the usual paths—this is called “misalignment of the pulmonary veins.” The small pulmonary arteries are often thickened, which raises lung blood pressure (persistent pulmonary hypertension of the newborn, PPHN). ACD/MPV is usually caused by changes (variants or deletions) in a gene called FOXF1 or its distant enhancer region on chromosome 16q24.1. PubMed+3PMC+3MedlinePlus+3

Other names

• Alveolar capillary dysplasia (ACD)

• ACD with misalignment of pulmonary veins (ACDMPV)

• Congenital alveolar capillary dysplasia

• Pulmonary vein misalignment syndrome (historic/partial term)
  These names all point to the same core problem: an abnormal “wiring diagram” of the lung’s tiniest vessels present from birth. National Organization for Rare Disorders+1

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Types

Doctors now recognize several patterns. Describing them helps families and teams understand why babies can look very sick right away or only after a short delay.

1) “Classic” early-onset ACD/MPV.
Symptoms appear within hours of birth: severe low oxygen, fast breathing, and very high pressure in lung arteries. Standard treatments for newborn lung hypertension (extra oxygen, nitric oxide, high-frequency ventilation, even ECMO) bring little or only brief relief because the basic lung structure is wrong. PMC+1

2) Patchy or “atypical/late-onset” ACD/MPV.
Some babies have mixed areas—some lung regions are more normal, others are very abnormal. They may breathe reasonably for days or weeks, then suddenly worsen when stress, infection, or normal newborn changes raise demands on the lungs. These cases are often linked to FOXF1 changes as well and can be missed early. PMC+1

3) Genetic subtype by cause.

• FOXF1 coding variants (missense, nonsense, frameshift, splice) that alter the protein.

• FOXF1 whole-gene deletions.

• Deletions in a distant regulatory “enhancer” at chromosome 16q24.1 that switches FOXF1 on during lung development (these may spare the FOXF1 letters themselves but still silence the gene).

• Complex rearrangements in the FOXF1 region.
  Each of these is a “type” from the genetic point of view. Europe PMC+2PMC+2

4) Sporadic vs familial.
Most cases are new (“de novo”) in the child. Rarely, ACD/MPV runs in a family, sometimes showing effects of genomic imprinting (which parent passes the change can matter). Lippincott Journals+1

5) Isolated lung disease vs “ACD/MPV with other malformations.”
Because the same developmental program shapes other organs, some babies also have gut rotation problems, heart defects, kidney or spleen differences. PMC

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Causes

Note: “Causes” here means the root genetic or developmental reasons known to lead to ACD/MPV. Most are genetic and occur before birth.

1. Pathogenic missense variants in FOXF1 that change a key amino acid and disrupt the protein’s control of vessel development. PMC

2. Nonsense variants in FOXF1 that prematurely stop the protein (loss-of-function). PMC

3. Frameshift variants in FOXF1 that scramble the protein after small insertions/deletions. PMC

4. Splice-site variants in FOXF1 that mis-process the gene’s RNA. PMC

5. Whole-gene deletion of FOXF1 on chromosome 16q24.1. Europe PMC

6. Microdeletions in the distant FOXF1 enhancer (hundreds of kb away) that switch off FOXF1 despite an intact gene. PMC

7. Copy-number variants spanning the FOXF1 regulatory region (gain/loss altering gene dosage or control). PMC

8. Balanced or unbalanced chromosomal rearrangements that break the enhancer–promoter communication for FOXF1. Europe PMC

9. Parental mosaicism for a FOXF1 region change (present in some parent cells), passing the change to the child. (Reported in series and case reports.) PMC

10. De novo FOXF1 variants arising in the egg/sperm or early embryo without family history. Lippincott Journals

11. Imprinting effects near FOXF1 (parent-of-origin—paternal imprinting has been suggested), changing expression. Nature

12. Mutations that blunt FOXF1’s downstream signaling (e.g., disturbed STAT3 activity described for specific variants), impairing endothelial growth. ATS Journals

13. Long non-coding RNA disruption (e.g., LINC01081) within the enhancer neighborhood that modulates FOXF1 expression. BioMed Central

