Tag: visualeditor-wikitext |
|
| (4 intermediate revisions by the same user not shown) |
| Line 1: |
Line 1: |
| {{Use dmy dates|date=November 2017}}
| |
| {{Use American English|date=November 2017}}
| |
| {{short description|Rare lung disease, present at birth and treatable by lung transplants}} | | {{short description|Rare lung disease, present at birth and treatable by lung transplants}} |
| {{Infobox medical condition (new) | | {{Infobox medical condition (new) |
| | name = Alveolar capillary dysplasia | | | name = Alveolar capillary dysplasia |
| | synonyms = Alveolar capillary dysplasia with misalignment of pulmonary veins (ACDMPV) | | | synonyms = Alveolar capillary dysplasia with misalignment of pulmonary veins (ACDMPV) |
| | image =
| | | pronounce = |
| | thumb =
| | | field = [[Pediatric pulmonology]], [[neonatology]], [[medical genetics]] |
| | alt =
| | | symptoms = [[Cyanosis]] (blue lips or skin), [[tachypnea]] (rapid breathing), hypoxemia, respiratory distress, poor feeding, failure to respond to oxygen therapy |
| | caption =
| | | complications = [[Respiratory failure]], hypoxia, multiorgan dysfunction, death |
| | pronounce = | | | onset = Typically within the first 24 to 48 hours after birth |
| | field = | | | duration = Rapidly progressive without intervention |
| | symptoms = [[cyanosis|Blue lips or skin]], [[tachypnea|rapid breathing]]<ref name="Bishop2011"/> | | | types = Classic (early-onset), atypical (late or focal onset) |
| | complications = [[Respiratory failure]]<ref name="Bishop2011"/> | | | causes = Mutation or deletion involving the ''[[FOXF1]]'' gene or regulatory region |
| | onset = 24-48 hours after birth<ref name="Bishop2011">{{cite journal|last1=Bishop|first1=Naomi B.|last2=Stankiewicz|first2=Pawel|last3=Steinhorn|first3=Robin H.|title=Alveolar Capillary Dysplasia|journal=American Journal of Respiratory and Critical Care Medicine|date=15 July 2011|volume=184|issue=2|pages=172–179|doi=10.1164/rccm.201010-1697CI|pmid=21471096|pmc=3172887}}</ref> | | | risks = Sporadic mutation; rare familial cases; possible association with other congenital anomalies (especially cardiac, gastrointestinal, and urogenital malformations) |
| | duration = | | | diagnosis = Clinical presentation, [[lung biopsy]], [[genetic testing]] for ''FOXF1'' mutations |
| | types = | | | differential = [[Persistent pulmonary hypertension of the newborn]] (PPHN), [[sepsis]], [[pneumonia]], [[surfactant deficiencies]], [[hyaline membrane disease]], [[pulmonary hypoplasia]], [[acinar dysplasia]], [[congenital alveolar dysplasia]] |
| | causes = ''[[FOXF1]]'' mutation (at least 40% of cases)<ref name="Bishop2011"/> | | | prevention = None currently known |
| | risks = | | | treatment = Supportive care, [[extracorporeal membrane oxygenation]] (ECMO), [[lung transplant]] (only definitive treatment) |
| | diagnosis = Lung biopsy or ''FOXF1'' genetic testing<ref name="Bishop2011"/><ref name ="Nogee2017">{{cite journal|last1=Nogee|first1=Lawrence M.|title=Interstitial lung disease in newborns|journal=Seminars in Fetal and Neonatal Medicine|date=August 2017|volume=22|issue=4|pages=227–233|doi=10.1016/j.siny.2017.03.003|pmid=28363760|pmc=5537026}}</ref> | | | medication = Pulmonary vasodilators (e.g., [[inhaled nitric oxide]], [[sildenafil]]), inotropic support, mechanical ventilation |
| | differential = [[Persistent fetal circulation|Idiopathic PPHN]], [[sepsis]], [[pneumonia]], [[surfactant deficiency|surfactant deficiencies]], [[hyaline membrane disease]], [[pulmonary hypoplasia]], [[acinar dysplasia]], [[congenital alveolar dysplasia]]<ref name="Bishop2011"/> | | | prognosis = Poor; extremely high mortality rate in the neonatal period without lung transplant |
| | prevention = None<ref name="Bishop2011"/> | | | frequency = Rare; exact incidence unknown |
| | treatment = Lung transplant<ref name="Bishop2011"/> | | | deaths = Nearly universal without transplant in severe cases |
| | medication = Pulmonary vasodilators | |
| | prognosis = Mortality rate ~100%<ref name="Bishop2011"/> | |
| | frequency = Unknown<ref name="Bishop2011"/> | |
| | deaths = | |
| }} | | }} |
| <!-- Definition and symptoms -->
| |
