79 Oto-palato-digital Syndrome, Type II
Oto-palato-digital Syndrome, Type II 819
OPD II, cranio-oro-digital syndrome
Short stature, unusual facies, cleft palate, multiple skeletal anomalies
Frequency: Rare (fewer than 50 published cases).
Genetics
X-linked semidominant (OMIM 304120), caused by gain-of-function mutations in the gene encoding filamin A (FLNA), mapped to chromosome Xq28;
allelic to OPD1.
Clinical Features
• Microcephaly, frontal bossing, lateral fullness of supraorbital ridges, large anterior fontanel
• Midface hypoplasia, short, stubby, nose, broad nasal bridge
• Hypertelorism, down-slanting palpebral fissures
• Small mouth, high-arched palate, cleft palate (80% of affected males), bifid uvula, marked micrognathia
• Low-set ears, conductive deafness
• Small thorax
• Omphalocele, hypospadias, hydronephrosis
• Curved long bones
• Flexed overlapping fingers, short thumbs, broad fingertips, clinodactyly, syndactyly
• Multiple joint dislocations
• Short hallux
• Occasionally, mental retardation
• Many female carriers have a normal facies or mild midface abnormalities
Differential Diagnosis
• Oto-palato-digital syndrome type 1
• Larsen syndrome
• Atelosteogenesis types I and III
• Boomerang dysplasia
• Melnick-Needles syndrome
• Camptomelic dysplasia
Radiographic Features Extremities
• Anterolateral bowing of long bones, with apex at the midshaft (curvature may disappear early in life)
• Hypoplastic or absent fibulas (70%)
• Elbow dislocation
• Broad metaphyses
• Increased density of long bones at the midshaft Hands and Feet
• Very short, broad thumbs and great toes
• Abnormal epiphyses of proximal phalanges of hands
• Hypoplastic, irregular metacarpals/metatarsals, and phalanges of fingers and toes
• Clinodactyly of the 2nd finger
• Polydactyly (postaxial)
• Syndactyly (cutaneous or osseous) in the fingers and toes
• Transverse capitate bone
• Clubfoot Skull
• Skull base hyperostosis, prominent forehead, pro- minent supraorbital ridge
• Reduced ossification of the cranial vault, late closure of anterior fontanel, wide sutures
• Midface hypoplasia
• Vertical clivus
• Micrognathia (obtuse mandibular angle) Joints
• Multiple joint dislocations (elbow, wrist, knee, hip)
Chest
• Narrow thorax with short, thin, wavy ribs
• Thin, wavy, sloping clavicles
• Pectus excavatum, accelerated sternal ossification
• Wavy lateral borders of scapulae Spine
• Flat vertebrae
• Exaggerated widening of lumbosacral spinal canal
• Scoliosis Pelvis
• Small ilia, with lack of normal flaring
• Flat acetabular roof
• Vertical ischia
• Poorly developed pubic bones
• Coxa valga
O
Oto-palato-digital Syndrome, Type II 820
Fig. 79.1. a–d Patient 1: male infant at 34 weeks’ gestation, who died soon after birth. a Note small mouth with down-turned bow of upper lips, severe micrognathia with prominent chin creases, broad nose, ocular hypertelorism, and frontal bossing. b AP radiograph of the pelvis and lower limbs, showing flared iliac wings, flat acetabular roofs, vertical ischia, absent pubic bones, bowed femurs and tibias, and absent fibulas. c, d AP radiograph and line drawing of the feet, showing decreased metatarsal and phalangeal ossification with four- toed (‘tree-frog’) configuration. e Patient 2: mother of patient 1. Note hypertelorism and down-slanting palpebral fissures. (Reprinted, with permission, from Savarirayan et al. 2000)
a
c
e
b
d
Oto-palato-digital Syndrome, Type II 821
O
Fig. 79.2 a–d. Patient 3: male infant at 36 weeks’ gestation, who died of respiratory distress soon after birth. a, b Note hyper- telorism, down-slanting palpebral fissures, flat and broad nose, cleft lip, small omphalocele, and ‘tree-frog’ toes. c, d Note
small thorax with wavy ribs, bowed femurs, severe micro- gnathia, and coronal cleft vertebrae in lumbar spine. (Reprint- ed, with permission, from Savarirayan et al. 2000)
a b
c d
Bibliography
Brewster TG, Lachman RS, Kushner DC, Holmes LB, Isler RJ, Rimoin DL. Oto-palato-digital syndrome, type II – an X- linked skeletal dysplasia. Am J Med Genet 1985; 20: 249–54 Corona-Rivera JR, Corona-Rivera E, Corona-Rivera A, Quiles- Corona M, Velez-Gomez E, Arana-Gutierrez MA. Infant with manifestations of oto-palato-digital syndrome type II and of Melnick-Needles syndrome. Am J Med Genet 1999;
85: 79–81
Gendall PW, Kozlowski K. Oto-palato-digital syndrome type II. Report of two related cases. Pediatr Radiol 1992; 22:
267–9
Holder SE, Winter RM. Otopalatodigital syndrome type II.
J Med Genet 1993; 30: 310–3
Kozlowski K, Turner G, Scougall J, Harrington J. Oto-palato- digital syndrome with severe X-ray changes in two half brothers. Pediatr Radiol 1977; 6: 97–102
Nishimura G, Horiuchi T, Kim OH, Sasamoto Y. Atypical skele- tal changes in otopalatodigital syndrome type II: pheno- typic overlap among otopalatodigital syndrome type II, boomerang dysplasia, atelosteogenesis type I and type III, and lethal male phenotype of Melnick-Needles syndrome.
Am J Med Genet 1997; 73: 132–8
Robertson SP, Walsh S, Oldridge M, Gunn T, Becroft D, Wilkie AO. Young K, Barth CK, Moore C, Weaver DD. Linkage of otopalatodigital syndrome type 2 (OPD2) to distal Xq28:
evidence for allelism with OPD1. Am J Hum Genet 2001; 69:
223-7
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
Savarirayan R, Cormier-Daire V, Unger S, Lachman RS, Rough- ley PJ, Wagner SF, Rimoin DL, Wilcox WR. Oto-palato-digi- tal syndrome, type II: report of three cases with further delineation of the chondro-osseous morphology. Am J Med Genet 2000; 95: 193-200
Young K, Barth CK, Moore C,Weaver DD. Otopalatodigital syn- drome type II associated with omphalocele: report of three cases. Am J Med Genet 1993; 45: 481–7
Oto-palato-digital Syndrome, Type II 822
Fig. 79.3. Patient 4: Male infant at 34 weeks’ gestation; brother of patient 3. Note dysharmonic ossification with severe hypo- plasia of all metacarpals (especially the 1st), hypoplastic mid- dle phalanges, broad proximal and distal phalanges, and clenched fingers. (Reprinted, with permission, from Savari- rayan et al. 2000)
