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CASE REPORT
Year : 2013  |  Volume : 2  |  Issue : 2  |  Page : 130-132

Congenital diaphragmatic hernia with hypoplastic lungs, heart, and additional anomalies: A case of ? Fryns syndrome


Department of Pathology, K. L. E. University’s Jawaharlal Nehru Medical College, Belgaum, Karnataka, India

Date of Web Publication21-May-2013

Correspondence Address:
Panduranga Chikkannaiah
Department of Pathology, K. L. E. University’s Jawaharlal Nehru Medical College, Belgaum, Karnataka – 590 010
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/2277-8632.112346

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  Abstract 

Congenital diaphragmatic hernia (CDH) is a common congenital anomaly that frequently occurs in conjunction with other major anomalies, including chromosomal abnormalities. Fryns syndrome (FS) is a lethal syndrome that most frequently features CDH as a cardinal feature in addition to pulmonary hypoplasia, coarse facies, distal digital hypoplasia, and organ malformations. The exact genetic defect has not yet been identified, although it is regarded to follow an autosomal recessive pattern of inheritance. We describe the autopsy findings of a medically terminated 20 weeks fetus with left-sided CDH, hypoplastic left heart, lungs, horse-shoe kidney and other anomalies, confirming to the phenotypic diagnostic guidelines of FS.

Keywords: Congenital diaphragmatic hernia, Fryns syndrome, horseshoe kidney, pulmonary hypoplasia


How to cite this article:
Roy M, Chikkannaiah P, Bali A. Congenital diaphragmatic hernia with hypoplastic lungs, heart, and additional anomalies: A case of ? Fryns syndrome. J NTR Univ Health Sci 2013;2:130-2

How to cite this URL:
Roy M, Chikkannaiah P, Bali A. Congenital diaphragmatic hernia with hypoplastic lungs, heart, and additional anomalies: A case of ? Fryns syndrome. J NTR Univ Health Sci [serial online] 2013 [cited 2019 Jul 22];2:130-2. Available from: http://www.jdrntruhs.org/text.asp?2013/2/2/130/112346


  Introduction Top


Congenital diaphragmatic hernia (CDH) is a common congenital anomaly with a incidence of 1 in approximately 2000 to 3000 births. [1] Despite an exponential rise in early prenatal diagnosis, and advances in perinatal and postnatal care, CDH remains an anomaly associated with substantial morbidity and mortality, frequently ascribed to presence of associated often multiple anomalies in 50% of cases. [2]

Fryns syndrome (FS) is a rare, lethal, autosomal recessive syndrome most commonly associated with CDH. The original description by Fryns et al. in 1979 included abnormal facies, distal digital hypoplasia, diaphragmatic defect with pulmonary hypoplasia, and organ malformations, involving the heart, brain and genitourinary system as the major diagnostic criteria. [3]

We report the autopsy findings of a 20-weeks female fetus with left-sided CDH and associated hypoplastic left heart, lungs with cystic adenomatoid malformation, horseshoe kidney and other anomalies.


  Case Reports Top


A 23-year-old primigravida underwent a routine prenatal ultrasound at 20-weeks gestation which demonstrated left-sided CDH and associated multiple anomalies. There was no evidence of polyhydramnios. The mother did not give any history of viral fever or unsupervised drug intake. Family history was forthcoming of a first degree consanguineous marriage. The couple opted for termination of the pregnancy.

A female fetus weighing 430 grams was delivered and following parental consent was sent to the department of pathology for a detailed post mortem examination. External survey revealed congenital talipes equinovarus (CTEV) of the right foot. No distal digital hypoplasia was evident. The head was normocephalic and no facial dysmorphism was observed. On dissection, a large left posterolateral CDH was identified with herniation of loops of small intestine, part of stomach, spleen and left lobe of liver into the thoracic cavity [Figure 1]a. Hypoplasia of the lungs and left side of the heart were evident [Figure 1]b. Umbilical cord featured single umbilical artery. Urogenital system dissection demonstrated horseshoe kidney [Figure 1]c. Gross inspection of the central nervous system and spinal cord examination did not reveal any anomaly.
Figure 1: (a) Left-sided posterolateral CDH with herniation of loops of small intestine, part of stomach, spleen and left lobe of liver into the thoracic cavity; (b) Hypoplastic left heart; (c) Horseshoe kidney; (d) Cysts lined by simple cuboidal to columnar epithelium in congenital cystic adenomatoid malformation of lungs

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Microscopic examination of the umbilical cord confirmed presence of a single umbilical artery. Lungs microscopy revealed multiple randomly distributed cysts lined by simple cuboidal to columnar epithelium diagnostic of congenital cystic adenomatoid malformation and compromised normal pulmonary parenchymal growth [Figure 1]d. Microscopic evaluation of other organs was unremarkable.

The conglomeration of left-sided CDH, hypoplastic lungs, heart, renal anomalies and right foot CTEV prompted us to consider a phenotypic diagnosis of Fryns syndrome (FS), a possibility further fuelled by the positive history of consanguinity. Cytogenetic studies were not done.


