Table 4.

Genes of Interest in the Differential Diagnosis of Cornelia de Lange Syndrome

GeneDisorderMOIFeatures of Differential Disorder
Overlapping w/CdLSDistinguishing from CdLS
AFF4 CHOPS syndrome (OMIM 616368)ADCognitive impairment, heart defects, short stature, skeletal dysplasiaCoarse facial features, obesity, & pulmonary involvement (features that are not typical for CdLS) 1
ANKRD11 2 KBG syndrome ADDD/ID, short stature, thick eyebrows & synophrys, anteverted nares 3ID is typically milder; macrodontia, few congenital defects
ASXL1 Bohring-Opitz syndrome (BOS)ADDD/ID; prenatal & postnatal growth restriction, microcephaly, hypertrichosis, small feet, facial resemblance w/CdLS (especially infants)Feeding intolerance is usually more severe; high myopia, BOS posture 4, prominent globes
EP300 EP300 Rubinstein-Taybi Syndrome (RSTS)ADDD/ID, small stature, hypertrichosis, full eyebrows, long lashes, micrognathia, malrotation 5Prominent nose & broad thumbs (both less common in EP300-RSTS than in CREBBP-RSTS) 6
TAF1 Intellectual disability syndrome (OMIM 300966)XLDD/ID, long philtrum, anteverted nares, microcephaly, hearing loss 7Generalized hypotonia, long face, protruding ears
TAF6 Alazami-Yuan syndrome (OMIM 617126)ARShort stature, microcephaly, clinodactyly, hirsutism, DD/ID, & facial dysmorphism w/long philtrum, thin & arched eyebrows, synophrys 8Widow’s peak (rare)

AD = autosomal dominant; AR = autosomal recessive; CdLS = Cornelia de Lange syndrome; DD = developmental delay; ID = intellectual disability; MOI = mode of inheritance; XL = X-linked


KBG syndrome is caused by either a heterozygous pathogenic variant in ANKRD11 or deletion of 16q24.3 that includes ANKRD11.


Individuals with Bohring-Opitz syndrome (BOS) can have a specific limb posture termed "BOS posture," described as an external rotation or adduction of the shoulders with flexion of the wrists and fingers at the metacarpophalangeal joint.


EP300 pathogenic variants cause a phenotype that resembles RSTS caused by mutation of CREBBP. However, with the exception of the low-hanging columella, the facial features in EP300-RSTS are less marked. Although the thumbs and halluces are broad, angulation is very uncommon. Intellectual disability is variable but is usually less severe and occasionally normal (see Rubinstein-Taybi Syndrome).


From: Cornelia de Lange Syndrome

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