89 Robinow Syndrome
Robinow Syndrome 853
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 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 reces- sive 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, clin- odactyly, broad thumbs, hypoplastic nails
• Hypoplastic genitalia
• Pectus excavatum
• Cardiac defect, usually right-sided (15% of cases)
• Normal intelligence Differential Diagnosis
• Aarskog syndrome
• Acrodysostosis
• Pseudohypoparathyroidism with severe acro-fa- cial involvement
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Fig. 89.1 a, b. Patient 1, age 12 months. Large head, bulging forehead, flat face, hypertelorism, wide palpebral fissures, de- pressed nasal bridge, mesomelic brachymelia, and hypoplastic genitalia. (Reprinted, with permission, from Canepa et al.
1996) a
b
Robinow Syndrome 854
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)
a b
Fig. 89.3. aPatient 1, age 14 years.
(Reprinted, with permission, from Canepa et al. 1996.) b Patient 3, age 1 year. Note vertebral segmenta- tion defects (hemivertebrae, fused vertebrae) in both these patients.
Patient 3 had undergone cardiac surgery earlier
a b
Radiographic Features Limbs
• Mesomelic brachymelia with disproportionate shortening of forearms
• Ulna shorter than radius, with severe hypoplasia of the distal portion of the ulna
• Radial head luxation (in the recessive form)
• Madelung-like deformity Hands and Feet
• Short phalanges and metacarpals
• Bifid terminal phalanges of thumbs and halluces
• Brachymesophalangy and clinodactyly of 5th digit (85%)
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
Bain MD, Winter RM, Burn J. Robinow syndrome without me- somelic “brachymelia”: a report of five cases. J Med Genet 1986; 23: 350–4
Butler MG, Wadlington WB. Robinow syndrome: report of two patients and review of literature. Clin Genet 1987; 31: 77–85 Canepa G, Maroteaux P, Pietrogrande V. Sindromi dismorfiche e malattie costituzionali dello scheletro. Piccin, Padova, 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 Robinow M. The Robinow (fetal face) syndrome: a continuing
puzzle. Clin Dysmorphol 1993; 2: 189–98
Teebi AS. Autosomal recessive Robinow syndrome. Am J Med Genet 1990; 35: 64–8
van Bokhoven H, Celli J, Kayserili H, van Beusekom E, Balci S, Brussel W, Skovby F, Kerr B, Percin EF, Akarsu N, Brunner HG. Mutation of the gene encoding the ROR2 tyrosine kinase causes autosomal recessive Robinow syndrome. Nat Genet 2000; 25: 423-6
Wadia RS. Recessively inherited costovertebral segmentation defect with mesomelia and peculiar facies (Covesdem syn- drome) – a new genetic entity? J Med Genet 1978; 15: 123–7 Robinow Syndrome 855
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Fig. 89.4 a, b. Patient 1, a at 12 months and b at 14 years of age.
Note marked shortening of tubular bones in the forearm, with ulna shorter than radius (especially distally), and radial head luxation. Also note dorsal bowing of radius with age, resulting in Madelung-like deformity of the forearm. (Reprinted, with permission, from Canepa et al. 1996)
a b
