The X-linked inheritance, intellectual disability, and asthenic habitus of CK syndrome overlap with several disorders. Recognizing that the physical features of CK syndrome could overlap with non-X-linked disorders, evidence of X-linked inheritance is a critical diagnostic criterion. For completeness, however, other non-X-linked disorders that share similar phenotypes are included here in the differential diagnosis.

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

17p13.3 microduplications are grouped into two classes determined by the presence or absence of three genes: YWHAE, PAFAH1B1, and CRK [Bruno et al 2010]. Class I microduplications (presence of YWHAE but not PAFAH1B1) are associated with autistic features, speech and motor delays, and subtle dysmorphic features. Class II microduplications (presence of PAFAH1B1 and sometimes CRK and YWHAE) are associated with intellectual disability and hypotonia and similar dysmorphic features to the class I microduplication.

Microcephaly is characteristic of individuals with duplication of PAFAH1B1 but not of YWHAE or CRK.

Thevenon et al [2014] reported on seven individuals with chromosome 3q27.3 microdeletions; five individuals had clinical information available. Two small regions of overlap, SRO1 and SRO2, were common to all five individuals and were systematically associated with facial dysmorphism and neurobehavioral problems. Five deleted genes in the SRO1 area (MASP1, ADIPOQ, ST6GAL1, SST, and BCL6) were of interest, SST likely being responsible for psychiatric disorders and ADIPOQ possibly associated with the thin habitus. Seven genes were contained in the SRO2 area: FETU8, KNG1, HRG, DGKG, TBCCD1, AHSG, and CRYGS. AHSG was thought to be a good candidate for the skeletal phenotype and/or the intellectual disability.