m e d i c a l j o u r n a l a r m e d f o r c e s i n d i a 7 8 ( 2 0 2 2 ) 1 0 9 e1 1 2

Available online at www.sciencedirect.com

ScienceDirect

j o u r n a l h o m e p a g e : w w w . e l s e v i e r . c o m / l o c a t e / m j a fi

Case Report

When Fryn met Edward: Two rare syndromes in a

single patient

Nikunj Nandan a, V. Shankar Raman b,*, Santosh Dey c, Deepak Dwivedi d

a
Resident, Department of Surgery, Armed Forces Medical College, Pune, 411040, India
b
Senior Advisor (Surgery & Pediatric Surgery), Command Hospital (Southern Command), Pune, 411040, India
c
Classified Specialist (Surgery & Pediatric Surgery), Command Hospital (Southern Command), Pune, 411040, India
d
Senior Advisor (Anaesthesia & Pediatric Anaesthesia), Command Hospital (Southern Command), Pune, 411040,
India

article info abstract

Article history: A neonate born at our centre was diagnosed as Fryns Syndrome ie congenital diaphrag-
Received 22 July 2019 matic hernia with facial dysmorphism and distal limb anomalies, which is a rare disorder
Accepted 16 October 2019 with only a few hundred cases reported till date.With high clinical index of suspicion and
Available online 8 January 2020 further evaluation, the diagnosis was confirmed. The baby was initially stabilized and later
underwent repair of the diaphragmatic hernia. Despite best measures, the baby could not
Keywords: be salvaged. When severe, this can be lethal and diagnosis can only be made after autopsy.
Fryns syndrome However, with early suspicion, better modalities of investigations available and improved
Congenital diaphragmatic hernia NICU care, these babies can be salvaged. We report a case of Fryns Syndrome who was
Edward syndrome incidentally found to have Edward Syndrome as well. Such an extremely rare combination
Genetic counseling is yet to be reported in medical literature.Also with updated genetic studies, better di-
agnostics and treatment options coming up in future, there are chances to improve the
survivability of these babies. It is prudent to document all such cases to aid in better un-
derstanding of the disease process.
© 2020 Director General, Armed Forces Medical Services. Published by Elsevier, a division of
RELX India Pvt. Ltd. All rights reserved.

2. Distinct craniofacial anomalies including coarse face, flat

Introduction
Fryns syndrome is a rare disorder with only a few hundred
cases described so far.1 Initially reported by Fryns et al., in
1979, the diagnostic guidelines were laid down by Fryns in
1987, which included a combination of these major features:2
1. Hydramnios in the 2nd trimester of pregnancy with normal
fetal growth
nasal bridge, poorly shaped auricles, etc.
3. Narrow thorax, hypoplastic and widely placed nipples
4. Distal limb hypoplasias or absent nails
5. Internal malformations including diaphragmatic defects
with lung hypoplasia, cerebral malformations, and mal-
formations in the GI and genitourinary tract
6. External malformations including cloudy cornea, micro-
phthalmia, and short neck with nuchal folds.

* Corresponding author.
E-mail address: shankyafmc@yahoo.com (V.S. Raman).
https://doi.org/10.1016/j.mjafi.2019.10.005
0377-1237/© 2020 Director General, Armed Forces Medical Services. Published by Elsevier, a division of RELX India Pvt. Ltd. All rights
reserved.
110 m e d i c a l j o u r n a l a r m e d f o r c e s i n d i a 7 8 ( 2 0 2 2 ) 1 0 9 e1 1 2

A narrow definition of Fryns syndrome says 4 of the above 6

features to be present, although a broad criterion suggests
that 3 of 6 is sufficient.3 Several other authors have made
modifications in these criteria as per their observations of
various cranial and cardiovascular malformations. This index
case had 5 of 6 features as per the criteria afforementioned.
There have also been cases of Fryns syndrome without
congenital diaphragmatic hernia (CDH), which was earlier
considered to be a cardinal feature.4
In this case report, we present a combination of two rare
disorders seen together, that is, Fryns syndrome along with
Edwards syndrome. To the best of our knowledge, such a
combination has not been documented till date.

