SPR and Noonan syndrome: Affected siblings in family 00135 each harbored a returnable de novo variant in a different gene, including a VUS in SPR (Dystonia MIM:612716) and a pathogenic variant in RIT1 (Noonan syndrome MIM:615355), while two probands (00075-C and 00078-C) who were second-degree relatives to one another harbored independent pathogenic de novo variants, one each in DDX3X (X-linked ID MIM:300958) and TCF20 (Additional file 2: Table S1).