Table 3.

Genes of Interest in the Differential Diagnosis of MYRF-Related Cardiac Urogenital Syndrome

Gene(s)DisorderMOIKey FeaturesDistinguishing Features / Comment
FAM111A Kenny-Caffey syndrome type 2 (KCS2) (See FAM111A-Related Skeletal Dysplasias.)ADNanophthalmos, short stature, hypocalcemia, thickening medullary & cortical boneKCS2 is assoc w/macrocephaly & low birth weight. 1
GATA4 Testicular anomalies ± congenital heart disease (TACHD) (OMIM 615542)ADCHD, GU anomalies incl ambiguous genitaliaCDH, ocular, & pulmonary anomalies are not reported in TACHD. 2
MFRP MFRP-related nanophthalmos (OMIM 609549)ARNanophthalmos, retinal degenerationSyndromic features are not reported in MFRP-related nanophthalmos. 3
NR2F2 46,XX sex reversal (SRXX5) (OMIM 618901)AD46,XX ambiguous genitalia or sex reversal, müllerian anomalies, HLHS, CDH (1 person)SRXX5 is assoc w/ambiguous (nonbinary) genitalia in 46,XX persons (vs 46,XY persons in CUGS) & eyelid anomalies; hyperopia is not reported. 4
PIGL PIGL-related disorder 5ARCDH, ambiguous genitalia (1 family)PIGL-related disorder is assoc w/coloboma, vermian hypoplasia, & cleft palate. 5
PRSS56 PRSS56-related nanophthalmos 6ARNanophthalmos, posterior microphthalmosSyndromic features are not reported in PRDD56-related nanophthalmos. 6
RLIM Tonne-Kalscheuer syndrome (TOKAS) (OMIM 300978)XLDD, microcephaly, CHD, CDH, GU anomalies (cryptorchidism, hypospadias, micropenis)TOKAS is assoc w/hypertelorism, a long, narrow face, & micrognathia. 7
SPECC1L Teebi hypertelorism syndrome 1 (TBHS1) (OMIM 145420)ADHypertelorism, CDH, CHD, müllerian anomaliesIn TBHS1, CDH is rare, pulmonary hypoplasia is only reported as secondary to CDH or omphalocele, hypertelorism is a prominent feature, & CHD are limited to ASD/VSD. 8
TMEM98 TMEM98-related nanophthalmos (OMIM 615972)ADNanophthalmosSyndromic features have not been reported in TMEM98-related nanophthalmos. 9
WT1 Meacham syndrome (See WT1 Disorder.)ADCDH, pulmonary dysplasia, complex CHD, & GU abnormalities incl ambiguous genitalia & gonadal dysgenesisA person w/clinical diagnosis of Meacham syndrome was later found to have MYRF-CUGS. 10

AD = autosomal dominant; AR = autosomal recessive; ASD = atrial septal defect; CDH = congenital diaphragmatic hernia; CHD = congenital heart defects; GU = genitourinary; HLHS = hypoplastic left heart syndrome; MYRF-CUGS = MYRF-related cardiac urogenital syndrome; MOI = mode of inheritance; VSD = ventricular septal defect; XL = X-linked

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From: MYRF-Related Cardiac Urogenital Syndrome

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