72 Osteogenesis Imperfecta, Type IIA
OI type IIA, Vrolik disease, thick bone type of lethal neonatal osteogenesis imperfecta
Perinatal death, short-limb dwarfism, deformed ex- tremities, caput membranaceum, multiple fractures at birth
Frequency: See previous section.
Genetics
Autosomal dominant (OMIM 166210), caused by mu- tations of the COL1A1 gene located on chromosome 17q21.31-q22 or of the COL1A2 gene located on chro- mosome 7q22, resulting in disruption of the triple helical assembly and post-translational modification of the two pro-alpha (1) and one pro-alpha (2) chains of type I collagen fibrils; as a result, diminished amount of functionally adequate type I collagen in bone and other mesenchymal tissues; parental ger- minal or somatic mosaicism possible; empiric recur- rence risk 3%.
Clinical Features
• Stillbirth or early perinatal death; polyhydram- nios, fetal hydrops
• Multiple fractures at birth
• Relatively large head, soft cranium, large fon- tanels, multiple palpable wormian bones, hydro- cephalus
• Prominent eyes, blue sclerae
• Small/beaked nose, low nasal bridge, small chin
• Short, bowed, externally rotated limbs fixed at right angles to trunk, relatively normal hands and feet
• Thin skin, inguinal hernias
• Hypotonia, ligamentous laxity Differential Diagnosis
• Other types of OI, especially type IIC (autosomal recessive; very rare; perinatally lethal; thin, poorly modeled, twisted tubular bones with multiple fractures; thin, beaded ribs; relatively normal spine)
• Severe hypophosphatasia
Radiographic Features Generalized Bone Defects
• Generalized osteoporosis
• Multiple fractures at birth, with evidence of callus formation
Skull
• Severely retarded mineralization of calvarium, soft calvarium (caput membranaceum)
• Multiple wormian bones
• Large fontanels Limbs
• Broad, short, crumpled long bones with thin cor- tices
• Rectangular femurs with accordion-like appear- ance and wavy contours
• Angulated tibias and fibulas
Osteogenesis Imperfecta, Type IIA 794
Fig. 72.1. Patient 1, stillborn. Large head, soft cranium, large fontanels, small nose and chin, and short, bowed, and rotated limbs. (Reproduced, with permission, from Mastroiacovo et al.
1990)
Chest
• Short, beaded ribs Spine
• Flat, irregularly deformed vertebrae Pelvis
• Flattened acetabula and iliac wings
Bibliography
Byers PH, Tsipouras P, Bonadio JF, Starman BJ, Schwartz RC.
Perinatal lethal osteogenesis imperfecta (OI type II): a biochemically heterogeneous disorder usually due to new mutations in the genes for type I collagen. Am J Hum Genet 1988; 42: 237–48
Cole WG, Dalgleish R. Perinatal lethal osteogenesis imperfecta.
J Med Genet 1995; 32: 284–9
Gordienko IY, Grechanina EY, Sopko NI, Tarapurova EN, Mikchailets LP. Prenatal diagnosis of osteochondrodys- plasias in high risk pregnancy. Am J Med Genet 1996; 63:
90–7
Mastroiacovo P, Dallapiccola B,Andria G, Camera G, Lungarot- ti MS. Difetti congeniti e sindromi malformative. McGraw- Hill, Milan, 1990
Sillence DO, Barlow KK, Garber AP, Hall JG, Rimoin DL. Osteo- genesis imperfecta type II: delineation of the phenotype with reference to genetic heterogeneity. Am J Med Genet 1984; 17: 407–23
Steinmann B, Rao VH, Vogel A, Bruckner P, Gitzelmann R, Byers PH. Cysteine in the triple-helical domain of one allel- ic product of the alpha 1(I) gene of type I collagen produces a lethal form of osteogenesis imperfecta. J Biol Chem 1984;
259: 11129-38
Thomson EM, Young ID, Hall CM, Pembrey ME. Recurrence risks and prognosis in severe sporadic osteogenesis imper- fecta. J Med Genet 1987; 24: 390–405
Osteogenesis Imperfecta, Type IIA 795
O
Fig. 72.2 a, b. Patient 2, stillborn. Note unossified calvarium;
decreased bone density; broad, short, and crumpled long bones with multiple fractures (observe, in particular, rectan-
gular femurs with wavy contours); thick ribs with continuous beading; small pelvis; and universal flattening of vertebral bodies
a b
