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VACTERL with hydrocephalus

MedGen UID:
376400
Concept ID:
C1848599
Disease or Syndrome
Synonyms: VACTERL association with hydrocephalus; VACTERL-H
Modes of inheritance:
Autosomal recessive inheritance
MedGen UID:
141025
Concept ID:
C0441748
Intellectual Product
Source: Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in individuals with two pathogenic alleles, either homozygotes (two copies of the same mutant allele) or compound heterozygotes (whereby each copy of a gene has a distinct mutant allele).
X-linked recessive inheritance
MedGen UID:
375779
Concept ID:
C1845977
Finding
Source: Orphanet
A mode of inheritance that is observed for recessive traits related to a gene encoded on the X chromosome. In the context of medical genetics, X-linked recessive disorders manifest in males (who have one copy of the X chromosome and are thus hemizygotes), but generally not in female heterozygotes who have one mutant and one normal allele.
 
Monarch Initiative: MONDO:0010172
OMIM®: 276950
Orphanet: ORPHA3412

Definition

VACTERL describes a constellation of congenital anomalies, including vertebral anomalies, anal atresia, congenital cardiac disease, tracheoesophageal fistula, renal anomalies, radial dysplasia, and other limb defects; see 192350. Cases of familial VACTERL with hydrocephalus (H) have been reported with suggestion of autosomal recessive or X-linked inheritance (see 314390). Other patients thought to have VACTERL-H, including 2 unrelated infants reported by Porteous et al. (1992), had been found to have Fanconi anemia (see 227650). Porteous et al. (1992) suggested that chromosomal breakage studies should be performed in all cases of VACTERL/VACTERL-H to rule out Fanconi anemia. Alter et al. (2007) noted that a VATER phenotype had been reported in Fanconi anemia of complementation groups A (227650), C (227645), D1 (605724), E (600901), F (603467), and G (614082). X-linked VACTERL-H is also associated with mutations in the FANCB gene (300515). [from OMIM]

Clinical features

From HPO
Renal hypoplasia
MedGen UID:
120571
Concept ID:
C0266295
Congenital Abnormality
Hypoplasia of the kidney.
Absent thumb
MedGen UID:
480441
Concept ID:
C3278811
Finding
Absent thumb, i.e., the absence of both phalanges of a thumb and the associated soft tissues.
Radial club hand
MedGen UID:
870951
Concept ID:
C4025414
Congenital Abnormality
Wrist is bent inward toward the thumb because of a congenital defect associated with shortening or absence of the radius.
Abnormal heart morphology
MedGen UID:
6748
Concept ID:
C0018798
Congenital Abnormality
Any structural anomaly of the heart.
Abnormal cardiovascular system morphology
MedGen UID:
892473
Concept ID:
C4049796
Anatomical Abnormality
Any structural anomaly of the heart and blood vessels.
Imperforate anus
MedGen UID:
1997
Concept ID:
C0003466
Congenital Abnormality
Congenital absence of the anus, i.e., the opening at the bottom end of the intestinal tract.
Hydrocephalus
MedGen UID:
9335
Concept ID:
C0020255
Disease or Syndrome
Hydrocephalus is an active distension of the ventricular system of the brain resulting from inadequate passage of CSF from its point of production within the cerebral ventricles to its point of absorption into the systemic circulation.
Aqueductal stenosis
MedGen UID:
75614
Concept ID:
C0266476
Congenital Abnormality
Stenosis of the cerebral aqueduct (also known as the mesencephalic duct, aqueductus mesencephali, or aqueduct of Sylvius), which connects the third cerebral ventricle in the diencephalon to the fourth ventricle, which is between the pons and cerebellum.
Abnormal vertebral morphology
MedGen UID:
371742
Concept ID:
C1834129
Anatomical Abnormality
An abnormality of one or more of the vertebrae.
Abnormality of the vertebral column
MedGen UID:
892426
Concept ID:
C4021789
Anatomical Abnormality
Any abnormality of the vertebral column.
Respiratory insufficiency
MedGen UID:
11197
Concept ID:
C0035229
Pathologic Function
Impairment of gas exchange within the lungs secondary to a disease process, neoplasm, or trauma, possibly resulting in hypoxia, hypercarbia, or both, but not requiring intubation or mechanical ventilation. Patients are normally managed with pharmaceutical therapy, supplemental oxygen, or both.
Respiratory failure
MedGen UID:
257837
Concept ID:
C1145670
Disease or Syndrome
A severe form of respiratory insufficiency characterized by inadequate gas exchange such that the levels of oxygen or carbon dioxide cannot be maintained within normal limits.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVVACTERL with hydrocephalus

Professional guidelines

PubMed

Altintas B, Giri N, McReynolds LJ, Best A, Alter BP
Haematologica 2023 Jan 1;108(1):69-82. doi: 10.3324/haematol.2021.279981. PMID: 35417938Free PMC Article