Case report

A newborn low birth weight (1.91 kg) male baby was born by
lower segment caesarian section to a high risk multigravida
mother with a known history of gestational diabetes mellitus,
polyhydramnios and antenatally diagnosed truncus arterio-
sus. The baby was intubated at birth in view of cyanosis,
respiratory distress, and poor respiratory effort.
On head to toe examination, the baby was found to have
dysmorphic features including microphthalmia, anti-
mongoloid slant, hypertelorism, small malformed low-lying
ears, small mouth (Fig. 1), polydactyly (Fig. 2) and posteriorly
placed anal orifice. Respiratory examination revealed suspi-
cion of bowel sounds over left hemithorax although chest
auscultation was suggestive of systolic murmur with shifting
of apex beat towards right side of the chest. The abdomen
looked scaphoid.
The chest radiograph revealed herniation of bowel loops
into left hemithorax (Fig. 3) and the ultrasonography was
suggestive of CDH (left) with mediastinal shift to right, with
displaced bowel loops and spleen in the left hemithorax. 2D
echocardiography revealed truncus arteriosus type A (Van
Fig. 2 e Dysmorphism: Polydactyly right hand.
Braag's), large malaligned subtruncal ventricular septal
defect with ~60% override, dilated left atrium and left
ventricle, severe pulmonary artery hypertension, aortic arch
poorly visualized (grossly left arch with no coarctation of
aorta; tiny patent ductus arteriosus). Subsequent karyotyp-
ing also revealed Edwards syndrome, that is, 47 e XY þ18
(Fig. 4).
The baby was stabilized and underwent repair of CDH (left)
on day 4 of life. Peroperative findings were a large postero-
lateral diaphragmatic defect, herniation of the left lobe of
liver, spleen and stomach, and normal morphology of the left
lung.
The postoperative recovery was gradual but steady. The
child developed progressive respiratory failure and features of
sepsis and inspite of the best intensive care management,
expired on the 14th postoperative day.