| '''Alveolar capillary dysplasia''' (ACD) is a rare, [[birth defect|congenital]] [[interstitial lung disease|diffuse lung disease]] characterized by abnormal [[blood vessels]] in the [[lungs]] that cause [[pulmonary hypertension|highly elevated pulmonary blood pressure]] and an inability to effectively [[breathing|oxygenate]] and remove [[carbon dioxide]] from the blood. ACD typically presents in newborn babies within hours of birth as [[tachypnea|rapid]] and [[respiratory distress|labored]] [[breathing]], [[cyanosis|blue-colored lips or skin]], quickly leading to [[respiratory failure]] and death. Atypical forms of ACD have been reported with initially milder symptoms and survival of many months before the onset of respiratory failure or [[lung transplantation]].
| |
|
| |
|
| <!-- Cause and mechanism -->
| | '''Alveolar capillary dysplasia''' (ACD) is a rare and serious congenital disorder characterized by the abnormal development of the capillary vascular system within the [[lungs]]. This condition leads to severe [[pulmonary hypertension]] and respiratory distress in newborns, often resulting in early neonatal death. |
| Most cases of ACD are caused by [[mutation]]s affecting the [[gene]] ''[[FOXF1]]'' or its nearby [[enhancer (genetics)|enhancer]] region.<ref name="Szafranaski2016">{{cite journal|last1=Szafranski|first1=Przemyslaw|last2=Gambin|first2=Tomasz|last3=Dharmadhikari|first3=Avinash V.|display-authors=et al|title=Pathogenetics of alveolar capillary dysplasia with misalignment of pulmonary veins|journal=Human Genetics|date=12 April 2016|volume=135|issue=5|pages=569–586|doi=10.1007/s00439-016-1655-9|pmid=27071622|pmc=5518754}}</ref> Exactly how these mutations lead to abnormal lung development is unknown. Abnormal lung development is characterized by thickened [[pulmonary alveolus|alveolar]] interstitium, misplacement of pulmonary capillaries away from the alveolar surface, and fewer capillaries overall. This results in poor gas exchange and pulmonary hypertension.<ref name="Bishop2011"/> There is evidence for connections between pulmonary arteries and systemic vessels, which would additionally contribute to poor blood oxygenation.<ref name="Galambos2015">{{cite journal|last1=Galambos|first1=Csaba|last2=Sims-Lucas|first2=Sunder|last3=Ali|first3=Noorjahan|display-authors=et al|title=Intrapulmonary vascular shunt pathways in alveolar capillary dysplasia with misalignment of pulmonary veins|journal=Thorax|date=January 2015|volume=70|issue=1|pages=84–85|doi=10.1136/thoraxjnl-2014-205851|pmid=25052575|pmc=4405163}}</ref>
| |
|
| |
|
| <youtube>
| | ==Pathophysiology== |
| title='''{{PAGENAME}}'''
| | Alveolar capillary dysplasia is primarily a developmental disorder of the [[pulmonary vasculature]]. In normal lung development, the [[alveoli]] are closely associated with a rich network of capillaries, facilitating efficient gas exchange. In ACD, there is a malformation of the capillary bed, where the capillaries are either absent or improperly aligned with the alveoli. This misalignment prevents adequate oxygenation of the blood, leading to [[hypoxemia]] and [[respiratory failure]]. |
| movie_url=http://www.youtube.com/v/aBkxzkzQOf8
| |
| &rel=1
| |
| embed_source_url=http://www.youtube.com/v/aBkxzkzQOf8
| |
| &rel=1
| |
| wrap = yes
| |
| width=750
| |
| height=600
| |
| </youtube>
| |
|
| |
|
| <!-- Diagnosis and Treatment -->
| | ==Genetics== |
| ACD is typically diagnosed by examination of lung tissue under a [[microscope]], either from lung [[biopsy]] or an [[autopsy]]. The characteristic findings of misplaced pulmonary veins adjacent to pulmonary arteries, and abnormal alveolar and capillary development confirm the diagnosis.<ref name="Bishop2011" /> ''FOXF1'' genetic testing is also available, which can confirm the diagnosis without invasive testing.<ref name ="Nogee2017" /> There are no effective treatments for severe ACD. Standard therapy, which includes [[mechanical ventilation]], pulmonary [[vasodilators]], and possibly [[ECMO]], provide only temporary improvement in symptoms with disease progression returning within hours. For babies with atypical ACD, response to medical therapy is more sustained, lasting for several months. For those that can be stabilized, definitive treatment is bilateral lung transplantation.<ref name="Bishop2011" /> | | ACD is often associated with genetic mutations, particularly in the [[FOXF1]] gene located on chromosome 16. Mutations in this gene disrupt normal lung development, leading to the characteristic features of ACD. The condition can occur sporadically or be inherited in an autosomal dominant pattern, although familial cases are rare. |