Recent clinical studies

Etiology

Altintas B, Giri N, McReynolds LJ, Best A, Alter BP
Haematologica 2023 Jan 1;108(1):69-82. doi: 10.3324/haematol.2021.279981. PMID: 35417938Free PMC Article
Fouda MA, Kim TY, Cohen AR
World Neurosurg 2022 Mar;159:48-53. Epub 2021 Dec 22 doi: 10.1016/j.wneu.2021.12.062. PMID: 34954057
Alter BP, Giri N
Am J Med Genet A 2016 Jun;170(6):1520-4. Epub 2016 Mar 30 doi: 10.1002/ajmg.a.37637. PMID: 27028275
Evans JA, Vitez M, Czeizel A
Am J Med Genet 1994 Jan 1;49(1):52-66. doi: 10.1002/ajmg.1320490111. PMID: 8172251
Evans JA, Stranc LC, Kaplan P, Hunter AG
Am J Med Genet 1989 Oct;34(2):177-82. doi: 10.1002/ajmg.1320340209. PMID: 2816994

Diagnosis

Fouda MA, Kim TY, Cohen AR
World Neurosurg 2022 Mar;159:48-53. Epub 2021 Dec 22 doi: 10.1016/j.wneu.2021.12.062. PMID: 34954057
Boer LL, Morava E, Klein WM, Schepens-Franke AN, Oostra RJ
Birth Defects Res 2017 Jun 1;109(10):791-804. Epub 2017 May 16 doi: 10.1002/bdr2.1049. PMID: 28509418
Chen CP, Chang TY, Chen YY, Chern SR, Su JW, Wang W
Taiwan J Obstet Gynecol 2013 Dec;52(4):575-9. doi: 10.1016/j.tjog.2013.10.022. PMID: 24411047
Solomon BD
Orphanet J Rare Dis 2011 Aug 16;6:56. doi: 10.1186/1750-1172-6-56. PMID: 21846383Free PMC Article
Lomas FE, Dahlstrom JE, Ford JH
Am J Med Genet 1998 Feb 26;76(1):74-8. doi: 10.1002/(sici)1096-8628(19980226)76:1<74::aid-ajmg14>3.0.co;2-m. PMID: 9508070

Therapy

Dracopoulos C, Gembicki M, Scharf JL, Welp A, Berg N, Weichert J
Fetal Pediatr Pathol 2022 Oct;41(5):871-880. Epub 2021 Oct 23 doi: 10.1080/15513815.2021.1994068. PMID: 34689682
Pasquier L, Marcorelles P, Loget P, Pelluard F, Carles D, Perez MJ, Bendavid C, de La Rochebrochard C, Ferry M, David V, Odent S, Laquerrière A
Acta Neuropathol 2009 Feb;117(2):185-200. Epub 2008 Dec 5 doi: 10.1007/s00401-008-0469-9. PMID: 19057916
Herman TE, Siegel MJ
J Perinatol 2002 Sep;22(6):496-8. doi: 10.1038/sj.jp.7210765. PMID: 12168129

Prognosis

Ishak GE, Dempsey JC, Shaw DW, Tully H, Adam MP, Sanchez-Lara PA, Glass I, Rue TC, Millen KJ, Dobyns WB, Doherty D
Brain 2012 May;135(Pt 5):1370-86. Epub 2012 Mar 26 doi: 10.1093/brain/aws065. PMID: 22451504Free PMC Article
McCauley J, Masand N, McGowan R, Rajagopalan S, Hunter A, Michaud JL, Gibson K, Robertson J, Vaz F, Abbs S, Holden ST
Am J Med Genet A 2011 Oct;155A(10):2370-80. Epub 2011 Sep 9 doi: 10.1002/ajmg.a.33913. PMID: 21910217
Solomon BD
Orphanet J Rare Dis 2011 Aug 16;6:56. doi: 10.1186/1750-1172-6-56. PMID: 21846383Free PMC Article
Herman TE, Siegel MJ
J Perinatol 2002 Sep;22(6):496-8. doi: 10.1038/sj.jp.7210765. PMID: 12168129
Evans JA, Stranc LC, Kaplan P, Hunter AG
Am J Med Genet 1989 Oct;34(2):177-82. doi: 10.1002/ajmg.1320340209. PMID: 2816994

Clinical prediction guides

Boer LL, Morava E, Klein WM, Schepens-Franke AN, Oostra RJ
Birth Defects Res 2017 Jun 1;109(10):791-804. Epub 2017 May 16 doi: 10.1002/bdr2.1049. PMID: 28509418
Kitova TT, Kitov B, Milkov D, Gaigi S
Fetal Pediatr Pathol 2014 Aug;33(4):239-43. Epub 2014 May 16 doi: 10.3109/15513815.2014.915366. PMID: 24833489
McCauley J, Masand N, McGowan R, Rajagopalan S, Hunter A, Michaud JL, Gibson K, Robertson J, Vaz F, Abbs S, Holden ST
Am J Med Genet A 2011 Oct;155A(10):2370-80. Epub 2011 Sep 9 doi: 10.1002/ajmg.a.33913. PMID: 21910217
Friedland-Little JM, Hoffmann AD, Ocbina PJ, Peterson MA, Bosman JD, Chen Y, Cheng SY, Anderson KV, Moskowitz IP
Hum Mol Genet 2011 Oct 1;20(19):3725-37. Epub 2011 Jun 8 doi: 10.1093/hmg/ddr241. PMID: 21653639Free PMC Article
Froster UG, Wallner SJ, Reusche E, Schwinger E, Rehder H
Am J Med Genet 1996 Mar 15;62(2):169-72. doi: 10.1002/(SICI)1096-8628(19960315)62:2<169::AID-AJMG10>3.0.CO;2-M. PMID: 8882398

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