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Diaphragmatic hernia 4, with cardiovascular defects(DIH4)

MedGen UID:
1823983
Concept ID:
C5774210
Disease or Syndrome
Synonym: DIH4
 
Gene (location): ALDH1A2 (15q21.3)
 
Monarch Initiative: MONDO:0859571
OMIM®: 620025

Definition

Diaphragmatic hernia-4 with cardiovascular defects (DIH4) is an autosomal recessive congenital anomaly syndrome characterized by the presence of diaphragmatic hernia or eventration apparent at birth. Affected infants have associated pulmonary hypoplasia and respiratory insufficiency resulting in death in infancy. Most also have variable cardiovascular defects, including aortopulmonary window or conotruncal anomalies. Dysmorphic facial features and mild distal limb anomalies are sometimes observed (Beecroft et al., 2021). For a discussion of genetic heterogeneity of congenital diaphragmatic hernia (CDH), see DIH1 (142340). [from OMIM]

Clinical features

From HPO
Cryptorchidism
MedGen UID:
8192
Concept ID:
C0010417
Congenital Abnormality
Cryptorchidism, or failure of testicular descent, is a common human congenital abnormality with a multifactorial etiology that likely reflects the involvement of endocrine, environmental, and hereditary factors. Cryptorchidism can result in infertility and increases risk for testicular tumors. Testicular descent from abdomen to scrotum occurs in 2 distinct phases: the transabdominal phase and the inguinoscrotal phase (summary by Gorlov et al., 2002).
Clubfoot
MedGen UID:
3130
Concept ID:
C0009081
Congenital Abnormality
Clubfoot is a congenital limb deformity defined as fixation of the foot in cavus, adductus, varus, and equinus (i.e., inclined inwards, axially rotated outwards, and pointing downwards) with concomitant soft tissue abnormalities (Cardy et al., 2007). Clubfoot may occur in isolation or as part of a syndrome (e.g., diastrophic dysplasia, 222600). Clubfoot has been reported with deficiency of long bones and mirror-image polydactyly (Gurnett et al., 2008; Klopocki et al., 2012).
Finger syndactyly
MedGen UID:
65139
Concept ID:
C0221352
Congenital Abnormality
Webbing or fusion of the fingers, involving soft parts only or including bone structure. Bony fusions are referred to as "bony" Syndactyly if the fusion occurs in a radio-ulnar axis. Fusions of bones of the fingers in a proximo-distal axis are referred to as "Symphalangism".
Clinodactyly of the 5th finger
MedGen UID:
340456
Concept ID:
C1850049
Congenital Abnormality
Clinodactyly refers to a bending or curvature of the fifth finger in the radial direction (i.e., towards the 4th finger).
2-3 toe syndactyly
MedGen UID:
1645640
Concept ID:
C4551570
Congenital Abnormality
Syndactyly with fusion of toes two and three.
Aortopulmonary window
MedGen UID:
365
Concept ID:
C0003516
Congenital Abnormality
A congenital anomaly with an abnormal connection between the aorta and the main pulmonary artery resulting in an aortopulmonary shunt.
Ventricular septal defect
MedGen UID:
42366
Concept ID:
C0018818
Congenital Abnormality
A hole between the two bottom chambers (ventricles) of the heart. The defect is centered around the most superior aspect of the ventricular septum.
Pulmonary artery hypoplasia
MedGen UID:
75585
Concept ID:
C0265910
Congenital Abnormality
Underdevelopment of the pulmonary artery.
Aortic root aneurysm
MedGen UID:
720712
Concept ID:
C1298820
Anatomical Abnormality
An abnormal localized widening (dilatation) of the aortic root.
Pulmonary arterial hypertension
MedGen UID:
425404
Concept ID:
C2973725
Disease or Syndrome
Pulmonary hypertension is defined mean pulmonary artery pressure of 25mmHg or more and pulmonary capillary wedge pressure of 15mmHg or less when measured by right heart catheterisation at rest and in a supine position.
Aortopulmonary collateral arteries
MedGen UID:
1633176
Concept ID:
C4703564
Anatomical Abnormality
Small ectopic arteries or arterial branches that connect the aorta, aortic branches and/or subclavian artery regions directly to the lung parenchyma, usually seen in conjunction with pulmonary atresia, ventricular septal defect (VSD) and/or closed ductus arteriosus.
Hepatomegaly
MedGen UID:
42428
Concept ID:
C0019209
Finding
Abnormally increased size of the liver.
Low-set ears
MedGen UID:
65980
Concept ID:
C0239234
Congenital Abnormality
Upper insertion of the ear to the scalp below an imaginary horizontal line drawn between the inner canthi of the eye and extending posteriorly to the ear.
Diaphragmatic eventration
MedGen UID:
8359
Concept ID:
C0011981
Congenital Abnormality
A congenital failure of muscular development of part or all of one or both hemidiaphragms, resulting in superior displacement of abdominal viscera and altered lung development.
Micrognathia
MedGen UID:
44428
Concept ID:
C0025990
Congenital Abnormality
Developmental hypoplasia of the mandible.
Coronal cleft vertebrae
MedGen UID:
320483
Concept ID:
C1834954
Finding
Frontal schisis (cleft or cleavage) of vertebral bodies.
11 pairs of ribs
MedGen UID:
326950
Concept ID:
C1839731
Finding
Presence of only 11 pairs of ribs.
Macrocephaly
MedGen UID:
745757
Concept ID:
C2243051
Finding
Occipitofrontal (head) circumference greater than 97th centile compared to appropriate, age matched, sex-matched normal standards. Alternatively, a apparently increased size of the cranium.
Aplasia of the left hemidiaphragm
MedGen UID:
1680550
Concept ID:
C5194758
Finding
Congenital absence of the left half of the diaphragm.
Pulmonary hypoplasia
MedGen UID:
78574
Concept ID:
C0265783
Congenital Abnormality
A congenital abnormality in which the lung parenchyma is not fully developed. It may be associated with other congenital abnormalities.
Neonatal respiratory distress
MedGen UID:
924182
Concept ID:
C4281993
Finding
Respiratory difficulty as newborn.
Recurrent infections
MedGen UID:
65998
Concept ID:
C0239998
Finding
Increased susceptibility to infections.
Webbed neck
MedGen UID:
113154
Concept ID:
C0221217
Congenital Abnormality
Pterygium colli is a congenital skin fold that runs along the sides of the neck down to the shoulders. It involves an ectopic fibrotic facial band superficial to the trapezius muscle. Excess hair-bearing skin is also present and extends down the cervical region well beyond the normal hairline.
Bulbous nose
MedGen UID:
66013
Concept ID:
C0240543
Finding
Increased volume and globular shape of the anteroinferior aspect of the nose.
Downslanted palpebral fissures
MedGen UID:
98391
Concept ID:
C0423110
Finding
The palpebral fissure inclination is more than two standard deviations below the mean.
Short chin
MedGen UID:
784514
Concept ID:
C3697248
Finding
Decreased vertical distance from the vermilion border of the lower lip to the inferior-most point of the chin.
Polyhydramnios
MedGen UID:
6936
Concept ID:
C0020224
Pathologic Function
The presence of excess amniotic fluid in the uterus during pregnancy.
Optic nerve hypoplasia
MedGen UID:
137901
Concept ID:
C0338502
Disease or Syndrome
Underdevelopment of the optic nerve.

