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2018-07-15  Case of the week # 476  © Ahmed Ezz

Answer to the case of the week # 476
August 2, 2018 - August 16, 2018

Fellow at El Kaser El Eany Fetal Medicine Unit – Cairo university 


Case report

A young woman (G3P2) was referred  to our unit for anomaly scan due to polyhydramnios at 26 weeks of gestational age. 

Her history was unremarkable and her first trimester ultrasound was normal.


Our ultrasound examination revealed the following findings:

  • Polyhydramnios , AFI = 30 cm
  • Left sided diaphragmatic hernia with displacement of the heart  toward the right
  • Agenesis of  the  corpus callosum (absent cavum septum pellucidum (CSP) and dilated lateral ventricle = 13 mm with teardrop sign ) 
  • Prefrontal oedema 
  • Increased nuchal  fold 
  • Facial dysmorphism:
    • Coarse features
    • Hypertelorism
    • Broad nasal bridge & long philtrum
    • Low-set ears
    • Macrostomia, micrognathia( mild) 
  • Distal digital nail hypoplasia,
  • Both kidneys are enlarged, Homogenous with 
  • Small peripheral cortical cysts 

An amniocentesis was done and the result was normal karyotype ( 46 XX).

Based on ultrasound findings, our diagnosis  was Fryns syndrome and it was confirmed by postnatal genetic evaluation.




Images 1-4, video 1 and 2: 2D images showing hypertelorism, abnormal fetal profile, increased nuchal fold and ventriculomegaly, and indirect sign of agenesis of the corpus callosum.



Images 5-8, video 3:
2D images showing left diaphragmatic hernia, and enlarged kidneys with cortical microcysts.



Images 9-14, video 4: 3D images of the fetal face and limbs, showing mild micrognathia and digital hypoplasia.




Fryns syndrome is characterized by diaphragmatic defects (diaphragmatic hernia), facial dysmorphism (hypertelorism, broad/flat nasal bridge, long philtrum, low-set ears, tented upper lip, macrostomia, micrognathia), distal digital nail hypoplasia, and pulmonary hypoplasia. Other anomalies include ocular findings (cloudy corneas, microphthalmia), orofacial clefting, and renal dysplasia.

Incidence is estimated at 7 per 100,000 live births in France, and 1% to 10% of patients with CDH.
No specific gene has been implicated. Inheritance is autosomal recessive.
Recurrence risk
Recurrence risk is 25%.
Frequent ultrasound findings
- Congenital diaphragmatic hernia (90%)
- Pulmonary hypoplasia (65%)
- Dysmorphic facial features
  * Hypertelorism
  * Mid face hypoplasia
  * Low-set /malformed ears
  * Micrognathia
  * Macrostomia
-  Distal limb hypoplasia
  * Rudimentary development  of the distal phalanges
-Congenial heart  defects (50%)

Uncommon ultrasound findings
- Ventriculomegaly (23%)
- Agenesis of  the  corpus callosum (13.5%)
- Dandy-Walker malformation 
- Cystic hygroma
- Cleft lip and palate
Diagnosis is based on the clinical findings. The phenotypic variability makes sonographic diagnosis a challenge. Prenatally, CDH and facial dysmorphism may be seen. Development of polyhydramnios late in the second trimester and normal growth or overgrowth of the fetus are also expected.
Differential diagnosis
The differential diagnosis includes chromosomal disorders, Pallister-Killian syndrome (mosaic tetrasomy 12p), Donnai-Barrow syndrome, Zellweger syndrome.
The majority of affected infants are stillborn or die in early neonatal period. Severe intellectual and developmental delay is often reported in those who survive.

Ayme S, Julian C, Gambarelli D, et al: Fryns syndrome: report on 8 new cases. Clin Genet 35(3):191–201, 1989.
Barthe B, Cohen H, Saada P: [Prenatal diagnosis of a case of Fryns’syndrome]. J Gynecol Obstet Biol Reprod 24(1):57–62, 1995.
Fryns JP: Prenatal diagnosis and long survival of Fryns syndrome. Prenat Diagn 15(1):97–98, 1995.
Gadow EC, Lippold S, Serafin E, et al: Prenatal diagnosis and long survival of Fryns’ syndrome. Prenat Diagn 14(8):673–676, 1994.
Ramsing M, Gillessen-Kaesbach G, Holzgreve W, et al: Variability in the phenotypic expression of Fryns syndrome: a report of two sibships. Am J Med Genet 95(5):415–424, 2000.
Slavotinek A: Fryns syndrome. In Pagon RA, Adam MP, Ardinger HH, et al, editors: GeneReviews, Seattle, 1993–2016, University of Washington.

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