IllnessMenke-Hennekam syndrome 1; Rubinstein-Taybi syndrome 1

NGS +

Rubinstein-Taybi Syndrome is a disease characterized by short stature, moderate to severe mental retardation, distinct facial features and broad thumbs/toes. Other variable characteristics include eye, heart and kidney malformations, dental problems and obesity. These patients also have an increased risk of developing benign skin and brain tumors. In addition to causing Rubinstein-Taybi syndrome, pathogenic germline variants of the CREBBP and EP300 genes are also associated with Menke-Hennekam syndrome by missense mutations in exon 30 or 31 of CREBBP or the homologous regions of the EP300 gene, respectively. However, individuals with Menke-Hennekam syndrome do not have typical facial features or broad/angled thumbs. Rubinstein-Taybi syndrome is inherited autosomal dominantly, but typically occurs as a result of a new mutation. If the parents are not clinically affected, a mild phenotype of one parent may be present or a somatic and/or germline mosaic may be observed. The empirical recurrence risk for siblings is otherwise à priori <1%. The DNA-diagnostic yield is above 70%. An inconspicuous genetic finding therefore does not exclude a suspected clinical diagnosis.

Reference: https://www.ncbi.nlm.nih.gov/books/NBK1526/

• Alias: Broad thumbs-hallux syndrome + mental retardation
• Allelic: Bent bone dysplasia syndrome (FGFR2)
• Allelic: Brachydactyly, type D (HOXD13)
• Allelic: Colorectal cancer, somatic (EP300)
• Allelic: Craniofacial-skeletal-dermatologic dysplasia (FGFR2)
• Allelic: Craniosynostosis 1 (TWIST1)
• Allelic: Craniosynostosis, nonspecific (FGFR2)
• Allelic: Encephalocraniocutaneous lipomatosis, somatic mosaic (FGFR1)
• Allelic: Hypogonadotropic hypogonadism 2 with/-out anosmia (FGFR1)
• Allelic: Menke-Hennekam syndrome 1 (CREBBP)
• Allelic: Menke-Hennekam syndrome 2 (EP300)
• Allelic: Polydactyly, postaxial, types A1 + B (GLI3)
• Allelic: Polydactyly, preaxial, type IV (GLI3)
• Allelic: Scaphocephaly and Axenfeld-Rieger anomaly (FGFR2)
• Allelic: Scaphocephaly, maxillary retrusion + mental retardation (FGFR2)
• Allelic: Syndactyly, type V (HOXD13)
• Allelic: Synpolydactyly 1 (HOXD13)
• Allelic: Trigonocephaly 1 (FGFR1)
• Antley-Bixler syndrome without genital anomalies or disordered steroidogenesis (FGFR2)
• Apert syndrome (FGFR2)
• Beare-Stevenson cutis gyrata syndrome (FGFR2)
• Brachydactyly, type E (HOXD13)
• Brachydactyly-syndactyly syndrome (HOXD13)
• Crouzon syndrome (FGFR2)
• Floating-Harbor syndrome (SRCAP)
• Greig cephalopolysyndactyly syndrome (GLI3)
• Hartsfield syndrome (FGFR1)
• Jackson-Weiss syndrome (FGFR1, FGFR2)
• LADD syndrome (FGFR2)(FGFR2)
• Osteoglophonic dysplasia (FGFR1)
• Pallister-Hall syndrome (GLI3)
• Pfeiffer syndrome (FGFR1, FGFR2)
• Robinow-Sorauf syndrome (TWIST1)
• Rubinstein-Taybi syndrome 1 (CREBBP)
• Rubinstein-Taybi syndrome 2 (EP300)
• Saethre-Chotzen syndrome (FGFR2)
• Saethre-Chotzen syndrome with/-out eyelid anomalies (TWIST1)
• Sweeney-Cox syndrome (TWIST1)