|
| |
|
| <!-- Epidemiology and History -->
| | ==Clinical Presentation== |
| ACD is a rare disease. About 100 cases have been reported.<ref name="Bishop2011" /> The first case was reported in 1981.<ref name ="Janney1981">{{cite journal|last1=Janney|first1=CG|last2=Askin|first2=FB|last3=Kuhn C|first3=3rd|title=Congenital alveolar capillary dysplasia--an unusual cause of respiratory distress in the newborn.|journal=American Journal of Clinical Pathology|date=November 1981|volume=76|issue=5|pages=722–7|pmid=7293984|doi=10.1093/ajcp/76.5.722}}</ref>
| | Newborns with alveolar capillary dysplasia typically present with severe respiratory distress shortly after birth. Symptoms include rapid breathing ([[tachypnea]]), [[cyanosis]], and difficulty maintaining adequate oxygen levels despite supplemental oxygen therapy. The condition is often resistant to conventional treatments for pulmonary hypertension. |
| | |
| ==Signs and symptoms==
| |
| ACD is a congenital disease whose symptoms appear within hours to days after birth. Babies with ACD usually have no symptoms at the time of birth, but soon after will begin to breathe rapidly, showing increased work of breathing, and may have blue discoloration around the lips, arms, or legs, especially when feeding or crying. If an [[echocardiogram]] is performed, marked [[cardiomegaly|thickening]] of the [[right ventricle]] will be seen, resulting from highly elevated pulmonary blood pressure. ACD is generally resistant to treatment. Babies who have persistent symptoms that are poorly relieved by standard therapies for neonatal pulmonary hypertension is commonly observed in ACD.<ref name="Bishop2011"/>
| |
| | |
| Atypical forms of ACD have been reported with only mildly rapid breathing shortly after birth. They may present with the above symptoms of ACD at several months of age. Their symptoms may improve with standard pulmonary hypertension therapies for weeks to months before symptoms return.<ref name="Bishop2011"/>
| |
| | |
| Babies born with ACD usually have other congenital abnormalities affecting the [[heart]], the [[intestines]], [[urinary system]], or [[genitals]].<ref name="Bishop2011"/>
| |
| | |
| ==Cause==
| |
| Most cases of ACD are caused by [[deletion (genetics)|deletions]] or [[point mutations]] involving the [[gene]] ''[[FOXF1]]'' on [[chromosome 16]] or an area near the ''FOXF1'' gene that regulates its [[gene expression|expression]]. ACD is an [[autosomal dominant disorder]], meaning only one disease-causing mutation affecting ''FOXF1'' or its regulator region is needed to cause ACD. Evidence strongly suggests that the ''FOXF1'' regulatory region is [[genomic imprinting|imprinted]], which might affect disease severity and may permit some to [[genetic carrier|carry]] the disease with few or no symptoms.<ref name="Szafranaski2016" />
| |
| | |
| ==Mechanism==
| |
| How mutations affecting ''FOXF1'' or its regulatory region cause ACD is unknown. ACD-causing mutations result in abnormal development of lung vasculature and alveoli. In ACD, the interstitium of alveoli is thickened, with few to no [[capillaries]] located at the alveolar surface to perform [[gas exchange]], and with lower capillary density overall. This reduction in capillaries and their misplacement away from the alveolar surface result in poor oxygenation and retention of carbon dioxide in the blood and high pulmonary blood pressure.<ref name="Bishop2011" /> There is also evidence of direct connections between pulmonary arteries and systemic vessels, which would deliver deoxygenated blood to the body, also contributing to low blood oxygenation.<ref name="Galambos2015" />
| |
| | |
| Another characteristic [[histology|histologic]] finding is the presence of a [[pulmonary vein]] located next to a [[pulmonary artery]] and [[bronchus]] in the same bronchovascular bundle. In a normal lung, the pulmonary vein courses with lymphatic vessels in the lung septa.
