Fryns syndrome is characterized by diaphragmatic defects (diaphragmatic hernia, eventration, hypoplasia, or agenesis); characteristic facial appearance (coarse facies, wide-set eyes, a wide and depressed nasal bridge with a broad nasal tip, long philtrum, low-set and anomalous ears, tented vermilion of the upper lip, wide mouth, and a small jaw); short distal phalanges of the fingers and toes (the nails may also be small); pulmonary hypoplasia; and associated anomalies (polyhydramnios, cloudy corneas and/or microphthalmia, orofacial clefting, renal dysplasia / renal cortical cysts, and/or malformations involving the brain, cardiovascular system, gastrointestinal system, and/or genitalia). Survival beyond the neonatal period is rare. Data on postnatal growth and psychomotor development are limited; however, severe developmental delay and intellectual disability are common.

WT1 disorder is characterized by congenital/infantile or childhood onset of steroid-resistant nephrotic syndrome (SRNS), a progressive glomerulopathy that does not respond to standard steroid therapy. Additional common findings can include disorders of testicular development (with or without abnormalities of the external genitalia and/or müllerian structures) and Wilms tumor. Less common findings are congenital anomalies of the kidney and urinary tract (CAKUT) and gonadoblastoma. While various combinations of renal and other findings associated with a WT1 pathogenic variant were designated as certain syndromes in the past, those designations are now recognized to be part of a phenotypic continuum and are no longer clinically helpful.

A rare, syndromic diabetes mellitus characterized by partial pancreatic agenesis, diabetes mellitus, and heart anomalies (including transposition of the great vessels, ventricular or atrial septal defects, pulmonary stenosis, or patent ductus arteriosis).

SRXX5 is characterized by genital virilization in 46,XX individuals, associated with congenital heart disease and variable somatic anomalies including blepharophimosis-ptosis-epicanthus inversus syndrome (BPES) and congenital diaphragmatic hernia (Bashamboo et al., 2018).

Diaphragmatic hernia-4 with cardiovascular defects (DIH4) is an autosomal recessive congenital anomaly syndrome characterized by the presence of diaphragmatic hernia or eventration apparent at birth. Affected infants have associated pulmonary hypoplasia and respiratory insufficiency resulting in death in infancy. Most also have variable cardiovascular defects, including aortopulmonary window or conotruncal anomalies. Dysmorphic facial features and mild distal limb anomalies are sometimes observed (Beecroft et al., 2021). For a discussion of genetic heterogeneity of congenital diaphragmatic hernia (CDH), see DIH1 (142340).