Professional guidelines

PubMed

Fick TA, Scott DA, Lupo PJ, Weigand J, Morris SA
Cardiol Young 2022 Apr;32(4):550-557. Epub 2021 Jul 2 doi: 10.1017/S1047951121002535. PMID: 34210367Free PMC Article
Balkin EM, Olson ED, Robertson L, Adatia I, Fineman JR, Keller RL
Pediatr Cardiol 2016 Apr;37(4):756-64. Epub 2016 Feb 3 doi: 10.1007/s00246-016-1347-1. PMID: 26843461Free PMC Article
Krasemann T
Fetal Diagn Ther 2008;23(4):249; author reply 249. Epub 2008 Apr 11 doi: 10.1159/000127418. PMID: 18417987

Recent clinical studies

Etiology

Renik-Jankowska W, Buczyńska A, Sidorkiewicz I, Kosiński P, Zbucka-Krętowska M
Biochim Biophys Acta Mol Basis Dis 2024 Apr;1870(4):167105. Epub 2024 Feb 28 doi: 10.1016/j.bbadis.2024.167105. PMID: 38428682
Bojanić K, Pritišanac E, Luetić T, Vuković J, Sprung J, Weingarten TN, Schroeder DR, Grizelj R
J Pediatr Surg 2015 Nov;50(11):1817-22. Epub 2015 Jul 14 doi: 10.1016/j.jpedsurg.2015.07.004. PMID: 26259558
Shiono N, Inamura N, Takahashi S, Nagata K, Fujino Y, Hayakawa M, Usui N, Okuyama H, Kanamori Y, Taguchi T, Minakami H
Pediatr Int 2014 Aug;56(4):553-8. Epub 2014 May 30 doi: 10.1111/ped.12322. PMID: 24612014
Rychik J, Tian Z, Cohen MS, Ewing SG, Cohen D, Howell LJ, Wilson RD, Johnson MP, Hedrick HL, Flake AW, Crombleholme TM, Adzick NS
Circulation 2004 Sep 21;110(12):1549-56. Epub 2004 Sep 7 doi: 10.1161/01.CIR.0000142294.95388.C4. PMID: 15353490
Bollmann R, Kalache K, Mau H, Chaoui R, Tennstedt C
Fetal Diagn Ther 1995 Jan-Feb;10(1):52-9. doi: 10.1159/000264193. PMID: 7710680