| |
|
| |
|
| ==Diagnosis== | | ==Diagnosis== |
| The gold standard for ACD diagnosis is by examination of lung tissue under a microscope. The diagnosis is made if the pathologist sees the characteristic findings of ACD: misplaced pulmonary veins adjacent to pulmonary arteries, abnormal alveoli with thickened interstitia and abnormal capillary development. Due to the rapidly progressive course of ACD, this diagnosis is frequently made during [[autopsy]]. If ACD is suspected early, examination of tissue from lung biopsy results in the quickest diagnosis.<ref name="Bishop2011" /> Genetic testing for ''FOXF1'' is now available and can allow for slower but non-invasive diagnosis. As not all disease-causing mutations are known, false negatives or results of uncertain significance are possible with genetic testing.<ref name ="Nogee2017" /> | | The diagnosis of ACD is challenging and often requires a high index of suspicion. It is typically confirmed through a combination of clinical presentation, imaging studies, and histopathological examination of lung tissue. A lung biopsy revealing the characteristic absence or misalignment of capillaries is definitive for diagnosis. Genetic testing can also identify mutations in the FOXF1 gene, supporting the diagnosis. |
|
| |
|
| There are no characteristic pattern of routine lab results or imaging findings that allow definitive diagnosis of ACD.<ref name="Bishop2011" /> | | ==Management== |
| | There is currently no cure for alveolar capillary dysplasia, and management is primarily supportive. Treatment focuses on alleviating symptoms and may include mechanical ventilation, administration of [[nitric oxide]] to reduce pulmonary hypertension, and extracorporeal membrane oxygenation (ECMO) in severe cases. Lung transplantation has been considered in some cases, but the rarity and severity of the condition make it a challenging option. |
|
| |
|
| ==Treatment== | | ==Prognosis== |
| Initial treatments attempt to improve low blood oxygenation and high pulmonary blood pressures. Because blood oxygen content is usually very low, babies with ACD are often [[intubated]], [[sedated]], and mechanically ventilated with pure oxygen. Pulmonary vasodilators like [[sildenafil]] or inhaled [[nitric oxide]] can be used to reduce pulmonary blood pressures.<ref name="pmid9021581">{{cite journal|vauthors = Kitayama Y, Kamata S, Okuyama H, Usui N, Sawai T, Kobayashi T, Fukui Y, Okada A|title = Nitric oxide inhalation therapy for an infant with persistent pulmonary hypertension caused by misalignment of pulmonary veins with alveolar capillary dysplasia|journal = Journal of Pediatric Surgery|volume = 32|issue = 1|pages = 99–100|date = January 1997|pmid = 9021581|doi = 10.1016/s0022-3468(97)90105-6|url = |issn = }}</ref> For those with severe ACD, these measures offer only momentary improvement. As symptoms worsen, ECMO can be used, but it also offers only brief improvement. There are no effective treatments for severe ACD.<ref name="Bishop2011" />
| | The prognosis for infants with ACD is generally poor, with most affected newborns succumbing to the condition within the first few weeks of life. Early diagnosis and supportive care can improve outcomes, but the overall survival rate remains low. |
|
| |
|
| For infants with atypical ACD who initially had milder symptoms and present at months of life, there can be better response to therapy. There have been reports of infants with ACD surviving to 20 or 36 months without lung transplantation. Bilateral lung transplantation may be the definitive treatment.
