838 Pseudoachondroplasia 85 Pseudoachondroplasia PSACH, pseudoachondroplastic dysplasia, Radiographic Features pseudoachondroplastic type of spondyloepiphyseal Spine dysplasia • Moderate flattening of vertebrae, anterior tongue- like protrusion of central portion of the vertebral Short limb dwarfism with body proportions resem- bodies, biconvex deformity of the vertebral bod- bling those of achondroplasia, normal head and face, ies, irregular vertebral end-plates (in childhood) hypermobility of joints except the elbow, bowed legs or • Short pedicles knock-knees • Odontoid hypoplasia, atlanto-axial instability (15%) Frequency:Undetermined,possibly 1 in 100,000 births. • Partial restoration of vertebral shape in adulthood • Kyphoscoliosis, lumbar lordosis (50%) Genetics Pelvis Autosomal dominant (OMIM 177170),caused by mu- • Small, irregular femoral head epiphyses (early tations in the COMP gene which encodes the carti- childhood) lage oligomeric matrix protein and has been mapped • Broad femoral neck, coxa vara to 19p13.1; allelic to multiple epiphyseal dysplasia, • Widening and delayed development of triradiate Fairbank type (OMIM 132400); parental germinal cartilage mosaicism may account for the birth of multiple • Sloping acetabulum with marginal spikes affected children to unaffected parents. • Large ilium, short pubis and ischium • Marked hip dysplasia (in adults) Clinical Features Generalized Bone Defects • Normal at birth, growth retardation and dispro- • Shortness of tubular bones portion present by 2 years of age • Widened, markedly irregular metaphyses • Short-limb dwarfism, relatively long trunk (adult • Fragmented, irregular, hypoplastic epiphyses height 91.5–137.2 cm) • Distal fibular overlength • Normal head and facies • Premature degenerative arthritis (in adults) • Kyphosis, scoliosis, lumbar lordosis Hands and Feet • Limited elbow extension, ulnar deviation of wrists • Short, wide tubular bones, with irregular epiphy- • Small, broad hands and feet, brachydactyly (saus- ses age-like fingers) • Rounded proximal ends of metacarpals • Genu valgum, bowed legs, waddling gait • Abnormalities about the carpals (tend to resolve • Normal psychomotor development over time) • Wide range of severity Chest • Cupped ribs Differential Diagnosis • Achondroplasia • Hypochondroplasia • Spondyloepiphyseal dysplasia congenita • Multiple epiphyseal dysplasia Pseudoachondroplasia 839 Fig. 85.1. Patient 1, 4 years Bibliography and 6 months. Short limb dwarfism, relatively long Briggs MD, Hoffman SMG, King LM, Olsen AS, Mohrenweiser trunk, normal head and H, Leroy JG, Mortier GR, Rimoin DL, Lachman RS, Gaines facies, limited elbow ex- ES, Cekleniak JA, Knowlton RG, Cohn DH. Pseudoachon- tension, small and broad droplasia and multiple epiphyseal dysplasia due to muta- hands and feet. (Reprint- tions in the cartilage oligomeric matrix protein gene. Nat ed, with permission, from Genet 1995; 10: 330–6 Mastroiacovo et al. 1990) Hecht JT, Nelson LD, Crowder E, Wang Y, Elder FFB, Harrison WR, Francomano CA, Prange CK, Lennon GC, Deere M, Lawler J. Mutations in exon 17B of cartilage oligomeric matrix protein (COMP) cause pseudoachondroplasia. Nat Genet 1995; 10: 325–9 Kopits SE,Lindstrom JA,McKusick VA.Pseudoachondroplastic dysplasia: pathodynamics and management.In: Bergsma D (ed.) Skeletal dysplasias. Excerpta Medica, Amsterdam, 1974, pp. 341–52 McKeand J, Rotta J, Hecht JT. Natural history study of pseudo- achondroplasia. Am J Med Genet 1996; 63: 406–10 Maroteaux P, Stanescu R, Stanescu V, Fontaine G. The mild form of pseudoachondroplasia. Identity of the morpholog- ical and biochemical