Journal of Postgraduate Medicine
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Year : 2002  |  Volume : 48  |  Issue : 2  |  Page : 129-30  

Fryns syndrome.

SM Jog, SK Patole, JS Whitehall 
 Department of Neonatology, Kirwan Hospital for Women, Townsville, Queensland 4814, Australia., Australia

Correspondence Address:
S M Jog
Department of Neonatology, Kirwan Hospital for Women, Townsville, Queensland 4814, Australia.

How to cite this article:
Jog S M, Patole S K, Whitehall J S. Fryns syndrome. J Postgrad Med 2002;48:129-30

How to cite this URL:
Jog S M, Patole S K, Whitehall J S. Fryns syndrome. J Postgrad Med [serial online] 2002 [cited 2023 Jun 6 ];48:129-30
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A 17-year-old (G1P0) Australian aboriginal mother delivered a male neonate weighing 2400 grams following a spontaneous vaginal delivery at term. Antenatal scan at 29 weeks’ gestation had shown congenital diaphragmatic hernia (CDH) along with multiple anomalies suggestive of Fryns syndrome [Figure:1,2]. There was no polyhydramnios. Karyotyping was normal and alpha-foetoprotein was in normal range. The neonate was electively intubated in view of CDH (Apgar scores: 3 and 5 at 1 and 5 minutes respectively). Clinical examination revealed multiple congenital anomalies associated with right-sided CDH suggestive of Fryns syndrome. They included coarse facial features, hypertelorism, corneal clouding, broad nasal root, absent malformed right ear, rudimentary left ear with absent external auditory canal, very short neck, and a scaphoid abdomen due to the large CDH with herniation of liver in the thoracic cavity. The limb abnormalities included absent right radius, clinodactly, hypoplasia of the thumb, and long slender fingers, simian crease on right hand, and increased space between first and second toes. There were 11 ribs bilaterally and hemivertebrae were noted at C6 and T1 level. Echocardiography revealed large ventricular septal defect, atrial septal defect and left pulmonary artery could not be visualised. Head ultrasound revealed dilated lateral ventricles whereas renal scan was normal. Death occurred at 18 hours of age after withdrawal of life support following failure of maximal medical therapy for pulmonary hypoplasia with severe persistent pulmonary hypertension of the newborn. Withdrawal of life support was delayed mainly to allow appropriate counselling of the mother. Autopsy was not done as per the wish of the mother. There was no history of similar problems in the family.

  ::   DiscussionTop

Fryns syndrome is an autosomal recessive, multiple congenital anomaly syndrome with an incidence of 1 in 10,000 births.[2] It is characterised by CDH, unusual facies and distal limb hypoplasia. The spectrum of distal limb hypoplasia includes short and broad hands, short digits, short or absent terminal phalanges, hypoplastic or absent nails, and clinodactyly. Though distal digital hypoplasia is universal, to our knowledge radial hypoplasia has not yet been reported in Fryns syndrome. Radial hypoplasia and hypoplasia/aplasia of the thumb are commonly seen together in Roberts- SC phocomelia, Vater association, and in Holt-Oram, Levy-Hollister, Baller-Gerold, Fanconi pancytopenia, radial aplasia-thrombocytopenia, and Aase syndromes. However, these are not associated with CDH. They are also seen together (without CDH) occasionally in Cat eye, de Lange, Seckel syndromes, trisomy 13, 18, and foetal valproate syndromes.

The Pallister-Killian Syndrome, one of the close differentials of Fryns syndrome, is a rare polymalformative complex characterised by a tissue specific mosaic distribution of an additional isochromosome 12p and characterised by CDH, rhizomelic limb shortening, facial anomalies and, rarely, acral hypoplasia.[1] Chromosomes of peripheral lymphocyte are usually normal in Pallister-Killian syndrome, but tissue cultures show varying degrees of mosaicism for isochromosome 12p. Since CDH and acral hypoplasia can also be found in Fryns syndrome, the differential diagnosis between the two conditions depends on the demonstration of the 12p isochromosome by FISH test on fibroblast/bone marrow cultures. Such an approach avoids inappropriate counselling by giving an erroneously high recurrence risk in any newborn with CDH and dysmorphic features and a normal peripheral blood karyotype.

Neurologic and cardiac malformations have been reported in up to 72% and 88% of Fryns syndrome cases respectively. First described in 1979, this syndrome is usually associated with stillbirth and death soon after birth.[2] Patients who survive the neonatal period represent 14% of reported cases.[3] Characteristics of survivors include less frequent CDH and milder lung hypoplasia, absence of complex cardiac malformations, frequent early myoclonus, and most often, severe neurologic impairment.[3],[4] A significant inter and intra-familial phenotypic variability as well as discordant phenotype in monozygotic twins has been reported.[5],[6] Detection of foetal hydrops, cystic hygroma, and multiple pterygia have allowed prenatal ultrasonographic diagnosis as early as in the 11th week of gestation.[6]


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2Pinar H, Carpenter MW, Abuelo D, Singer DB. Fryns syndrome: a new definition. Pediatr Pathol 1994;14:467-78.
3Van Hove JL, Spiridigliozzi GA, Heinz R, McConkie-Rosell A, Iafoll AK, Kahler SG. Frynssyndrome survivors and neurologic outcome. Am J Med Genet 1995;59:334-40.
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5Ramsing M, Gillessen–Kaesbach G, Holzgreve W, Fritz B, Rehder H. Variability in the phenotypic expression of Fryns syndrome: report of two sibships. Am J Med Genet 2000;95:415-24.
6Vargas JE, Cox GF, Korf BR. Discordant phenotype in monozygotic twins with Fryns syndrome. Am J Med Genet 2000;94:42-5.

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