Alveolar capillary dysplasia

Alveolar capillary dysplasia
Classification and external resources
OMIM	265380

Alveolar capillary dysplasia (ACD, also congenital alveolar dysplasia) is a very rare congenital malformation involving abnormal development of the capillary vascular system around the alveoli of the lungs. It is a rare cause of persistent pulmonary hypertension in infants.^[1] It also may be a rare cause of pulmonary hypoplasia.^[2]

Babies with ACD may appear normal at birth but within minutes or hours they develop respiratory distress with persistent pulmonary hypertension.^[3] ACD does not respond to standard therapies that resolve simple pulmonary hypertension. The lack of response is an important diagnostic clue.

Cause

Two broad types of genetic abnormality have been found to cause ACDMPV: (1) a mutation of the FOXF1 gene on chromosome 16, or (2) other genetic abnormalities such as deletions in areas of chromosome 16 that regulate the expression of the FOXF1 gene. New genetic abnormalities are being found regularly, but at present around 80-90% of infants with confirmed ACDMPV can be found to have one of these abnormalities. The genetic abnormalities responsible for ACDMPV in the remaining 10-20% of cases are currently being investigated including testing for deletions farther away from the FOXF1 gene on chromosome 16 and whole exome testing.^[4]

Diagnosis

ACD commonly is diagnosed postmortem, by a pathologist.

Sometimes ACD is diagnosed clinically.^[5] This is common when there is a family history of ACD, but rare otherwise. A clinical differential diagnosis of ACD excludes fetal atelectasis.^[3]

ACD is not detectable by prenatal imaging. However, some babies with ACD have associated congenital malformations that are detectable by imaging. The identification of genes involved in ACD offers the potential for prenatal testing and genetic counseling.

Treatment

Most babies with ACD have normal Apgar scores at 1 and 5 minutes, but within minutes or hours present with hypoxia and upon investigation are found to have hypoxemia and pulmonary hypertension. Initial treatments address the hypoxia, usually beginning with supplemental oxygen and arrangements for urgent transport to a neonatal intensive care unit.

Therapies that have been tried to extend life include extracorporeal membrane oxygenation and nitric oxide. These are supportive therapies for persistent pulmonary hypertension; they do not treat the ACD. The objective of therapy is to keep the baby alive long enough to obtain a lung transplant.^[6]

Research

Baylor College of Medicine in Houston, Texas has conducted ACD research since 2001.

Advance in experimental treatment

Several patients have survived with atypical or “patchy ACDMPV” long enough to receive lung transplants. According to a 2013 case series conducted by St. Louis Children’s Hospital, four ACDMPV patients (ages 4 months, 5 months, 9 months and 20 months of age at time of transplant) with atypical presentations of ACDMPV each underwent a successful bilateral lung transplantation (BLT). As stated in the case study, “If they survive to BLT, patients with ACDMPV can have successful outcomes” and the ACDMPV patients “are alive at last follow-up at 1, 8, 9 and 12 years of age” (as of May 2013).^[7]

According to the St. Louis Children's Hospital (the Level I pediatric trauma center and pediatric teaching hospital for the Washington University School of Medicine), which is noted worldwide for its record in pediatric pulmonary transplantation, a type of artificial lung device, the Quadrox, was used after ECMO as a bridge to a dual lung transplant in ten-month-old Eleni Scott of the St. Louis suburb of Florissant, Missouri, who after transplantation returned to her home. Doctors have said it is too early to presume it will continue to work here or work in other pediatric patients as an experiment, much less a successful, curative standard therapy, but the infant has survived thus far, meaning that there might be hope for sufferers of this rare condition. For more information, please see the link to the news release.^[8]

History

ACD was first described in 1948.^[3]^[9] A familial association of ACD/MPV was first reported in 1994.^[10]

