9 Atelosteogenesis
AOI, II and III included, giant cell chondrodysplasia (AOI), De la Chapelle syndrome (AOII)
Lethal chondrodysplasia, hypoplastic distal humeri and femurs, hypoplasia of midthoracic spine, lack of ossification of isolated hand bones
Frequency: Very rare.
Genetics
Genetically heterogeneous; AOI, probably autosomal dominant (OMIM 108720); AOII, autosomal recessive same as de la Chapelle dysplasia (OMIM 256050), due to mutation of the diastrophic dysplasia sulfate- transporter (DTDST) gene SLC26A2; AOIII, probably autosomal dominant (OMIM 108721), all cases iso- lated; advanced paternal age.
Clinical Features in AOI
• Polyhydramnios
• Lethal chondrodysplasia with rhizomelic short limbs
• Early death form respiratory distress
• Elbow or knee subluxation
• Distal humeral and femoral hypoplasia
• Clubfeet
• Giant chondrocytes in the reserve-zone cartilage matrix
Clinical Features in AOII
• Lethal short limb dysplasia with deficient ossifica- tion of parts of the skeleton
• Dysmorphic, flat face, cleft palate, micrognathia
• Bowed long bones
• Large joint dislocations
• Abducted thumbs and toes (hitchhiker), clubfeet
• Small chest, short ribs, pulmonary hypoplasia
• Stenosis of the larynx, bronchomalacia
• Cervical kyphosis, severe lumbar hyperlordosis Clinical Features in AOIII
• Milder, usually nonlethal bone dysplasia, with fea- tures overlapping those of AOI and AOII
• Short-limb dwarfism, bowed limbs
• Hypertelorism, flat nasal bridge, micrognathia, often cleft palate
• Narrow chest
• Multiple joints dislocations
• Hand and foot anomalies
Differential Diagnosis
• AOI: Boomerang syndrome and AOIII
• AOII: Pseudodiastrophic dysplasia and diastroph- ic dysplasia
• AOIII: Oto-palato-digital type II syndrome, some overlap with Larsen syndrome
Radiographic Features in AOI Extremities
• Absent, segment-shaped, or distally tapering humeri
• Short, club-shaped femurs with distal tapering
• Short radius and ulna
• Bowed tibias
• Absent/hypoplastic fibulas Hands and Feet
• Dysharmonic ossification of tubular bones of hands and feet: hypoplasia of the metacarpals and metatarsals; marked hypoplasia or absence of proximal and middle phalanges; and well-ossified, short, wide distal phalanges
• Clubfeet Pelvis
• Hypoplasia of ischiopubic bones
• Flared ilia,with hypoplasia of their basilar portion Spine
• Coronal (and sagittal) clefts (lumbar spine)
• Segmentation defects
• Platyspondyly, vertebral hypoplasia (thoracic)
• Scoliosis Chest
• Elongated clavicles
• Eleven pairs of short ribs
Radiographic Features in AOII Extremities
• Short, distally pointed or bifid humeri
• Short, club-shaped femurs
• Short radius and ulna (distal hypoplasia of ulna, proximal hypoplasia of radius)
• Hypoplastic, bowed tibias
• Hypoplastic,often pointed (proximally or distally) fibulas
Hands and Feet
• Much more irregular ossification of tubular bones than in AOI: absence of some bones, and presence of supernumerary bones
A
thumbs and great toes)
• Elongated 2nd and 3rd metacarpals
• Rounded hypoplastic middle phalanges
• Gap between 1st and 2nd digits Spine
• Platyspondyly
• Cervical kyphosis, lordosis, scoliosis (S-shaped cervical spine)
• Coronal clefts (not mandatory) Pelvis
• Short, flared ilia
• Horizontal acetabula, with spike-like projection at the medial border
Chest
• Short ribs
• Thin clavicles
• Small scapulae
Radiographic Features in AOIII Extremities
• Distal tapering of humeri and femurs
• Absent/hypoplastic fibulas
• Short tibias
• Tombstone-shaped proximal phalanges
• Irregular shortening of metacarpals and metatarsals
• Widened distal phalanges
• Bifid digits
• Syndactyly, polydactyly Spine
• Double-curve configuration of cervical spine
• Coronal clefts Pelvis
• Hypoplastic ischiopubic bones, vertical block-like ischia, and ‘banana-shaped’ pubic rami
Skull
• Hypoplastic facial bones, maxilla and mandible
• Prominent occiput
Bibliography