Fig. 1 e Dysmorphism: Antimongoloid slant, hypertelorism, microphthalmia with low-set malformed ears and small
mouth.
 m e d i c a l j o u r n a l a r m e d f o r c e s i n d i a 7 8 ( 2 0 2 2 ) 1 0 9 e1 1 2
Fig. 3 e Radiograph suggestive of herniation of bowel loops
into left hemithorax.
Discussion
Fryns syndrome is a rare autosomal recessive disorder with
incidence of about 7 per 1,00,000 live births, affecting both
sexes equally.3 It is among the most common syndromes
associated with CDH with a risk association of
Fig. 4 e Karyotype findings.
111
1e10%,5 includes other features like limb abnormalities and
various dysmorphic features. Various studies are trying to find
out which of these features are a component of the pleiotropic
manifestations of Fryns syndrome and which are a mere
coincidence.1 It should be suspected as soon as a diagnosis of
polyhydramnios with CDH is made in the antenatal or peri-
natal period.
Earlier considered to be a fatal syndrome, the current
standards of care disprove this. With rapid progress in
neonatal care, these babies can now be diagnosed earlier and
necessary intervention can be carried out at the appropriate
time. Depending on severity of signs and symptoms, treat-
ment and prognosis varies from individual to individual. Few
documented cases have been reported to survive till child-
hood requiring continuous supportive care and close follow-
up for developmental delays and intellectual disabilities.4
For diagnosis, clinical evaluation and imaging techniques
suffice. ultrasonography and echocardiography are required to
document other associated anomalies. Magnetic resonance
imaging may be required to assess the lung volumes and
planning extracorporeal membrane oxygenation requirements
and prognosticating overall neonatal survival.7
Specific genes responsible for Fryns are still under study.4 It
is imperative to undergo various chromosomal studies
including karyotyping and chromosomal microarray analysis
before arriving at a conclusive diagnosis of Fryns. Various other
syndromes have been described which have overlapping fea-
tures with Fryns and characteristic features to differentiate
them from the same. Some of which include Pallister-Killian
syndrome, Donnai-Barrow syndrome, Matthew-Wood
syndrome, etc.6
Management depends on treating various abnormalities as
per their priority. A multimodality approach including
112 m e d i c a l j o u r n a l a r m e d f o r c e s i n d i a 7 8 ( 2 0 2 2 ) 1 0 9 e1 1 2
pediatric surgeon, pediatric cardiologist, nephrologist,
gastroenterologist, craniofacial specialist, genetic counselor,
etc. is required to treat the entire spectrum of abnormalities
associated with Fryns.4
There have been no reports of reproduction in patients
with Fryns syndrome till date. However, being an autosomal
recessive disorder, at conception each sibling of an affected
individual has a 25% chance of being affected, 50% chance of
being an asymptomatic carrier and 25% chance of neither
being affected nor being a carrier. In addition, once an at-risk
sibling is unaffected, the risk of him/her being a carrier is 2/3.
Hence, the role of genetic counseling is of paramount impor-
tance in such cases. The optimal time for determination of
genetic risk and prenatal testing is before pregnancy.8 In
future, when better testing methodology and detailed under-
standing of genes is available, such patients can be offered
DNA, that is, deoxyribonucleic acid banking facilities which is
storage of DNA typically extracted from the white blood cells.
Edward syndrome, on the other hand, is a fairly known
chromosomal disorder, and is the second most common tri-
somy after trisomy 21. There is high frequency of fetal loss and
pregnancy termination after prenatal diagnosis. At present,
most of these cases are diagnosed prenatally based on
screening by maternal age, sonographic features and maternal
serum marker screening. Cardiac and renal malformations are
the usual major abnormalities and the most common cause of
death are related to either cardiac failure or respiratory insuf-
ficiency. The severity and complexity of clinical presentation of
these babies with high mortality rate makes the perinatal and
neonatal management very challenging.9
The purpose of this case report is to highlight the features
of Fryns syndrome and mention this rare association with
Edwards syndrome. With detailed genetic studies, higher
imaging modalities and better treatment options coming up in
future, there is always a ray of hope for these babies. In
addition, with very little literature available on Fryns
syndrome, it is prudent to document all such cases so as to aid
in better understanding of the disease.
Conflicts of interest
The authors have none to declare.
references
1. Bacewicz L, Polnik D, Ganowicz J, Anasiewicz AA, Kalicin  ski P.
Fryns syndrome e case report. Documentation of anomalies
not described previously and review of the literature. Pol Przegl
Chir. 2009;81:149e150.
2. Slavotinek AM. Fryns syndrome: a review of the phenotype
and diagnostic guidelines. Am J Med Genet. 2004;124A:427e433.
3. Cunnif C, Jones KL, Saal HM, Stern HJ. Fryns Syndrome: an
autosomal reccesive disorder associated with craniofacial
anomalies, diaphragmatic hernia & distal digital hypoplasia.
Paediatr Am Acad Paediatr. 1990;85:499e504.
4. Vasudevan PC, Stewart H. A case of Fryns syndrome without
diaphragmatic hernia and review of the literature. Clin
Dysmorphol. 2004;13:179e182.
5. Bamforth JS, Leonard CO, Chodirker BN, et al. Congenital
diaphragmatic hernia, coarse facies, and acral hypoplasia:
Fryns syndrome. Am J Med Genet. 1989;32:93e99.
6. Dwivedi T, Hungund B. Fryns syndrome: a rare case report
with review of literature. J NTR Univ Health Sci. 2018;7:147e153.
7. Slavotinek A. Fryns syndrome. In: Adam MP, Ardinger HH,
Pagon RA, et al., eds. Gene Reviews 1993-2019. 2007 Apr 18
[Updated 2015 Jan 29].
8. Slavotinek A, Lee SS, Davis R, et al. Fryns syndrome phenotype
caused by chromosome microdeletions at 15q26.2 and 8p23.1. J
Med Genet. 2005;42:730e736.
9. Cereda A, Carey John C. The trisomy 18 syndrome. Orphanet J
Rare Dis. 2012;7:81.