| | ==Related pages== |
| | | * [[Pulmonary hypertension]] |
| ==Epidemiology== | | * [[Respiratory distress syndrome]] |
| ACD is a rare disease. As of 2011, about 100 cases had been reported. It is likely an under-recognized cause of death shortly after birth because diagnosis requires microscopic examination of lung tissue or specialized genetic testing, or death can be attributed to severe heart or intestinal congenital abnormalities which frequently occur in ACD.<ref name="Bishop2011" />
| | * [[Congenital disorders]] |
| | | * [[Genetic mutations]] |
| ==History==
| |
| [[Congenital alveolar dysplasia]] was first described by MacMahon in 1948.<ref name="pmid18874417">{{cite journal| author = MacMahon HE| title = Congenital alveolar dysplasia of the lungs| journal = The American Journal of Pathology| volume = 24| issue = 4| pages = 919–31|date=July 1948| pmid = 18874417| pmc = 1942746| doi = | url = | issn = }}</ref><ref name="pmid18874463">{{cite journal| author = MacMahon HE| title = Congenital alveolar dysplasia; a developmental anomaly involving pulmonary alveoli| journal = Pediatrics| volume = 2| issue = 1| pages = 43–57|date=July 1948| pmid = 18874463| doi = | url = | issn = }}</ref> | |
| The seminal case first describing ACD was by Janney and colleagues in 1981.<ref name ="Janney1981" /> Transmission from a [[genetic carrier|carrier]] parent to a child was first reported in 1994.<ref name="pmid8283361">{{cite journal| vauthors = Boggs S, Harris MC, Hoffman DJ, Goel R, McDonald-McGinn D, Langston C, Zackai E, Ruchelli E| title = Misalignment of pulmonary veins with alveolar capillary dysplasia: affected siblings and variable phenotypic expression| journal = The Journal of Pediatrics| volume = 124| issue = 1| pages = 125–8|date=January 1994| pmid = 8283361| doi = 10.1016/S0022-3476(94)70267-5| url = | issn = }}</ref>
| |
| | |
| {{rarediseases}}
| |
|
| |
|
| == External links == | | == External links == |
| Line 102: |
Line 66: |
| | Orphanet = 210122 | | | Orphanet = 210122 |
| }} | | }} |
|
| |
| {{Transcription factor/coregulator deficiencies}} | | {{Transcription factor/coregulator deficiencies}} |
| | | {{rarediseases}} |
| [[Category:Rare diseases]] | | [[Category:Rare diseases]] |
| [[Category:Lung disorders]] | | [[Category:Lung disorders]] |
| [[Category:Pediatrics]] | | [[Category:Pediatrics]] |
| | [[Category:Congenital disorders]] |
| | [[Category:Respiratory diseases]] |
| | [[Category:Genetic disorders]] |
Rare lung disease, present at birth and treatable by lung transplants
| Alveolar capillary dysplasia
|
| [[File:|250px|alt=|]]
|
| Synonyms
|
Alveolar capillary dysplasia with misalignment of pulmonary veins (ACDMPV)
|
| Pronounce
|
|
| Field
|
Pediatric pulmonology, neonatology, medical genetics
|
| Symptoms
|
Cyanosis (blue lips or skin), tachypnea (rapid breathing), hypoxemia, respiratory distress, poor feeding, failure to respond to oxygen therapy
|
| Complications
|
Respiratory failure, hypoxia, multiorgan dysfunction, death
|
| Onset
|
Typically within the first 24 to 48 hours after birth
|
| Duration
|
Rapidly progressive without intervention
|
| Types
|
Classic (early-onset), atypical (late or focal onset)
|
| Causes
|
Mutation or deletion involving the FOXF1 gene or regulatory region
|
| Risks
|
Sporadic mutation; rare familial cases; possible association with other congenital anomalies (especially cardiac, gastrointestinal, and urogenital malformations)
|
| Diagnosis
|
Clinical presentation, lung biopsy, genetic testing for FOXF1 mutations
|
| Differential diagnosis
|
Persistent pulmonary hypertension of the newborn (PPHN), sepsis, pneumonia, surfactant deficiencies, hyaline membrane disease, pulmonary hypoplasia, acinar dysplasia, congenital alveolar dysplasia
|
| Prevention
|
