90 Rubinstein-Taybi Syndrome
RTS, Broad thumbs/great toes, characteristic facies, mental retardation
Broad thumbs and halluces, characteristic facies, growth retardation, mental retardation
Frequency: 1 in 125,000 births.
Genetics
Most cases sporadic; autosomal dominant (OMIM 180849) inheritance reported; the disease can be caused by mutations in the gene encoding for the transcriptional coactivator CREB-binding protein, mapped to 16p13.3; genetic heterogeneity demon- strated by mutations in the EP300 gene at chromo- some 22q13.
Clinical Features
• Microcephaly, prominent forehead, hyper- telorism, downward slanting palpebral fissures, long eyelashes, heavy eyebrows, strabismus, ptosis, convex beaked nose, protruding columella, short upper lip, pouting lower lip, hypoplastic maxilla, micrognathia
• Grimacing smile
• Nevus flammeus on forehead, nape, or back (60%), hirsutism (75%)
• Broad thumbs and great toes with angulation, brachydactyly, clinodactyly, polydactyly
• Posterior rotation of ears
• Congenital heart defects (pulmonary stenosis)
• Hyperextensible joints
• Angulated penis (rare), shawl scrotum, cryp- torchidism
• Hypoplastic kidney, renal agenesis, megacolon
• Mental retardation (mainly involving expressive speech), behavioral problems
• CNS defects (corpus callosum agenesis, Dandy- Walker malformation, myelination abnormalities)
• Keloid formation in surgical scars (5–20%)
• Increased risk of developing tumors Differential Diagnosis
• Other syndromes with brachydactyly D
• Floating-Harbor syndrome
• Keipert-Danks syndrome
Radiographic Features Hands and Feet
• Short and wide terminal phalanx of thumbs and great toes, angulation deformities of thumbs and great toes
• ’Delta deformity’ of proximal phalanx of thumbs, notching of terminal phalanx of thumbs
• Short, ovoid 1st metatarsal, deformed or duplicat- ed phalanges of great toes, fused epiphyses of great toes
• Cutaneous syndactyly of toes, postaxial poly- dactyly of toes
• Short, wide, and tufted terminal phalanges of fin- gers
• Clinodactyly of 5th finger
Rubinstein-Taybi Syndrome 856
Fig. 90.1. Patient 1, age 3 years. Microcephaly, long eyelashes, downward slanting palpebral fissures, protruding columella, short upper lips, and micrognathia
Pelvis
• Small iliac index, flared ilia, notched ischia Generalized Bone Defects
• Retarded bone age Skull
• Large foramen magnum
• Prominent forehead
• Large anterior fontanel
• Parietal foramina Spine
• Vertebral anomalies
• Kyphoscoliosis, lordosis
• Spina bifida Chest
• Sternal and rib anomalies Extremities
• Patellar dislocation
• Slipped capital femoral epiphysis
Rubinstein-Taybi Syndrome 857
R
Fig. 90.3. aPatient 3, age 7 years. b, c Patient 4, age 2 months.
R
Note short and wide terminal phalanges of thumbs and marked shortening and widening of great toes, with duplica- tion of proximal and distal phalanges and short, ovoid 1st metatarsals. Both feet are in varus position. (Reprinted, with permission, from Borzani et al. 1980)
a
b
c Fig. 90.2 a, b. Patient 2, age 5 years. Microcephaly, hyper- telorism, ptosis, convex nose, broad angulated thumb, brachy- dactyly, and 5th finger clinodactyly. (From archive of Dr. P.
Balestrazzi, University of Parma, Italy) a
b
Bibliography
Allanson JE: Microcephaly in Rubinstein-Taybi syndrome. Am J Med Genet 1993; 46: 244–6
Berry AC. Rubinstein-Taybi syndrome. J Med Genet 1987; 24:
562–6
Bonioli E, Bellini C, Senes FM, Palmieri A, Di Stadio M, Pinelli G. Slipped capital femoral epiphysis associated with Rubin- stein-Taybi syndrome. Clin Genet 1993; 44: 79–81 Borzani M, Beluffi G, Auriti L, Porzia R, Adamoli L, Carnelli V.
The Rubinstein-Taybi syndrome. Description of 3 new cas- es, with special reference to the radiological aspects. Miner- va Pediatr 1980; 32: 547–54
Petrij F, Giles RM, Dauwerse HG, Saris JJ, Hennekam RCM, Masumo M, Tommerup N, van Ommen GJB, Goodman RH, Peters DJM, Breuning MH. Rubinstein Taybi syndrome caused by mutations in the transcriptional co-activator CBP. Nature 1995; 376: 348–51
Roelfsema JH, White SJ, Ariyurek Y, Bartholdi D, Niedrist D, Papadia F, Bacino CA, den Dunnen JT, van Ommen GJ, Breuning MH, Hennekam RC, Peters DJ. Genetic hetero- geneity in Rubinstein-Taybi syndrome: mutations in both the CBP and EP300 genes cause disease. Am J Hum Genet 2005; 76: 572–80
Stevens CA, Carey JC, Blackburn BL. Rubinstein-Taybi syn- drome: a natural history study. Am J Med Genet (Suppl) 1990; 6: 30–7
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