78 Oto-palato-digital Syndrome, Type I
OPDI, Taybi syndrome
Cleft palate, downward slanted palpebral fissures, conductive hearing loss, spatulate thumb/hallux, ir- regular digits
Frequency: Rare (about 50 published cases).
Genetics
X-linked semi-dominant with variable, usually mild, expression in females (OMIM 311300); caused by gain-of-function mutations in the FLNA gene, mapped to Xq28; allelic to OPDII.
Clinical Features
• Short stature
• Prominent occiput, flat midface, frontal bossing, prominent supraorbital ridges, hypertelorism, downward slanted palpebral fissures, telecanthus, broad nasal root (pugilistic appearance)
• Cleft palate, hypodontia
• Conductive hearing loss
• Pectus excavatum
• Scoliosis
• Short, spatulated thumbs, 5th finger clinodactyly
• Short halluces, syndactyly/clinodactyly of other toes, widely spaced toes
• Mild mental retardation Differential Diagnosis
• Larsen syndrome
• Oto-palato-digital syndrome, type 2
• Frontometaphyseal dysplasia
Radiographic Features Skull
• Skull thickening, especially frontal bones and base of anterior fossa (mushroom-like appearance)
• Absent/deficient pneumatization of frontal and sphenoid sinuses, hypoplastic paranasal sinuses and mastoids
• Hypoplastic facial bones
• Micrognathia, increased mandibular angle
• Abnormally vertical clivus
• Prominent occipital bones Hands and Feet
• Short, broad, and flattened terminal phalanges
• Supernumerary carpal bones, carpal bone fusion (mostly capitate-hamate)
• Shortening of radial side of 5th middle phalanx, resulting in clinodactyly of 5th finger
• Proximal elongation of 2nd metacarpal (especially its ulnar side), with prominent pseudoepiphysis
• Global shortening of the great toe
• Multiple fusions between metatarsals (2nd and 3rd) and tarsal bones (cuneiform and navicular)
• Proximal elongation of the 5th metatarsal, with accessory proximal ossification center
Extremities
• Hypoplastic proximal radius, with radial head dis- location
• Deepened fossa at proximal ulna Spine
• Anterior displacement of C-1 and C-2 relative to the clivus
• Exaggeration of normal craniocaudal increase in interpediculate distance
• Schisis of neural arches Pelvis
• Small ilia with lack of normal flaring
• Broad ischia
• Mild coxa valga
Oto-palato-digital Syndrome, Type I 814
O
Fig. 78.1 a–e. aPatient 1, age 12 years (From archive of Dr.
P. Balestrazzi, University of Parma, Italy, with permission);
b, c patient 2, age 18 months (Reprinted, with permission, from Pazzaglia and Beluffi 1986); d, e patient 3, age 9 years (first cousin of patient 2) (Reprinted, with permission, from
Pazzaglia and Beluffi 1986). Frontal bossing, prominent supra- orbital ridges, asymmetrical and downward slanted palpebral fissures, telecanthus, and broad nasal root (pugilistic appear- ance). Note small mouth with down-turned corners and pec- tus excavatum in b and d, and hypoplastic jaw in c and e
a b
d e
c
Oto-palato-digital Syndrome, Type I 816
Fig. 78.2. Patient 1, age 12 years. a Cutaneous syndactyly of fingers 2 and 3; b widely spaced 1st and 2nd toes. (From archive of Dr. P. Balestrazzi, University of Parma, Italy, with permission)
a
b
Fig. 78.3. Patient 2, age 18 months.
Note striking increase in the inter- pedicular distance in the lumbar spine, narrow lumbar pedicles, and failure of osseous fusion of the neural arches. (Reprinted, with permission, from Pazzaglia and Beluffi 1986)
Fig. 78.4. Patient 2, age 18 months. Ilia are narrow, with lack of normal flaring of iliac wings; ischial bones are relatively broad.
(Reprinted, with permission, from Pazzaglia and Beluffi 1986)
Bibliography
Biancalana V, Le Marec B, Odent S, van den Hurk JAM, Hanauer A. Oto-palato-digital syndrome type I: further evidence for assignment of the locus to Xq28. Hum Genet 1991; 88: 228–30
Gall JC, Stern AM, Poznanski AK, Garn SM, Weinstein ED, Hayward JR. Oto-palato-digital syndrome: comparison of clinical and radiographic manifestations in males and females. Am J Hum Genet 1972; 24: 24–36
Hoar DI, Field LL, Beards F, Hoganson G, Rollnick B. Tentative assignment of gene for oto-palato-digital syndrome to distal Xq (Xq26-q28). Am J Med Genet 1992; 42: 170–2 Langer LO. The roentgenographic features of the oto-palato-
digital (OPD) syndrome. AJR Am J Roentgenol 1967; 100:
63–70
Pazzaglia UE, Beluffi G. Oto-palato-digital syndrome in four generations of a large family. Clin Genet 1986; 30: 338–44
Poznanski AK, Macpherson RI, Dijkman DJ, Gorlin RJ, Gall JC, Stern AM, Garn SM, Nagy JM. Otopalatodigital syndrome:
radiologic findings in the hand and foot. Birth Defects Orig Art Ser 1974; 10: 125–39
Robertson SP, Twigg SR, Sutherland-Smith AJ, Biancalana V, Gorlin RJ, Horn D, Kenwrick SJ, Kim CA, Morava E, New- bury-Ecob R, Orstavik KH, Quarrell OW, Schwartz CE, Shears DJ, Suri M, Kendrick-Jones J, Wilkie AO; OPD-spec- trum Disorders Clinical Collaborative Group. Localized mutations in the gene encoding the cytoskeletal protein fil- amin A cause diverse malformations in humans. Nat Genet 2003; 33: 487–91
Suzumura H, Kano K, Nishimura G. Hypoplasia of the trans- verse sinus in oto-palato-digital syndrome type I. Am J
Med Genet 1998; 79: 401–2 O
Fig. 78.5. a Patient 2,age 18 months; b patient 3, age 9 years. Note short, broad distal phalanges, with ‘truncated’ appearance;
proximal elongation of the 2nd metacarpal on its ulnar side;
and clinodactyly of the 5th finger. In patient 3 (b) the elongat-
ed, proximal portion of the 2nd metacarpal is fused with the trapezoid, the long axis of the capitate is in a transverse orien- tation and there is partial fusion of some carpal bones a
b
Oto-palato-digital Syndrome, Type I 818
Fig. 78.6. Patient 3, age 9 years. Note short phalanges and metatarsal of the great toe, proximal elongation of the 2nd and 3rd metatarsals due to fusion with the deformed cuneiforms, and synostosis between 1st cuneiform and navicular bones