14. Chromatin/epigenetic defects in the 16q24.1 enhancer that reduce FOXF1 activation during lung development. PMC+1

15. Compound events (a coding variant plus a regulatory deletion) that together lower FOXF1 activity below a critical threshold. (Inferred from combined lesion reports.) PMC

16. Large regional deletions of the FOX gene cluster including FOXF1 and neighbors, producing ACD/MPV with extra malformations. Europe PMC

17. Regulatory sequence orientation changes (inversions) that separate FOXF1 from its enhancer. (Documented among structural variants in the locus.) PMC

18. Non-coding point variants in enhancer motifs that subtly reduce FOXF1 expression (rare but plausible mechanism described in locus studies). PMC

19. Unknown genetic causes—a meaningful minority have no identifiable change yet but fit clinically and pathologically; undiscovered genes or regulatory sites likely exist. PMC

20. Developmental field defects shared with other organs (same early signaling programs guide lung vessels, gut rotation, heart septation), explaining frequent associated anomalies—reflecting a common upstream cause. PMC

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Symptoms and signs

1. Severe trouble breathing soon after birth. The baby breathes fast and hard because oxygen cannot reach the blood well. Genetic Rare Disease Center

2. Blue or gray color (cyanosis). Skin, lips, or tongue look blue due to low oxygen. Genetic Rare Disease Center

3. Very low oxygen that does not improve with extra oxygen or usual newborn lung treatments. This mismatch is a key clue. PMC

4. Pulmonary hypertension (very high pressure in lung arteries). The right side of the heart must pump against high resistance. PMC

5. Poor response to inhaled nitric oxide. A typical therapy for newborn lung hypertension may help little or only briefly. PMC

6. Right-sided heart strain. The heart works too hard; echo may show right-ventricular pressure overload. PMC

7. Grunting, nasal flaring, chest retractions. Classic signs of respiratory distress. Genetic Rare Disease Center

8. Low blood pressure and poor perfusion. The baby may look pale and cool because oxygen delivery is inadequate. Genetic Rare Disease Center

9. Acidosis. Blood becomes too acidic due to poor oxygen and high carbon dioxide. Genetic Rare Disease Center

10. Feeding problems or vomiting. Sometimes due to associated intestinal malrotation or general instability. PMC

11. Abdominal distention. Can be related to gut anomalies or air trapping. PMC

12. Weakness or lethargy. Low oxygen affects the brain and muscles. Genetic Rare Disease Center

13. Late-onset worsening after days or weeks in atypical cases. A baby who seemed stable can deteriorate suddenly. PMC

14. Minimal or nonspecific chest-x-ray findings despite severe hypoxemia (another clue the architecture is wrong, not the air spaces alone). PMC

15. Features of other birth defects (heart, kidneys, bowel) in some babies because the same genes guide multiple organs. PMC

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Diagnostic tests

A) Physical examination (bedside observations)

1. General newborn exam focused on breathing effort. Doctors watch the rate, depth, grunting, flaring, and chest retractions. Severe, persistent distress within hours of birth raises concern for ACD/MPV when unresponsive to standard care. Genetic Rare Disease Center

2. Color and perfusion check. Cyanosis and prolonged capillary refill signal poor oxygen delivery. Lack of improvement with oxygen suggests a structural vascular problem. Genetic Rare Disease Center

3. Pre- and post-ductal oxygen saturation comparison. Measuring a hand (pre-ductal) and a foot (post-ductal) can show differences from ductal shunting; in ACD/MPV, saturations remain pathologically low overall despite oxygen. PMC

4. Cardiovascular examination. Right-sided heave, a loud second heart sound, or a tricuspid regurgitation murmur point to pulmonary hypertension rather than primary lung air-space disease. PMC

5. Abdominal exam for associated anomalies. Distention or abnormal bowel sounds can hint at malrotation or other GI anomalies often seen with FOXF1-region defects. PMC

B) Manual/bedside tests (simple, non-lab maneuvers)

6. Hyperoxia test. Giving 100% oxygen and checking whether PaO₂ rises as expected. In ACD/MPV, oxygenation often fails to improve adequately, unlike many other neonatal conditions. PMC

