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Fryns syndrome


Monday 17 May 2004

Fryns syndrome (FS) is the commonest autosomal recessive syndrome associated with congenital diaphragmatic hernia (CDH) and comprises CDH, pulmonary hypoplasia, craniofacial anomalies, distal limb hypoplasia, and internal malformations.

Majority are stillborn or die in early neonatal period. 14% of patients survive with polyhydramnios. Autosomal recessive inheritance.

Synopsis (MIM.229850)

- Large for gestational age

- craniofacial anomalies

  • coarse facies
  • microretrognathia
  • abnormal helices
  • cloudy cornea
  • microphthalmia
  • broad nasal bridge
  • anteverted nares
  • macrostomia
  • orofacial clefting (cleft lip, cleft palate)
  • short broad neck

- cardiovascular anomalies

- pulmonary anomalies

  • pulmonary lobation defect
  • pulmonary hypoplasia

- thoracic anomalies

  • small thorax
  • chylothorax
  • broad medial ends of clavicle

- congenital diaphragmatic hernia (often unilateral)

- abdominal anomalies

- male reproductive system

- female reproductive system

  • bicornuate uterus
  • uterine atresia
  • cervical atresia

- renal anomalies

- Hands

  • brachytelephalangy (acral hypoplasia or distal digital hypoplasia or short terminal phalanges)
  • prominent fingertip pads
  • camptodactyly
  • thumb anomalies (proximal thumbs)
  • single transverse palmar crease

- distal limb hypoplasia
- broad clavicles

- Skin

  • prominent fingertip pads
  • single transverse palmar crease
  • hypoplastic nails, nail hypoplasia
  • nail agenesis (absent nails)

- Central nervous system

  • mental retardation in survivors
  • Dandy-Walker malformation (11807905)
  • agenesis of the corpus callosum
  • arrhinencephaly
  • hypoplasia of the optic tract
  • hypoplasia of olfactory tract
  • ventricular dilatation or hydrocephalus
  • agenesis of the corpus callosum
  • neuronal or cerebellar heterotopias

- polyhydramnios


- Fryns syndrome in monozygotic twins (17384863)


- mosaicism for a tandem duplication of 1q24-q31.2
- anomalies of chromosome 15 (ring chromosome 15)
- 15q26.2 microdeletions (16141010)
- 8p23.1 microdeletions (16141010)
- anomalies of chromosome 6 (terminal deletion of 6q)
- anomalies of chromosome 22
- aneuploidy


- Slavotinek AM. Fryns syndrome: a review of the phenotype and diagnostic guidelines. Am J Med Genet. 2004 Feb 1;124A(4):427-33. PMID: 14735597

- Witters I, Devriendt K, Spinnewijn D, Moerman P, Van Assche FA, Fryns JP. MCA syndrome with renal-hepatic-pancreatic dysplasia, posterior fossa cyst, symmetrical limb deficiencies, cleft palate, cardiac and Mullerian duct anomalies. Am J Med Genet. 2002 Jan 22;107(3):233-6. PMID: 11807905

- Pierson DM, Subtil A, Taboada E, Butler MG. Newborn with anophthalmia and features of Fryns syndrome. Pediatr Dev Pathol. 2002 Nov-Dec;5(6):592-6. PMID: 12375132

- Ayme S, Julian C, Gambarelli D, Mariotti B, Luciani A, Sudan N, Maurin N, Philip N, Serville F, Carles D, et al. Fryns syndrome: report on 8 new cases. Clin Genet. 1989 Mar;35(3):191-201. PMID: 2650934