Diagnosis

Renik-Jankowska W, Buczyńska A, Sidorkiewicz I, Kosiński P, Zbucka-Krętowska M
Biochim Biophys Acta Mol Basis Dis 2024 Apr;1870(4):167105. Epub 2024 Feb 28 doi: 10.1016/j.bbadis.2024.167105. PMID: 38428682
Fick TA, Scott DA, Lupo PJ, Weigand J, Morris SA
Cardiol Young 2022 Apr;32(4):550-557. Epub 2021 Jul 2 doi: 10.1017/S1047951121002535. PMID: 34210367Free PMC Article
Fraser CD 3rd, Hill KD, Wallace A, Chiswell K, Zhou X, Jelin EB, Kays D, Jacobs JP, Hibino N, Jacobs ML, Vricella LA
Semin Thorac Cardiovasc Surg 2019 Spring;31(1):69-77. Epub 2018 Sep 27 doi: 10.1053/j.semtcvs.2018.09.014. PMID: 30267752
Lin AE, Pober BR, Mullen MP, Slavotinek AM
Am J Med Genet A 2005 Dec 15;139(3):186-93. doi: 10.1002/ajmg.a.31023. PMID: 16283673
Bollmann R, Kalache K, Mau H, Chaoui R, Tennstedt C
Fetal Diagn Ther 1995 Jan-Feb;10(1):52-9. doi: 10.1159/000264193. PMID: 7710680

Therapy

Fraser CD 3rd, Hill KD, Wallace A, Chiswell K, Zhou X, Jelin EB, Kays D, Jacobs JP, Hibino N, Jacobs ML, Vricella LA
Semin Thorac Cardiovasc Surg 2019 Spring;31(1):69-77. Epub 2018 Sep 27 doi: 10.1053/j.semtcvs.2018.09.014. PMID: 30267752
Jawaid WB, Qasem E, Jones MO, Shaw NJ, Losty PD
Br J Surg 2013 Dec;100(13):1833-7. doi: 10.1002/bjs.9306. PMID: 24227372
Groth SS, Whitson BA, D'Cunha J, Andrade RS, Maddaus MA
J Thorac Cardiovasc Surg 2008 Jan;135(1):38-43. doi: 10.1016/j.jtcvs.2007.09.017. PMID: 18179916
Bielinska M, Jay PY, Erlich JM, Mannisto S, Urban Z, Heikinheimo M, Wilson DB
Ann Med 2007;39(4):261-74. doi: 10.1080/07853890701326883. PMID: 17558598Free PMC Article
Rychik J, Tian Z, Cohen MS, Ewing SG, Cohen D, Howell LJ, Wilson RD, Johnson MP, Hedrick HL, Flake AW, Crombleholme TM, Adzick NS
Circulation 2004 Sep 21;110(12):1549-56. Epub 2004 Sep 7 doi: 10.1161/01.CIR.0000142294.95388.C4. PMID: 15353490

Prognosis

Bojanić K, Pritišanac E, Luetić T, Vuković J, Sprung J, Weingarten TN, Schroeder DR, Grizelj R
J Pediatr Surg 2015 Nov;50(11):1817-22. Epub 2015 Jul 14 doi: 10.1016/j.jpedsurg.2015.07.004. PMID: 26259558
Takahashi S, Sago H, Kanamori Y, Hayakawa M, Okuyama H, Inamura N, Fujino Y, Usui N, Taguchi T
Pediatr Int 2013 Aug;55(4):492-7. doi: 10.1111/ped.12104. PMID: 23565971
Rychik J, Tian Z, Cohen MS, Ewing SG, Cohen D, Howell LJ, Wilson RD, Johnson MP, Hedrick HL, Flake AW, Crombleholme TM, Adzick NS
Circulation 2004 Sep 21;110(12):1549-56. Epub 2004 Sep 7 doi: 10.1161/01.CIR.0000142294.95388.C4. PMID: 15353490
Allan LD, Irish MS, Glick PL
Clin Perinatol 1996 Dec;23(4):795-812. PMID: 8982572
Bollmann R, Kalache K, Mau H, Chaoui R, Tennstedt C
Fetal Diagn Ther 1995 Jan-Feb;10(1):52-9. doi: 10.1159/000264193. PMID: 7710680

Clinical prediction guides

Starr LJ, Lindsay ME, Lino Cardenas CL, Yetman AT
Am J Med Genet A 2023 Mar;191(3):786-793. Epub 2022 Dec 30 doi: 10.1002/ajmg.a.63075. PMID: 36584339
Bojanić K, Pritišanac E, Luetić T, Vuković J, Sprung J, Weingarten TN, Schroeder DR, Grizelj R
J Pediatr Surg 2015 Nov;50(11):1817-22. Epub 2015 Jul 14 doi: 10.1016/j.jpedsurg.2015.07.004. PMID: 26259558
Takahashi S, Sago H, Kanamori Y, Hayakawa M, Okuyama H, Inamura N, Fujino Y, Usui N, Taguchi T
Pediatr Int 2013 Aug;55(4):492-7. doi: 10.1111/ped.12104. PMID: 23565971
Allan LD, Irish MS, Glick PL
Clin Perinatol 1996 Dec;23(4):795-812. PMID: 8982572
Fogel M, Copel JA, Cullen MT, Hobbins JC, Kleinman CS
Am J Perinatol 1991 Nov;8(6):411-6. doi: 10.1055/s-2007-999427. PMID: 1839950

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