alterations of growth cartilage with those of typical pseudoachondroplasia. Eur J Pediatr 1980; 133: 227–31 Maroteaux P,Lamy M. Les formes pseudo-achondroplastiques des dysplasies spondylo-epiphysaires. Presse Med 1959; 67: 383–6 Mastroiacovo P,Dallapiccola B,Andria G,Camera G,Lungarot- ti MS. Difetti congeniti e sindromi malformative. McGraw- Hill, Milan, 1990 Wynne-Davies R, Hall CM, Young ID. Pseudoachondroplasia: clinical diagnosis at different ages and comparison of auto- somal dominant and recessive types. A review of 32 pa- tients (26 kindreds). J Med Genet 1986; 23: 425–34 P 840 Pseudoachondroplasia Fig. 85.2. a Patient 2, age 7 years. Mild platyspondyly, with slight irregulari- ty of vertebral end-plates. Interpediculate distance does not increase cephalocaudally. Note significant cupping of posterior ends of the ribs. b Patient 2, age 7 years. Dens is clearly separated from body of odontoid and displaced anteriorly. Atlanto-axial joint is unstable. c Patient 3, age 5 years. Vertebral bodies show a biconvex configuration of end-plates, and anterior ‘tonguing,’ most prominent in the lumbar vertebrae. d Patient 4, age 3 years. Severe tongue-like deformity of central portions of vertebral bodies. e Patient 5, at 27 years of age. Minimal irregularities of the vertebral end-plates may be explained either by wide range of phenotypic variability of this disease or by improvement known to occur in spinal changes with age ab c de Pseudoachondroplasia 841 Fig. 85.3. a Patient 2, age 7 years. Markedly small and irregular cap- ital femoral epiphyses associated with underdeveloped basilar por- tions of ilia and irregularities of acetabula, and of pubic and ischial bones. b, c Patient 5, b at 16 years and c at 30 years, illustrating pro- gression of changes in femoral heads over time, resulting in frag- mentation and severe coxa vara deformity on both sides a b P c 842 Pseudoachondroplasia Fig. 85.4. a, b Patients a 4 (age 3 years) and b 3 (age 5 years): overall changes in lower extremi- ties, including shortening of tubu- lar bones, irregularity of metaphy- ses, and smallness of epiphyses, are mild. c Patient 2, age 7 years: severe metaphyseal irregularity is seen, most prominent at the level of the tibial plateaux. Epiphyses are small, those at distal femur have partially migrated into cor- responding metaphyses. d–g Pa- tient 5, d, e at 14 years of age and f, g at 30 years of age (see next page): severe changes around knees, with partial recovery in adult life. Metaphyses are wide, and markedly irregular, whereas epiphyses are fragmented and dysplastic ab c d e Pseudoachondroplasia 843 Fig. 85.4. f, g (see previous page for legend) fg ab P Fig. 85.5. Patient 5, at 30 years of age. Medial sloping of distal Fig. 85.6. a Patient 4, age 3 years. Mild shortening of tubular tibia and elongation of distal fibula bones in upper extremity and metaphyseal widening with lateral spur formation are seen in this child. b Patient 5, at 30 years of age. Humerus is short and wide, with expansion of the proximal metaphysis and marked hypoplasia of corre- sponding epiphysis, a relatively constant finding in this disease 844 Pseudoachondroplasia Fig. 85.7. a, b. Patient 2, age 7 years. a Tubular bones in hands are short, broad, with expanded irreg- ular metaphyses, and small dys- plastic epiphyses. Ossification of carpal bones is delayed. Signs of metaphyseal and epiphyseal dys- plasia are also evident at distal ra- dius and ulna.b Similar changes to those described in the hands are also seen in the feet.Note irregular and fragmented tarsal bones, short tubular bones, and dysplas- tic epiphyses a b.