7. Gentle recruitment/ventilation trial under close monitoring. Failure of oxygenation to respond to careful adjustments (including high-frequency ventilation) suggests a structural microvascular problem rather than under-inflation alone. PMC

8. Bedside lung ultrasound. May show relatively nonspecific patterns compared with the severity of hypoxemia; useful to rule out pneumothorax or major consolidation while suspicion for ACD/MPV remains. SpringerOpen

9. Focused physical neurologic check. Signs of hypoxic injury or seizures can emerge from profound hypoxemia; while nonspecific, they underscore urgency. (Supportive clinical practice.) Genetic Rare Disease Center

10. Response to inhaled nitric oxide documented at bedside. Minimal or transient response supports ACD/MPV over reversible pulmonary vasoconstriction. PMC

C) Laboratory and pathological tests

11. Arterial blood gas (ABG). Shows severe, persistent hypoxemia with respiratory and/or metabolic acidosis despite high oxygen support. This pattern fits ACD/MPV when other causes are excluded. Genetic Rare Disease Center

12. Serum lactate. Elevated lactate reflects poor oxygen delivery to tissues; it tracks severity but is not specific. Genetic Rare Disease Center

13. Genetic testing: FOXF1 sequencing. Looks for single-letter or small insertion/deletion changes in the coding region and splice sites. Finding a pathogenic variant can confirm the diagnosis without lung biopsy. PMC+1

14. Deletion/duplication analysis of FOXF1. Detects whole-gene losses or gains (copy-number changes). Europe PMC

15. Chromosomal microarray or targeted array for 16q24.1. Finds microdeletions in the distant enhancer that turn FOXF1 on in fetal lung. These deletions are a well-proven cause of ACD/MPV. PMC+1

16. Broad exome/genome sequencing with CNV calling. Useful when initial tests are negative or when multiple anomalies suggest a larger structural change. PMC

17. Pathology of lung tissue (biopsy or autopsy). The “gold-standard” pattern shows too few capillaries away from the air–blood interface, thickened septa, small arteries with big muscular walls, misaligned small veins running with airways/arteries, and frequent lymphangiectasis. Risks of biopsy in unstable neonates are high, so many diagnoses are made post-mortem or via genetics. PMC+1

D) Electrodiagnostic and physiologic monitoring

18. Continuous pulse oximetry. Records persistently low oxygen saturations that resist improvement—an important monitoring clue. PMC

19. Electrocardiogram (ECG). May show right-ventricular strain or hypertrophy due to pulmonary hypertension. Not specific but supportive. PMC

20. Echocardiography with Doppler (physiologic imaging). Shows high pulmonary artery pressures, right-to-left shunts through the ductus arteriosus/foramen ovale, and usually no major structural heart disease to explain the severity, all of which point toward ACD/MPV when combined with the clinical picture. PMC

Non-pharmacological treatments (therapies and others)

These approaches support breathing, heart function, and family needs. They are not cures for classic ACD/MPV but can stabilize or bridge to decisions like transplant in selected infants, especially atypical cases. PMC

1. Gentle oxygen therapy – Give enough oxygen to keep saturations in an agreed target, avoiding oxidative injury. Purpose: improve oxygen content. Mechanism: increases alveolar oxygen, improving diffusion across available capillaries.

2. Optimized mechanical ventilation – Use lung-protective settings (appropriate PEEP, limited pressures). Purpose: avoid ventilator-induced lung injury. Mechanism: limits over-distension and shear while maintaining alveolar recruitment.

3. High-frequency ventilation (HFOV/HFJV) – Consider when conventional ventilation fails. Purpose: improve gas exchange at lower tidal volumes. Mechanism: rapid small breaths enhance oxygenation/CO₂ removal with minimal pressure swings.

4. Inhaled nitric oxide (iNO) trial with strict stop rules – May transiently raise oxygenation; discontinue if no clear benefit. Purpose: test reversibility of pulmonary vasoconstriction. Mechanism: selective pulmonary vasodilation; does not improve survival in classic ACD/MPV. PubMed

5. Prone or lateral positioning – Simple bedside method. Purpose: optimize ventilation-perfusion matching. Mechanism: redistributes blood flow and aeration.

