Congenital diaphragmatic defects and associated syndromes, malformations, and chromosome anomalies: A retrospective study of 60 patients and literature review

Abstract

Congenital diaphragmatic defects (CDDs) may occur in malformation syndromes of varied causes. Syndromic cases of CDDs due to chromosomal defects, autosomal recessive, autosomal dominant, or X-linked inheritance have been described. In order to determine the frequency and nature of syndromes, malformations, and chromosome abnormalities associated with CDDs, we reviewed the records of all patients with CDDs evaluated over a 4-year period. During the 4-year interval, a total of 60 patients was evaluated. Of these, 29 had a therapeutic or spontaneous abortion, and 31 received postnatal care. On prenatal ultrasonography, 20 of 60 (33%) of patients with CDDs had additional anomalies. Additional anomalies, besides CDDs, were present in 15 of 31 (48%) of liveborn patients on newborn evaluation. In total, 16 patients with multiple anomalies were evaluated. Of these, 12 of 16 (75%) had additional abnormalities detected by prenatal ultrasonography. The 4 of 16 (25%) without additional anomalies on prenatal sonography had multiple anomalies found neonatally, lethal multiple pterygium syndrome being diagnosed in one case. Prenatal chromosome analysis was performed in 7 of 16 patients, and all had postnatal karyotypes. All initial karyotypes were normal. Tetrasomy 12p was documented on postnatal fibroblast analysis in one case who had percutaneous umbilical blood sampling (PUBS). Syndromes diagnosed postnatally in 7 of 16 patients (44%) include: Fryns syndrome (2), Simpson-Golabi-Behmel syndrome (2), tetrasomy 12p (1), Brachmann-de Lange syndrome (1), and lethal multiple pterygium syndrome (1). We were unable to make a specific diagnosis in 9 of 16 patients (56%) with multiple malformations. In patients with CDDs, a normal prenatal karyotype, especially if obtained by PUBS, and absence of other detected abnormalities by fetal ultrasonography, do not exclude the presence of other major anomalies, including chromosome abnormalities and severe multiple malformation syndromes.

Infants with Bochdalek diaphragmatic hernia: Sibling precurrence and monozygotic twin discordance in a hospital‐based malformation surveillance program

“…Two studies have shown that the rate of occurrence in siblings is low, in the order of 1% [David and Illingworth, 1976;Czeizel and Kovacs, 1985]. However, several observations indicate that CDH can be due to genetic abnormalities, including: (a) reports of an appreciable number families with multiple affected relatives diagnosed with CDH [Wolff, 1980;Norio et al, 1984]; (b) the identification of de novo mutations in important developmental genes in patients with CDH [Devriendt et al, 1995;Denamur et al, 2000;Reardon et al, 2004;Ackerman et al, 2005]; and (c) the many human single gene disorders and chromosome abnormalities that occur in association with CDH [Enns et al, 1998;Lurie, 2003]. …”

Congenital diaphragmatic hernia in a patient with tetrasomy 9p

“…CDH is a malformation with an estimated prevalence of 1/2000 to 1/3000 [6], with 84% being left-sided, 13% rightside, and 2% bilateral [3]. CDH may occur as an isolated malformation or in multiple malformation syndromes and associations.…”

“…Several authors have shown that midline anomalies are commonly associated with CDH [10 -12]. Several malformation syndromes, including Fryns syndrome, Beckwith-Wiedemann syndrome, SimpsonGolab-Behmel syndrome, Donnai syndrome, and Perlmann syndrome, associated with CDH also have midline defects as components of their phenotype [3].…”

“…Congenital diaphragmatic hernia (CDH) may occur as an isolated event, as part of a malformation syndrome, or associated with chromosomal defects [3]. CDH is most frequently documented with trisomy 18, 13, and 21 [4], although an association between CDH and chromosome 15q defects has also been documented [3,5].…”

“…CDH is most frequently documented with trisomy 18, 13, and 21 [4], although an association between CDH and chromosome 15q defects has also been documented [3,5]. Regarding chromosome 9 anomalies associated with CDH, there are some anecdotal papers reporting deletions and translocations [5][6][7], but no case of tetrasomy has been reported.…”