congenital diaphragmatic hernia

Congenital diaphragmatic hernia occurs about once in each 3,000 newborns and is associated with a 30 to 60% mortality rate with significant morbidity among survivors.

The pathologic consequences of CDH result from the abdominal contents entering the thoracic cavity. Hypoplasia of the lung due to decreased thoracic volume compromises pulmonary capacity and often results in neonatal death.

Types

 paravertebral type or posterolateral type (Bochdalek type) (80%)
 parasternal type (in the foramen of Morgagni)
 hiatal hernia (4.5%)
 diaphragmatic agenesis (1/250 000 births)
 diaphragmatic eventration
 central diaphragmatic hernia (septum transversum)

• Central CDH occurs in the midline of the septum transversum and accounts for 1 to 2% of the total cases of CDH.

Localization

 left diaphragmatic hernia
 right diaphragmatic hernia
 bilateral diaphragmatic hernia

Etiology

 non-syndromic congenital diaphragmatic hernia

• familial forms of CDH (6993337)

 syndromic congenital diaphragmatic hernia

• Fryns syndrome
• Cornelia de Lange syndrome (#MIM.122470#)
• congenital epidermolysis bullosa with diaphragmatic hernia (MIM.226735)
• Beckwith-Wiedemann syndrome (15517831)
• Brachman-de Lange syndrome
• Donnai syndrome
• Denys-Drash syndrome
• WAGR syndrome (15779010)
• Perlman syndrome
• germline mutations in STRA6-associated syndrome (STRA6 mutations)(17273977)

Cytogenetics (chromosomal anomalies in 15%)

 2q terminal deletion (15386475)
 interstitial deletion of chromosome 3 (11494969)
 Wolf-Hirschhorn syndrome (4p-) (16903248, 16498629)
 de novo deletions of 8p23.1 (16700088, 15255033)
 complete trisomy 9 (15229846)
 tetrasomy 9p (16226972)
 del(8)(p23.1) (15255033, 15937941)
 +i(12)(p10)[6]/46XX[14] (Pallister-Killian syndrome)(15255033)

 15q26 anomalies (16252246, 15750894, 15539876)

• 15q26 deletion (16700088)
• 15q26 unbalanced translocations (15057983, 15539876)
• ring chromosome 15 (17380471)

 18p- syndrome (14755475)
 trisomy 18 (15906414, 12428693)

 translocations

• der(22)t(11:22) (q23.3:q11.2) (15255033)
• t(X;2)(p22;q23)
• der(14)t(1;14)(q11;p11)

Animal models

 Knock-out mice

• SLIT3 KO mice (MIM.603745) (9693030)

Associations

 pulmonary anomalies

• pulmonary hypoplasia
• extralobar sequestration
• tracheoesophageal fistula
• congenital pulmonary airway malformations

 cardiovascular anomalies

• tetralogy of Fallot
• endocardial cushion defect
• atrial septal defects
• ventricular septal defects
• ectopia cordis
• aortic coarctation
• pulmonic stenosis

 gastrointestinal anomalies

• imperforate anus
• omphalocele
• pyloric stenosis
• gastric duplication
• intestinal malrotation

 genitourinary anomalies

• hydronephrosis
• multicystic kidney
• duplicated collecting system

 polymalformative syndrome

• Cornelia de Lange syndrome
• fetal alcohol syndrome
• trisomy 18
• trisomy 21
• monosomy X (Ullrich-Turner syndrome)

 miscellaneous

• cleft lip/cleft palate
• meningomyelocele
• hemivertebrae

Case records

 Case 10143

References

 Holder AM, Klaassens M, Tibboel D, de Klein A, Lee B, Scott DA. Genetic factors in congenital diaphragmatic hernia. Am J Hum Genet. 2007 May;80(5):825-45. PMID: 17436238

 Slavotinek AM. The genetics of congenital diaphragmatic hernia.Semin Perinatol. 2005 Apr;29(2):77-85. PMID: 16050525

 Wilcox DT, Irish MS, Holm BA, Glick PL. Pulmonary parenchymal abnormalities in congenital diaphragmatic hernia. Clin Perinatol. 1996 Dec;23(4):771-9. PMID: 8982570