6. Careful fluid and hemodynamic management – Avoid overload; ensure organ perfusion. Purpose: reduce pulmonary edema; support heart output. Mechanism: tailored fluids and inotrope guidance to keep right ventricle functioning.

7. Nutritional support (enteral/parenteral) with breast milk when possible – Purpose: support growth, immune function. Mechanism: provides calories, protein, micronutrients; human milk bioactives support immunity.

8. Temperature control and minimal handling – Purpose: reduce oxygen consumption and stress. Mechanism: stable thermoregulation lowers metabolic demand.

9. Infection prevention bundle – Purpose: reduce sepsis risk in fragile infants. Mechanism: hand hygiene, line care, ventilator bundles.

10. Early genetic counseling – Purpose: clarify diagnosis, recurrence risks, and testing for family. Mechanism: FOXF1 sequencing/CNV analysis; discuss mosaicism and prenatal options. PMC+1

11. Rapid diagnostic pathway – Purpose: shorten time to FOXF1 results and biopsy decision. Mechanism: targeted NGS panels/rapid exome; multidisciplinary review. laboratoryinvestigation.org

12. Open (or thoracoscopic) lung biopsy (when safe) – Purpose: histologic confirmation. Mechanism: shows reduced alveolar capillaries and misaligned veins. PMC

13. Extracorporeal membrane oxygenation (ECMO) – Veno-arterial/veno-venous support as bridge to decision or transplant in selected cases. Purpose: maintain oxygenation/circulation when lungs fail. Mechanism: bypass gas exchange and/or provide circulatory support. Current Challenges in Thoracic Surgery

14. Early referral to a pediatric lung-transplant center – Purpose: evaluate candidacy (especially atypical/milder phenotypes). Mechanism: transplant work-up, listing, and bridging strategies. PMC

15. ECMO-to-transplant protocols (awake/rehab when feasible) – Purpose: improve outcomes while awaiting organs. Mechanism: protocols for anticoagulation, mobility, infection prevention. Cleveland Clinic+1

16. Cardiac catheterization and echocardiography guidance – Purpose: assess PVR, heart function, and ductal flow; guide therapy. Mechanism: targeted hemodynamic data inform decisions.

17. Ethics and palliative care integration – Purpose: align care with family goals; manage symptoms; support decision-making. Mechanism: structured communication, comfort care pathways, bereavement support. Annals of Palliative Medicine

18. Transport to tertiary NICU – Purpose: access ECMO, transplant, and genetics teams. Mechanism: specialized retrieval and ventilation during transfer.

19. Comorbidity surgery (e.g., intestinal malrotation repair) when appropriate – Purpose: treat associated anomalies that threaten life or feeding. Mechanism: corrects GI obstruction/volvulus risk common in ACD/MPV cohorts. PMC

20. Family support, psychosocial care, and peer networks – Purpose: reduce stress and improve coping. Mechanism: social work, chaplaincy, ACDMPV family associations. chILD Foundation

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Drug treatments

There is no medication that “fixes” classic ACD/MPV. Many drugs below are used supportively for severe PPHN and right-heart strain. Some are off-label in neonates and must be dosed only by NICU specialists. iNO often gives only short-term oxygenation gains without survival benefit in classic ACD/MPV. Transplant remains the only definitive therapy for select cases. PubMed+1

(For safety here, I describe typical NICU practices in simple terms without giving prescriptive dosing instructions for your baby. Actual dosing is individualized by weight, organ function, and response.)

1. Inhaled Nitric Oxide (iNO) – Pulmonary vasodilator. Purpose: try to lower lung vessel resistance. Mechanism: raises cGMP in smooth muscle to dilate pulmonary arteries. Note: transient benefit common; no proven survival benefit in classic ACD/MPV. Side effects: methemoglobinemia, rebound PH if stopped abruptly. PubMed

2. Sildenafil (IV/oral) – PDE-5 inhibitor. Purpose: lower pulmonary pressure; sometimes used in atypical ACDMPV. Mechanism: preserves cGMP → vasodilation. Side effects: hypotension, GI upset. (Off-label in neonates; sometimes helpful in atypical cases.) molecularcasestudies.cshlp.org

3. Milrinone (IV) – PDE-3 inhibitor/inodilator. Purpose: improve right-ventricular function and reduce PVR. Mechanism: ↑cAMP → inotropy and vasodilation. Side effects: hypotension, arrhythmias.

