89 Robinow Syndrome R

Robinow Syndrome 853 89 Robinow Syndrome Fetal face syndrome, mesomelic dysplasia Robinow type Characteristic facies, mesomelic shortening of upper limbs, short fingers, hypoplastic genitalia Frequency: 1 in 500,000 births, possibly more com- mon in Czechoslovakia than elsewhere; over 80 cases reported. Genetics Autosomal dominant (OMIM 180700); paternal age effect; autosomal recessive form (OMIM 268310), more severe (costovertebral segmentation defects with mesomelia or COVESDEM), caused by homo- zygous mutations in the ROR2 (receptor tyrosine a kinase-like orphan receptor 2) gene, which has been mapped to 9q22 (allelic to autosomal dominant brachydactyly B). Clinical Features • Moderate short stature (more severe in the recessive form) • Characteristic facies, resembling that of a fetus at 8 weeks: disproportionately large neurocranium with bulging forehead, flat face, hypertelorism, wide palpebral fissures, S-shaped lower lids, and short nose with depressed nasal bridge and ante- verted nares (fetal face: features become less strik- ing in older patients) • Long philtrum (in the dominant form), short philtrum (in the recessive form), triangular mouth, gingival hyperplasia, malaligned teeth, micrognathia • Mesomelic brachymelia of upper limbs (more severe in the recessive form), brachydactyly, clinodactyly, broad thumbs, hypoplastic nails • Hypoplastic genitalia • Pectus excavatum • Cardiac defect, usually right-sided (15% of cases) • Normal intelligence Differential Diagnosis • Aarskog syndrome b R • Acrodysostosis Fig. 89.1 a,b. Patient 1, age 12 months. Large head, bulging • Pseudohypoparathyroidism with severe acro-fa- forehead, flat face, hypertelorism, wide palpebral fissures, de- cial involvement pressed nasal bridge, mesomelic brachymelia, and hypoplastic genitalia. (Reprinted, with permission, from Canepa et al. 1996) 854 Robinow Syndrome a b Fig. 89.2 a,b. Patient 2, 2 years. Skull is enlarged relative to facial bones, and the forehead is prominent. Hypertelorism and flat facial bones with mandibular hypoplasia. (Courtesy of Dr. GP Beluffi, University of Pavia, Italy) Fig. 89.3. a Patient 1, age 14 years. (Reprinted, with permission, from Canepa et al. 1996.) b Patient 3, age 1 year. Note vertebral segmentation defects (hemivertebrae, fused vertebrae) in both these patients. Patient 3 had undergone cardiac surgery earlier ab Robinow Syndrome 855 Chest • Multiple rib anomalies (35%), rib fusions (in the recessive form) Spine • Hemivertebrae, fused vertebrae (65%), scoliosis (50%) (in the recessive form) • Narrow interpediculate distance Skull • Large skull, with prominent forehead • Flattened facial bones • Small mandible • Ocular hypertelorism Bibliography Afzal AR, Rajab A, Fenske CD, Oldridge M, Elanko N, Ternes- Pereira E, Tuysuz B, Murday VA, Patton MA, Wilkie AO, Jeffery S. Recessive Robinow syndrome, allelic to dominant brachydactyly type B, is caused by mutation of ROR2. Nat Genet 2000; 25: 419-22 Ayme S, Preus M. Spondylocostal/spondylothoracic dysosto- sis: the clinical basis for prognosticating and genetic coun- seling. Am J Med Genet 1986; 24: 599–606 ab Bain MD, Winter RM, Burn J. Robinow syndrome without mesomelic “brachymelia”: a report of five cases. J Med Genet Fig. 89.4 a,b. Patient 1, a at 12 months and b at 14 years of age. 1986; 23: 350–4 Note marked shortening of tubular bones in the forearm, with Butler MG,Wadlington WB. Robinow syndrome: report of two ulna shorter than radius (especially distally), and radial head patients and review of literature. Clin Genet 1987; 31: 77–85 luxation. Also note dorsal bowing of radius with age, resulting Canepa G, Maroteaux P,Pietrogrande V.Sindromi dismorfiche in Madelung-like deformity of the forearm. (Reprinted, with e malattie costituzionali dello scheletro. Piccin, Padova, permission, from Canepa et al. 1996) 1996 Israel H, Johnson GF. Craniofacial pattern similarities and ad- ditional orofacial findings in siblings with the Robinow syndrome. J Craniofac Genet Dev Biol 1988; 8: 63–73 Radiographic Features Robinow M. The Robinow (fetal face) syndrome: a continuing puzzle. Clin Dysmorphol 1993; 2: 189–98 Limbs Teebi AS. Autosomal recessive Robinow syndrome. Am J Med • Mesomelic brachymelia with disproportionate Genet 1990; 35: 64–8 shortening of forearms van Bokhoven H, Celli J, Kayserili H, van Beusekom E, Balci S, • Ulna shorter than radius, with severe hypoplasia Brussel W, Skovby F, Kerr B, Percin EF, Akarsu N, Brunner of the distal portion of the ulna HG. Mutation of the gene encoding the ROR2 tyrosine • kinase causes autosomal recessive Robinow syndrome. Nat Radial head luxation (in the recessive form) Genet 2000; 25: 423-6 • Madelung-like deformity Wadia RS. Recessively inherited costovertebral segmentation Hands and Feet defect with mesomelia and peculiar facies (Covesdem syn- • Short phalanges and metacarpals drome) – a new genetic entity? J Med Genet 1978; 15: 123–7 • Bifid terminal phalanges of thumbs and halluces • Brachymesophalangy and clinodactyly of 5th digit (85%) R.

Load more