Roberts Syndrome 849 87 Roberts Syndrome RBS, Roberts-SC phocomelia syndrome, Differential Diagnosis pseudothalidomide syndrome • Thalidomide embryopathy • Baller-Gerold syndrome Tetraphocomelia, cleft lip/palate, ectrodactyly/malpo- • Trisomy 18 sition of thumbs, hypertelorism, exophthalmos • Lethal Nager acrofacial dysostosis • TAR syndrome Frequency: Rare (over 100 cases reported). • DK-phocomelia syndrome • Tetra-amelia with multiple malformations Genetics Autosomal recessive (OMIM 268300); the disease Radiographic Features locus maps to chromosome 8p21; premature cen- Limbs tromere separation; chromosome puffing of hetero- • Asymmetrical reduction anomalies of variable chromatic regions around the centromeres and degree in the long bones of all extremities (90%), nucleolar organizers. ranging from mild hypoplasia to complete aplasia of arms and legs with rudimentary digits; upper Clinical Features extremities usually more involved than lower • Severe growth retardation (pre-/postnatal) extremities, with humerus shorter than femur; • Microcephaly (80%), sparse hair radius usually shorter than ulna • Hypertelorism, prominent eyes, eyelids coloboma, • Humeroradial/humeroulnar synostosis, corneal opacity, cataracts femorotibial synostosis (10%) • Wide nasal bridge, hypoplastic nose, facial hem- • Radial deviation of hands angioma • Oligodactyly, asymmetrical shortening of fingers • Midfacial cleft (80%), usually bilateral cleft lip/ (80%), absent or hypoplastic phalanges (especial- palate, prominent premaxilla, delayed eruption of ly 1st and 5th finger) permanent teeth • Clinodactyly of index finger, soft tissue syndacty- • Dysplastic ears, hypoplastic lobes ly (40%) • Tetramelic, asymmetrical limb reduction, hypo- • Irregular carpal bones, decrease in number of plastic/absent limb bones, oligodactyly, syndacty- carpal bones ly • Clubfoot • Renal dysplasia, polycystic kidneys, heart defects, Skull variable brain malformations, hypogonadism • Microbrachycephaly, oxycephaly, wormian bones, • Thrombocytopenia copper-beaten appearance • Flexion contractions of several joints, including • Maxillary agenesis, cleft palate, frontal defect knees, ankles, wrists, and elbows (50%) (encephalocele) • Orbital hypertelorism • Micrognathia Chest • Fused, thin ribs, abnormal rib number Spine • Spina bifida • Platyspondyly, reduced intervertebral spaces R 850 Roberts Syndrome Fig. 87.1. Patient 1,newborn.Marked growth retardation, mid-facial cleft, pro- minent ocular globes, dysplastic ears, and severe tetramelic limb reduction. (Reprinted, with per- mission, from Mastroiacovo et al. 1990) Bibliography Pavlopoulos PM, Konstantinidou AE, Agapitos E, Davaris P. Cell proliferation rate and nuclear morphometry in Allingham-Hawkins DJ, Tomkins DJ. Heterogeneity in Roberts Roberts syndrome. Clin Genet 1998; 54: 512–6 syndrome. Am J Med Genet 1995; 55: 188–94 Sinha AK, Verma RS, Mani VJ. Clinical heterogeneity of skele- Freeman MVR, Williams DW, Schimke RN, Temtamy SA. The tal dysplasia in Roberts syndrome: a review. Hum Hered Roberts syndrome. Clin Genet 1974; 5: 1–16 1994; 44: 121–6 Mastroiacovo P,Dallapiccola B,Andria G,Camera G,Lungarot- Urban M, Rogalla P,Tinschert S, Krietsch P.Bilaterally cleft lip, ti MS. Difetti congeniti e sindromi malformative. McGraw- limb defects, and haematological manifestations: Roberts Hill, Milan, 1990 syndrome versus TAR syndrome.Am J Med Genet 1998; 79: McDaniel LD, Tomkins DJ, Stanbridge EJ, Somerville MJ, 155–60 Friedberg EC, Schultz RA. Mapping of a single locus capa- Van den Berg DJ,Francke U.Roberts syndrome: a review of 100 ble of complementing the defective heterochromatin phe- cases and a new rating system for severity.Am J Med Genet notype of Roberts syndrome cells. Am J Hum Genet 2005; 1993; 47: 1104–23 77: 132–9.