4. Prostacyclin analogs (epoprostenol, iloprost, treprostinil) – Pulmonary vasodilators/antiproliferative. Purpose: reduce PVR and improve oxygenation. Mechanism: ↑cAMP, vasodilation; anti-remodeling. Side effects: systemic hypotension, bleeding risk. (Case-based use in NICU; evidence in classic ACD/MPV limited.)

5. Bosentan / macitentan – Endothelin-receptor antagonists. Purpose: reduce vasoconstriction. Mechanism: blocks endothelin-1 effects. Side effects: liver enzyme elevation, edema. (Off-label; considered in atypical or older presentations under PH expert care.) PubMed

6. Prostaglandin E1 (alprostadil) – Ductal patency agent. Purpose: keep ductus arteriosus open to offload the right heart. Mechanism: maintains R→L shunt to improve systemic output. Side effects: apnea, hypotension; ICU monitoring required.

7. Vasoactive infusions (dopamine, dobutamine, epinephrine, norepinephrine, vasopressin) – Hemodynamic support. Purpose: maintain blood pressure and coronary perfusion of the right ventricle. Mechanism: adrenergic/vasopressinergic receptor agonism. Side effects: arrhythmias, ischemia if overdosed.

8. Diuretics (furosemide) – Decongestant. Purpose: lessen pulmonary edema and RV volume load. Mechanism: diuresis via loop blockade. Side effects: electrolyte loss, ototoxicity (high doses).

9. Surfactant (poractant/beractant) – Alveolar surface tension reducer. Purpose: improve lung compliance if surfactant deficiency contributes. Mechanism: stabilizes alveoli. Side effects: transient desaturation, bradycardia during dosing.

10. Hydrocortisone (stress-dose when indicated) – Adrenal support/anti-inflammatory. Purpose: support blood pressure and reduce inflammation. Mechanism: glucocorticoid receptor effects. Side effects: hyperglycemia, infection risk.

11. Sedation/analgesia (fentanyl, morphine) and, if needed, neuromuscular blockade – Comfort and synchrony. Purpose: reduce oxygen demand, improve ventilator synchrony. Mechanism: opioid receptors; blockade prevents fighting the ventilator. Side effects: hypotension, ileus; prolonged use risks.

12. Empiric antibiotics (as indicated) – Sepsis coverage. Purpose: treat or prevent infections that worsen hypoxemia. Mechanism: pathogen-directed killing. Side effects: antibiotic-specific (renal, gut flora changes).

13. Inhaled bronchodilators (albuterol) for co-existing airway reactivity – Purpose: ease airflow obstruction. Mechanism: β2-agonism. Side effects: tachycardia, tremor.

14. Inhaled/IV prostacyclin during transport or ECMO – Purpose: targeted pulmonary vasodilation. Mechanism: see #4. Side effects: systemic hypotension.

15. Metabolic adjuncts (correct hypoglycemia, hypocalcemia, acidosis) – Purpose: stabilize hemodynamics. Mechanism: normalize cellular function; acidosis worsens PH.

16. Anticoagulation (heparin) during ECMO – Purpose: prevent circuit clotting. Mechanism: potentiates antithrombin. Side effects: bleeding.

17. Pulmonary hypertension combination therapy (specialist-directed) – Purpose: in atypical survivors or pre-transplant optimization. Mechanism: multi-pathway vasodilation/remodeling (PDE-5 + ERA ± prostacyclin). Side effects: additive hypotension, liver effects. PMC

18. Diuretic-sparing vasopressin strategy – Purpose: maintain blood pressure while limiting tachycardia/arrhythmia. Mechanism: V1-mediated vasoconstriction. Side effects: hyponatremia.