  Discussion Top


CDH results from defect, or rarely agenesis, of the diaphragm consequent to disruption of the fusion of the diaphragmatic anlagen, namely pleuroperitoneal membrane, septum transversum, dorsal esophageal mesentery, and body wall mesoderm. [4]

CDH occurs more often on the left hemithorax and the commonest subtype is the posterolateral or Bochdalek type. The anterior or Morgagni type is less common and the central type is the rarest. [2],[5]

Additional major anomalies are encountered in 40-50% of cases, notably in the cardiovascular, skeletal, neural, genitourinary, and gastrointestinal system. [1] CDH is a recognized feature in Fryns, Ghersoni-Baruch, WAGR, Denys-Drash, Cornelia de Lange syndrome, as well as various chromosomal abnormalities (trisomy 13, 18, 21, Turner syndrome, Pallister-Killian syndrome). [1]

FS is an autosomal recessive syndrome with a reported incidence of 1 in 10,000 births. It is the commonest syndrome featuring CDH as a cardinal feature with an estimated 10% of patients with CDH having FS. [3] The exact genetic etiology is yet to be established. However, occasional case reports, by de Jong et al., [6] Clarke and Gonzales, [7] Krassikoff and Sekhon, [8] and Slavotinek et al., [3] mention phenotypes similar to FS associated with anomalies of ring chromosome 15, mosaic tandem duplication of chromosome 1q24-31.2, terminal deletion of 6q, microdeletions at 15q26.2 and 8p23.1, respectively.

Diagnostic guidelines for FS has undergone reformulation and currently encompasses six criteria, namely diaphragmatic hernia, pulmonary hypoplasia, craniofacial dysmorphism (coarse facies, ocular hypertelorism, broad and flat nasal bridge, thick nasal tip, long philtrum, low-set and poorly formed ears, tented upper lip, macrostomia, micrognathia), brachytelephalangy with nail hypoplasia, associated anomalies (polyhydramnios, cloudy corneas and/or microphthalmia, orofacial clefting, renal dysplasia/renal cortical cysts, and/or malformation involving brain, cardiovascular, and gastrointestinal system), and affected siblings (or parental consanguinity) suggesting autosomal recessive inheritance. [9] The six proposed criteria are not obligatory and a phenotypic diagnosis of FS typically requires presence of three of the six features (without facies characteristic of another syndrome). [9] Controversies, however, exist regarding the diagnostic criteria. For example, Alessandri et al., described a newborn with features of FS except the CDH. [10]

Several different chromosomal aberrations share phenotypic resemblance to FS, most notably Pallister-Killian syndrome (tetrasomy 12p mosaicism) characterized by CDH, rhizomelic limb shortening, coarse facial features, aortic stenosis, cardiac septal defects, and abnormal genitalia. Cytogenetic analysis is recommended to exclude the different chromosomal disorders prior to making a diagnosis of FS. [3]

Autopsy in our case demonstrated a large left-sided CDH, hypoplastic left heart, lungs, horseshoe kidney, and right foot CTEV conforming to the phenotypic diagnostic guidelines of FS. However, parental refusal to consent for a cytogenetic analysis prevented exclusion of other chromosomal anomalies with phenotypic similarity to FS.

 
  References Top

1.Smith NP, Jesudason EC, Featherstone NC, Corbett HJ, Losty PD. Recent advances in congenital diaphragmatic hernia. Arch Dis Child 2005:90:426-8.  Back to cited text no. 1
    
2.Halamek LP, El-Sayed YY. Congenital diaphragmatic hernia: The perinatalogist's perspective. Pediatr Rev 1999;20:e67-70.  Back to cited text no. 2
    
3.Slavotinek A, Lee SS, Davis R, Shrit A, Leppig KA, Rhim J, et al. Fryns syndrome phenotype caused by chromosome microdeletions at 15q26.2 and 8p23.1. J Med Genet 2005;42:730-6.  Back to cited text no. 3
    
4.Karadeniz L, Guven S, Atay E, Ovali F, Celayir A. Bilateral diaphragmatic defect and associated multiple anomalies. J Chin Med Assoc 2009;72:163-5.  Back to cited text no. 4
    
5.You LR, Takamoto N, Yu CT, Tanaka T, Kodama T, Demayo FJ, et al. Mouse lacking COUP-TFII as an animal model of Bochdalek-type congenital diaphragmatic hernia. Proc Natl Acad Sci USA 2005;102:16351-6.  Back to cited text no. 5
    
6.de Jong G, Rossouw RA, Retief AE. Ring chromosome 15 in a patient with features of Fryns' syndrome. J Med Genet 1989;26:469-70.  Back to cited text no. 6
    
7.Clark RD, Fenner-Gonzales M. Apparent Fryns syndrome in a boy with a tandem duplication of 1q24-31.2. Am J Med Genet 1989;34:422-6.  Back to cited text no. 7
    
8.Krassikoff N, Sekhon GS. Terminal deletion of 6q and Fryns syndrome: A microdeletion/syndrome pair? Am J Med Genet 1990;36:363-4.  Back to cited text no. 8
    
9.Lin AE, Pober BR, Mullen MP, Slavotinek AM. Cardiovascular malformations in Fryns syndrome: Is there a pathogenic role for neural crest cells? Am J Med Genet A 2005;139:186-93.  Back to cited text no. 9
    
10.Alessandri L, Brayer C, Attali T, Samperiz S, Tiran-Rajaofera I, Ramful D, et al. Fryns syndrome without diaphragmatic hernia. Report on a new case and review of the literature. Genet Couns 2005;16:363-70.  Back to cited text no. 10
    


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