Developmental and cytological phenotypes of cohesinopathies and potentially related maladies.

Partial list of developmental and cytological effects in response to cohesion pathway mutations.*Craniofacial dysmorphia include micrognathia, ear abnormalities, wide-set eyes, beaked or prominent nose, arched eyebrows, or low-set ears.+Limb reductions are often symmetric and involve all four limbs in RBS but predominant in upper extremities in CdLS. Limb reduction appears limited to the radius in NBS and FA.**Organ abnormalities may include renal, urinary, gonadal, gastroesophageal, and others.++Detection of cryptic HR/PCS may require cell exposure to mitomycin. ND (Not Diagnostic): most studies document that HR/PCS is not elevated in CdLS cells [17], [18], [20], but see [48]. While HR/PCS is thus not efficacious as a diagnostic tool, numerous chromosomal aberrations are evident in CdLS cells upon exposure to genotoxic agents [20], revealing that CdLS cells may be predispositioned to PCS/HR. Bolded text represents examples of historical cytological diagnostic markers (HR/PCS for RBS, Clastogen sensitivity for FA). Phenotypes shown for potentially cohesinopathic-related developmental maladies (Ribosomopathies TCS and DBA, Nijmegen Breakage Disease, Fanconi Anemia—last four columns) that we speculate are similarly predicated on transcriptional dysregulation [1], [2], [5]–[8], [14], [26], [33], [41], [48], [55]–[57], [61], [63], [78], [79].