19. Inotropic support tailored to RV failure (e.g., epinephrine low-dose) – Purpose: support RV contractility. Mechanism: β-agonism. Side effects: arrhythmias, ↑O₂ demand.

20. Post-transplant immunosuppression (e.g., tacrolimus + steroids + antimetabolite) – Purpose: prevent rejection after lung transplant. Mechanism: T-cell inhibition. Side effects: infection risk, nephrotoxicity. (Transplant center protocols vary.) PMC

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Dietary molecular supplements

For newborns with ACD/MPV, no dietary supplement treats the core lung development problem. Feeding is typically human milk or specialized formulas under NICU nutrition support. Supplements below are general neonatal/parental nutrition considerations, not disease-modifying treatments; all require clinician approval.

1. Vitamin D (infant standard 400 IU/day when enteral feeds established) – Function: bone/immune support. Mechanism: vitamin D receptor modulation.

2. DHA/ARA (via human milk or fortified formula) – Function: brain/retina support. Mechanism: membrane PUFA incorporation.

3. Choline (maternal/fortified sources) – Function: cell membranes and methylation. Mechanism: phosphatidylcholine synthesis.

4. Iron (when indicated) – Function: hemoglobin production. Mechanism: supports oxygen carriage.

5. Zinc (if deficient) – Function: growth and immunity. Mechanism: enzymatic cofactor.

6. Sodium/Calcium/Phosphate (as prescribed) – Function: growth/mineral balance. Mechanism: electrolyte homeostasis.

7. Protein fortifiers for breast milk – Function: adequate calories/protein for healing. Mechanism: increased nitrogen supply.

8. Medium-chain triglycerides (MCT) when malabsorption suspected – Function: calorie dense, easier absorption. Mechanism: portal transport independent of bile acids.

9. Probiotics (only if NICU policy allows) – Function: gut microbiome support. Mechanism: colonization resistance; data vary.

10. Prenatal/parental nutrition optimization – Function: supports maternal recovery and milk quality. Mechanism: meets micronutrient needs.

(Avoid any unapproved herbal or “immune booster” products in infants.)

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Immunity-booster / Regenerative / Stem-cell drugs

There are no approved immune boosters, regenerative drugs, or stem-cell therapies for treating ACD/MPV. Below are research directions being explored for congenital and neonatal lung disorders; none are standard of care for ACD/MPV.

1. Mesenchymal stromal cell (MSC) therapy (investigational for BPD) – Proposed paracrine repair; clinical research only.

2. Ex vivo lung bioengineering and decellularized scaffolds – Future transplant alternatives; experimental.

3. iPSC-derived alveolar/endothelial cells – Disease modeling and potential cell replacement; preclinical.

4. Targeted gene therapy/editing of FOXF1/enhancer – Theoretically address root cause; no clinical application yet. BioMed Central+1

5. Small-molecule modulators of vascular development – Anti-remodeling concepts; not validated in ACD/MPV.

6. Endothelial progenitor cell infusions – Investigational vascular repair; preclinical/early research.

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Surgeries / procedures

1. Open (or thoracoscopic) lung biopsy – Procedure: remove a small lung piece for pathology. Why: confirm ACD/MPV when diagnosis will change management. PMC

2. ECMO cannulation (VA or VV) – Procedure: place large cannulas to run extracorporeal support. Why: bridge to decision or transplant evaluation in selected infants failing maximal therapy. Current Challenges in Thoracic Surgery

3. Bilateral lung transplantation – Procedure: replace both lungs with donor lungs. Why: only definitive option for survival in select atypical/milder presentations; reported 5-year survival comparable to other infant indications at experienced centers. PMC

4. Repair of associated anomalies (e.g., Ladd’s procedure for malrotation) – Procedure: correct GI malrotation. Why: reduce volvulus risk and improve feeding outcomes in infants who are candidates for ongoing care. PMC

5. Tracheostomy (selected atypical survivors) – Procedure: surgical airway for long-term ventilation. Why: facilitates chronic support when prolonged ventilation is needed (rare scenarios).

