**3. Classification of CDH**

Congenital diaphragmatic defects (CDD) are classified as posterolateral (Bochdalek, 70-75%) and non-posterolateral according to the location. Nonposterolateral hernias can be retrosternal (Morgagni-Larrey, 23-28%) or central (2-7%), that involves the non-muscular or central tendinous portion of the diaphragm [15]. This anatomical classification has drawbacks as the actual site of lesion may not be easy to discern. Around 85% of the posterolateral CDH are on the left, while 10% are right sided and 5% bilateral. The diaphragmatic eventration is a rare anomaly in which a part or whole of the hemi diaphragm is abnormally elevated into the thoracic cavity, as the normal diaphragmatic musculature is partly or fully replaced by a thin fibro membranous membrane [15], allowing the abdominal viscera to protrude upwards. In order to elucidate the developmental pathways of diaphragmatic defects more accurately, Ackerman et al developed a phenotype worksheet to capture the precise morphological data on CDD by retrospectively analyzing autopsies of 181 cases [16]. They proposed a new classification system

**121**

the parents.

*Congenital Diaphragmatic Hernia: A Major Challenge for Neonatologists*

based on the location and other specifications. According to the fetal imaging CDH can also be classified as intrapleural and mediastinal; this might help in prenatal counselling [17]. Although inadequately studied, the patho-anatomy of the diaphragmatic defects is relevant for understanding the genetics of CDH, as well as for

Sixty percent of the CDH cases are isolated and not associated with any other major malformations. Pulmonary hypoplasia, gut malrotation, cardiac dextro position and left sided heart hypoplasia are considered to be parts of the sequence of CDH and are not regarded as separate entities. The remaining 40% of complex CDH cases are associated with major congenital anomalies in either syndromic or

Environmental factors contributing to CDH are not well investigated. Maternal vitamin A deficiency, nitrofen treatment and retinoid receptor knock-out in animal model are reported to result in CDH in their offsprings, suggesting a role of retinoid signaling pathway in the pathogenesis [18]. Similar effects are seen in WT1 and COUP-TFII mutant mouse models. Beurskens et al found a significantly higher risk of CDH in the infants born to mothers who had low vitamin A intake during pregnancy (Odds ratio, 7.2; 95% confidence interval, 1.5-34.4; p = 0.01)[19]. The cord blood in neonates with CDH is reported to have low retinol and retinol-binding protein levels. Thalidomide and quinine have also been implicated as possible causes

CDH is genetically heterogeneous although can be monogenic. A genetic cause is found in 30% of the cases, even though most cases are sporadic and about 1-2% familial [21]. The application of the next generation sequencing technologies, e.g. DNA array and whole genome sequencing has contributed to the identification of

Chromosomal anomalies account for about 10% of the CDH cases. The common chromosomal aneuploidies associated with CDH are trisomy 18, 13 and 21. Morgagni hernia is more frequently found in trisomy 21 than Bochdalek hernia. Pallister Killian syndrome (PKS), characterized by mosaic tetrasomy 12p is a common chromosomal anomaly associated with CDH and occurs sporadically. The karyotype in PKS is often found to be normal due to a tissue specific distribution of chromosome i12p and reduced yield with culture aging [22, 23]. Establishing diagnosis in such cases depends on the tissue examined and genetic test used [24]. Isochromosome 12p is rarely isolated from cord blood lymphocytes, whereas its yield from the skin fibroblast is close to 100% [25]. Also, the chorionic villus sampling may miss mosaicism, while detection rate of amniocentesis is nearly 90% [23, 26]. Chromosome 12p targeted-FISH, array comparative genomic hybridization (aCGH) or other newer genetic technologies should be used to prevent misdiagnosis in the condition [24, 27]. The availability of information regarding genetic etiology equips the clinicians with better understanding of the prognosis for discussion with

Some of the common monogenic syndromes associated with CDH are Cornelia de Lange, Donnai Barrow and Simpson-Golabi-Behmel, while, others, like Fryn

*DOI: http://dx.doi.org/10.5772/intechopen.94839*

comparing the outcomes.

non-syndromic form.

of CDH [20].

**4.2 Genetics of CDH**

cases with genetic etiology.

**4. Etiopathogenesis of CDH**

**4.1 Environmental factors**

*Congenital Diaphragmatic Hernia: A Major Challenge for Neonatologists DOI: http://dx.doi.org/10.5772/intechopen.94839*

based on the location and other specifications. According to the fetal imaging CDH can also be classified as intrapleural and mediastinal; this might help in prenatal counselling [17]. Although inadequately studied, the patho-anatomy of the diaphragmatic defects is relevant for understanding the genetics of CDH, as well as for comparing the outcomes.

Sixty percent of the CDH cases are isolated and not associated with any other major malformations. Pulmonary hypoplasia, gut malrotation, cardiac dextro position and left sided heart hypoplasia are considered to be parts of the sequence of CDH and are not regarded as separate entities. The remaining 40% of complex CDH cases are associated with major congenital anomalies in either syndromic or non-syndromic form.