References

↑ Cater G, Thibeault DW, Beatty EC, Kilbride HW, Huntrakoon M (February 1989). "Misalignment of lung vessels and alveolar capillary dysplasia: a cause of persistent pulmonary hypertension". The Journal of Pediatrics 114 (2): 293–300. doi:10.1016/S0022-3476(89)80800-5. PMID 2915290.
↑ Sirkin W, O'Hare BP, Cox PN, Perrin D, Cutz E, Silver MM (1997). "Alveolar capillary dysplasia: lung biopsy diagnosis, nitric oxide responsiveness, and bronchial generation count". Pediatric Pathology & Laboratory Medicine : Journal of the Society for Pediatric Pathology, Affiliated with the International Paediatric Pathology Association 17 (1): 125–32. doi:10.3109/15513819709168352. PMID 9050066.
1 2 3 MacMahon HE (July 1948). "Congenital alveolar dysplasia of the lungs". The American Journal of Pathology 24 (4): 919–31. PMC 1942746. PMID 18874417.
↑ Stankiewicz P, Sen P, Bhatt SS, Storer M, Xia Z, Bejjani BA, Ou Z, Wiszniewska J, Driscoll DJ, Bolivar J, Bauer M, Zackai EH, McDonald-McGinn D, Nowaczyk MM, Murray M, Shaikh TH, Martin V, Tyreman M, Simonic I, Willatt L, Paterson J, Mehta S, Rajan D, Fitzgerald T, Gribble S, Prigmore E, Patel A, Shaffer LG, Carter NP, Cheung SW, Langston C, Shaw-Smith C (June 2009). "Genomic and genic deletions of the FOX gene cluster on 16q24.1 and inactivating mutations of FOXF1 cause alveolar capillary dysplasia and other malformations". American Journal of Human Genetics 84 (6): 780–91. doi:10.1016/j.ajhg.2009.05.005. PMC 2694971. PMID 19500772.
↑ Liet JM, Joubert M, Gournay V, Godon N, Godde F, Nomballais MF, Roze JC (January 1998). "[Neonatal hypoxemia due to misaligned pulmonary vessels with alveolar capillary dysplasia]". Archives de Pédiatrie (in French) 5 (1): 27–30. doi:10.1016/s0929-693x(97)83463-x. PMID 10223108.
↑ Kitayama Y, Kamata S, Okuyama H, Usui N, Sawai T, Kobayashi T, Fukui Y, Okada A (January 1997). "Nitric oxide inhalation therapy for an infant with persistent pulmonary hypertension caused by misalignment of pulmonary veins with alveolar capillary dysplasia". Journal of Pediatric Surgery 32 (1): 99–100. doi:10.1016/s0022-3468(97)90105-6. PMID 9021581.
↑ White, F., S. Sweet, R. M. Grady, A. Faro, P. Michelson, P. Eghtesady, U. Boston et al. (2013): In: Am J Respir Crit Care Med 187 (2013): A2251.
↑ http://www.stlouischildrens.org/articles/features/2012/new-medical-approach-helps-baby-with-rare-disease
↑ MacMahon HE (July 1948). "Congenital alveolar dysplasia; a developmental anomaly involving pulmonary alveoli". Pediatrics 2 (1): 43–57. PMID 18874463.
↑ Boggs S, Harris MC, Hoffman DJ, Goel R, McDonald-McGinn D, Langston C, Zackai E, Ruchelli E (January 1994). "Misalignment of pulmonary veins with alveolar capillary dysplasia: affected siblings and variable phenotypic expression". The Journal of Pediatrics 124 (1): 125–8. doi:10.1016/S0022-3476(94)70267-5. PMID 8283361.

External links

"ACD Association: "Searching for answers...hoping for a cure."".

Genetic disorder, protein biosynthesis: Transcription factor/coregulator deficiencies

(1) Basic domains

1.2	Feingold syndrome Saethre–Chotzen syndrome

1.3	Tietz syndrome

(2) Zinc finger
DNA-binding domains

2.1	(Intracellular receptor): Thyroid hormone resistance Androgen insensitivity syndrome PAIS MAIS CAIS Kennedy's disease PHA1AD pseudohypoaldosteronism Estrogen insensitivity syndrome X-linked adrenal hypoplasia congenita MODY 1 Familial partial lipodystrophy 3 SF1 XY gonadal dysgenesis

2.2	Barakat syndrome Tricho–rhino–phalangeal syndrome

2.3	Greig cephalopolysyndactyly syndrome/Pallister–Hall syndrome Denys–Drash syndrome Duane-radial ray syndrome MODY 7 MRX 89 Townes–Brocks syndrome Acrocallosal syndrome Myotonic dystrophy 2

2.5	Autoimmune polyendocrine syndrome type 1

(3) Helix-turn-helix domains

3.1	ARX Ohtahara syndrome Lissencephaly X2 MNX1 Currarino syndrome HOXD13 SPD1 Synpolydactyly PDX1 MODY 4 LMX1B Nail–patella syndrome MSX1 Tooth and nail syndrome OFC5 PITX2 Axenfeld syndrome 1 POU4F3 DFNA15 POU3F4 DFNX2 ZEB1 Posterior polymorphous corneal dystrophy Fuchs' dystrophy 3 ZEB2 Mowat–Wilson syndrome

3.2	PAX2 Papillorenal syndrome PAX3 Waardenburg syndrome 1&3 PAX4 MODY 9 PAX6 Gillespie syndrome Coloboma of optic nerve PAX8 Congenital hypothyroidism 2 PAX9 STHAG3

3.3	FOXC1 Axenfeld syndrome 3 Iridogoniodysgenesis, dominant type FOXC2 Lymphedema–distichiasis syndrome FOXE1 Bamforth–Lazarus syndrome FOXE3 Anterior segment mesenchymal dysgenesis FOXF1 ACD/MPV FOXI1 Enlarged vestibular aqueduct FOXL2 Premature ovarian failure 3 FOXP3 IPEX

3.5	IRF6 Van der Woude syndrome Popliteal pterygium syndrome

(4) β-Scaffold factors
with minor groove contacts

4.2	Hyperimmunoglobulin E syndrome

4.3	Holt–Oram syndrome Li–Fraumeni syndrome Ulnar–mammary syndrome

4.7	Campomelic dysplasia MODY 3 MODY 5 SF1 SRY XY gonadal dysgenesis Premature ovarian failure 7 SOX10 Waardenburg syndrome 4c Yemenite deaf-blind hypopigmentation syndrome

4.11	Cleidocranial dysostosis

(0) Other transcription factors

0.6	Kabuki syndrome

Ungrouped

Transcription coregulators

Coactivator:	CREBBP Rubinstein–Taybi syndrome

Corepressor:	HR (Atrichia with papular lesions)

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