Canepa G, Maroteaux P, Pietrogrande V. Sindromi dismorfiche e malattie costituzionali dello scheletro. Piccin, Padova, 1996
Hastbacka J, Superti-Furga A, Wilcox WR, Rimoin DL, Cohn DH, Lander ES. Atelosteogenesis type II is caused by muta- tions in the diastrophic dysplasia sulfate-transporter gene (DTDST): evidence for a phenotypic series involving three chondrodysplasias. Am J Hum Genet 1996; 58: 255–62 Kozlowski K, Bateson EM. Atelosteogenesis. Rofo Fortschr Geb
Rontgenstr Nuklearmed 1984; 140: 224–5
1982; 13: 15–25
Mastroiacovo P, Dallapiccola B,Andria G, Camera G, Lungarot- ti MS. Difetti congeniti e sindromi malformative. McGraw- Hill, Milan, 1990
Nores JA, Rotmensch S, Romero R, Avila C, Inati M, Hobbins JC: Atelosteogenesis type II: sonographic and radiological correlation. Prenat Diagn 1992; 12: 741–53
Newbury-Ecob R. Atelosteogenesis type 2. J Med Genet 1998;
35: 49–53
Rossi A, van der Harten HJ, Beemer FA, Kleijer WJ, Gitzelmann R, Steinmann B, Superti-Furga A. Phenotypic and genotyp- ic overlap between atelosteogenesis type 2 and diastrophic dysplasia. Hum Genet 1996; 98: 657–61
Sillence D, Worthington S, Dixon J, Osborn R, Kozlowski K.
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Fig. 9.1. Patient 1, stillborn. Flat face, severe rhizomelic limb shortening, narrow chest, protuberant abdomen, and clubfeet.
(Reprinted, with permission, from Mastroiacovo et al. 1990)
A
Fig. 9.2. aPatient 2, AOI in a stillborn. Rhizomelic limb short- ening, with short, distally tapering humeri, and short, club- shaped femurs. Note that radius is shorter than ulna. Also note bowed tibias, absent fibulas, elbow and knee dislocations, clubfeet, flared ilia, hypoplastic basilar portions of ilia, absent ossification of pubic rami, and grossly deficient ossification of vertebrae (Reprinted, with permission, from Canepa et al.
1996. Original case provided by M.P. Cordier). b Patient 3, AOI in another stillborn. Severely shortened, round humeri; short, club-shaped femurs; hypoplastic radius, bowed tibiae, absent fibulae, knee dislocation, and deficient ossification of pubic bones. (Reprinted, with permission, from Canepa et al. 1996.
Original case provided by F. Giraud)
a b
a b c
e d
Fig. 9.4. aAOI. Note flared ilium with deficiency of its basilar portion. b AOII. Reduced superoinferior diameter of ilium, and horizontal acetabulum with medial spur. c AOIII. Flaring of iliac wing, and steep acetabulum. (Reprinted, with permission, from Sillence et al. 1997)
a b c
Fig. 9.3. a AOI. Note vertebral hypo- plasia and coronal clefts in the lumbar spine. b–d AOII. Different degrees of spinal involvement. Observe marked cervical kyphosis in d. e AOIII. The ver- tebral bodies are small, with coronal clefts in the lower lumbar spine.
(Reprinted, with permission, from Sil- lence et al. 1997)
A
Fig. 9.5. aAOI. Note short, distally tapered femur. b, c AOII. The femur is short, with expanded club-like end in b. Proximal taper- ing of femur is observed in a se- verely affected baby in c. d AOIII.
The femur is short, with distal tapering. (Reprinted, with permis- sion, from Sillence et al. 1997)
a b
d c
b, cAOII. The humerus is distally tapered in b and characteristi- cally bifurcated, V-shaped in c.
d AOIII. Note disproportionately short, distally tapered humerus.
(Reprinted, with permission, from Sillence et al. 1997)
a b
d c
Fig. 9.7. aAOI. Note striking ossification of distal phalanges, in sharp contrast with absence or severely deficient ossifica- tion of middle and proximal phalanges. b AOII. Tubular bones in the hand are short and grossly distorted, with supernumer- ary bones, globular 1st metacarpal, and characteristic hitch-
hiker thumb. c AOIII. Note varying degrees of metacarpal shortening, with squared metacarpal appearance. The pha- langes are short and broad, with convex proximal and distal margins. (Reprinted, with permission, from Sillence et al.
1997)
a b c