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Preventions

• We cannot prevent classic ACD/MPV because it forms during early lung development, often from de novo FOXF1 alterations. National Organization for Rare Disorders
  What families can do:

1. Genetic counseling after a case is diagnosed; discuss FOXF1 testing and future pregnancy options. PMC

2. Prenatal testing in future pregnancies if a familial variant is known; consider targeted testing. PMC

3. High-risk obstetric care with planned delivery at a tertiary center.

4. Avoid teratogens and smoking during pregnancy; follow prenatal vitamins per obstetrician.

5. Maternal vaccinations (per guidelines) to reduce infections that complicate neonatal care.

6. Early recognition of refractory PPHN in the newborn to trigger rapid work-up. Genetic Rare Disease Center

7. Infection-prevention bundles in NICU (line care, hand hygiene).

8. Careful ventilator strategies to avoid added lung injury.

9. Timely transfer to a center with ECMO and pediatric transplant.

10. Family support planning to help decision-making under stress.

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When to see doctors (red flags)

For newborns: immediately seek emergency care if you see fast breathing, grunting, chest retractions, blueness (cyanosis), poor feeding, or sleepiness. In hospitals, if a baby has PPHN that does not improve within the first 1–2 weeks or keeps needing very high oxygen or iNO levels, clinicians should consider disorders like ACD/MPV and call specialized centers. SAGE Journals

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What to eat and what to avoid

• For infants: feeding plans are individualized in NICU. Human milk is preferred when possible. Avoid unapproved herbal products, honey (until after 1 year), and any supplements not prescribed by the team.

• For lactating parents: eat a balanced diet; limit alcohol; avoid smoking and recreational drugs; follow doctor-approved medications only.
  (Nutrition supports health but cannot correct the underlying lung development problem in ACD/MPV.)

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Frequently Asked Questions

1. Is ACD/MPV the same as PPHN?
   No. PPHN is a physiology (high lung blood pressure). ACD/MPV is a structural lung development disorder that causes refractory PPHN. PMC

2. What gene is involved?
   Most cases involve FOXF1 or its distant enhancer on 16q24.1. PubMed+1

3. How is it diagnosed?
   By genetic testing (FOXF1 sequencing/CNV) and, when needed and safe, lung biopsy showing reduced capillaries and misaligned veins. PMC+1

4. Does inhaled nitric oxide cure it?
   No. iNO may transiently improve oxygenation but does not improve survival in classic ACD/MPV. PubMed

5. Can babies recover without transplant?
   Most classic cases are fatal despite support. A small group with atypical/milder ACD/MPV can live longer and may respond to pulmonary vasodilators or undergo transplant with outcomes similar to other infant transplants. PMC

6. Is it inherited?
   Usually sporadic (de novo); rare familial cases and parental mosaicism exist. Genetic counseling is recommended. PMC+1

7. Are other organs affected?
   Sometimes. GI malformations (e.g., malrotation) and other anomalies can occur. PMC

8. Does early diagnosis help?
   Yes. It guides decisions about ECMO, biopsy, palliative care, and transplant referral. Rapid FOXF1 testing can shorten time to diagnosis. laboratoryinvestigation.org

9. What is ECMO’s role?
   ECMO can stabilize babies as a bridge to decision or bridge to transplant in selected cases but cannot fix the underlying problem. Current Challenges in Thoracic Surgery

10. What are transplant outcomes?
    In reported U.S. series, 5-year survival around ~56% for transplanted ACD/MPV infants—similar to other infant lung transplant indications at experienced centers. PMC

11. Can prenatal ultrasound detect it?
    There are no specific ultrasound signs that reliably diagnose ACD/MPV, but genetic testing can identify many cases when a familial variant is known; biopsy remains the gold standard postnatally if needed. PMC

12. Are there clinical trials?
    Trials are rare due to disease rarity; research focuses on FOXF1 biology, genetics, and transplant strategies. BioMed Central

13. What about stem-cell therapy?
    Not available for ACD/MPV outside research; no approved regenerative drug. (See research section above.)

14. Can diet or vitamins cure it?
    No. Nutrition supports growth but does not repair lung development defects.

15. What support is available for families?
    Specialist NICU teams, genetics services, palliative care, and family organizations like ACD Association provide education and connection. chILD Foundation

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: September 14, 2025.

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