None currently known
|
| Treatment
|
Supportive care, extracorporeal membrane oxygenation (ECMO), lung transplant (only definitive treatment)
|
| Medication
|
Pulmonary vasodilators (e.g., inhaled nitric oxide, sildenafil), inotropic support, mechanical ventilation
|
| Prognosis
|
Poor; extremely high mortality rate in the neonatal period without lung transplant
|
| Frequency
|
Rare; exact incidence unknown
|
| Deaths
|
Nearly universal without transplant in severe cases
|
Alveolar capillary dysplasia (ACD) is a rare and serious congenital disorder characterized by the abnormal development of the capillary vascular system within the lungs. This condition leads to severe pulmonary hypertension and respiratory distress in newborns, often resulting in early neonatal death.
Pathophysiology[edit]
Alveolar capillary dysplasia is primarily a developmental disorder of the pulmonary vasculature. In normal lung development, the alveoli are closely associated with a rich network of capillaries, facilitating efficient gas exchange. In ACD, there is a malformation of the capillary bed, where the capillaries are either absent or improperly aligned with the alveoli. This misalignment prevents adequate oxygenation of the blood, leading to hypoxemia and respiratory failure.
Genetics[edit]
ACD is often associated with genetic mutations, particularly in the FOXF1 gene located on chromosome 16. Mutations in this gene disrupt normal lung development, leading to the characteristic features of ACD. The condition can occur sporadically or be inherited in an autosomal dominant pattern, although familial cases are rare.
Clinical Presentation[edit]
Newborns with alveolar capillary dysplasia typically present with severe respiratory distress shortly after birth. Symptoms include rapid breathing (tachypnea), cyanosis, and difficulty maintaining adequate oxygen levels despite supplemental oxygen therapy. The condition is often resistant to conventional treatments for pulmonary hypertension.
Diagnosis[edit]
The diagnosis of ACD is challenging and often requires a high index of suspicion. It is typically confirmed through a combination of clinical presentation, imaging studies, and histopathological examination of lung tissue. A lung biopsy revealing the characteristic absence or misalignment of capillaries is definitive for diagnosis. Genetic testing can also identify mutations in the FOXF1 gene, supporting the diagnosis.
Management[edit]
There is currently no cure for alveolar capillary dysplasia, and management is primarily supportive. Treatment focuses on alleviating symptoms and may include mechanical ventilation, administration of nitric oxide to reduce pulmonary hypertension, and extracorporeal membrane oxygenation (ECMO) in severe cases. Lung transplantation has been considered in some cases, but the rarity and severity of the condition make it a challenging option.
Prognosis[edit]
The prognosis for infants with ACD is generally poor, with most affected newborns succumbing to the condition within the first few weeks of life. Early diagnosis and supportive care can improve outcomes, but the overall survival rate remains low.
Related pages[edit]
External links[edit]
Lua error: bad argument #2 to 'title.new' (unrecognized namespace name 'Portal').
| Genetic disorders relating to deficiencies of transcription factor or coregulators |
| (1) Basic domains | |
(2) Zinc finger
DNA-binding domains | |
| (3) Helix-turn-helix domains | |
(4) β-Scaffold factors
with minor groove contacts | |
| (0) Other transcription factors | |
|
NIH genetic and rare disease info[edit]
Alveolar capillary dysplasia is a rare disease.
| Rare and genetic diseases |
|
Rare diseases - Alveolar capillary dysplasia
| A-Z list of rare diseases | |
| Also see | |
| Resources | |
|
