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

• ventricular septal defect
• atrial septal defect
• aortic arch 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

• ectopic pancreatic tissue
• multiple accessory spleens
• intestinal malrotation
• omphalocele
• esophageal atresia
• Meckel diverticulum
• duodenal atresia
• aganglionosis of colon
• imperforate anus

 male reproductive system

• cryptorchidism
• hypospadias
• bifid scrotum

 female reproductive system

• bicornuate uterus
• uterine atresia
• cervical atresia

 renal anomalies

• hydronephrosis
• dilatation of the ureters
• renal agenesis
• renal cysts
• renal dysplasia

 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
• 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

Cytogenetics

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

References

 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#

 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#