85 Pseudoachondroplasia
PSACH, pseudoachondroplastic dysplasia,
pseudoachondroplastic type of spondyloepiphyseal dysplasia
Short limb dwarfism with body proportions resem- bling those of achondroplasia, normal head and face, hypermobility of joints except the elbow, bowed legs or knock-knees
Frequency:Undetermined, possibly 1 in 100,000 births.
Genetics
Autosomal dominant (OMIM 177170), caused by mu- tations in the COMP gene which encodes the carti- lage oligomeric matrix protein and has been mapped to 19p13.1; allelic to multiple epiphyseal dysplasia, Fairbank type (OMIM 132400); parental germinal mosaicism may account for the birth of multiple affected children to unaffected parents.
Clinical Features
• Normal at birth, growth retardation and dispro- portion present by 2 years of age
• Short-limb dwarfism, relatively long trunk (adult height 91.5–137.2 cm)
• Normal head and facies
• Kyphosis, scoliosis, lumbar lordosis
• Limited elbow extension, ulnar deviation of wrists
• Small, broad hands and feet, brachydactyly (saus- age-like fingers)
• Genu valgum, bowed legs, waddling gait
• Normal psychomotor development
• Wide range of severity Differential Diagnosis
• Achondroplasia
• Hypochondroplasia
• Spondyloepiphyseal dysplasia congenita
• Multiple epiphyseal dysplasia
Radiographic Features Spine
• Moderate flattening of vertebrae, anterior tongue- like protrusion of central portion of the vertebral bodies, biconvex deformity of the vertebral bod- ies, irregular vertebral end-plates (in childhood)
• Short pedicles
• Odontoid hypoplasia, atlanto-axial instability (15%)
• Partial restoration of vertebral shape in adulthood
• Kyphoscoliosis, lumbar lordosis (50%) Pelvis
• Small, irregular femoral head epiphyses (early childhood)
• Broad femoral neck, coxa vara
• Widening and delayed development of triradiate cartilage
• Sloping acetabulum with marginal spikes
• Large ilium, short pubis and ischium
• Marked hip dysplasia (in adults) Generalized Bone Defects
• Shortness of tubular bones
• Widened, markedly irregular metaphyses
• Fragmented, irregular, hypoplastic epiphyses
• Distal fibular overlength
• Premature degenerative arthritis (in adults) Hands and Feet
• Short, wide tubular bones, with irregular epiphy- ses
• Rounded proximal ends of metacarpals
• Abnormalities about the carpals (tend to resolve over time)
Chest
• Cupped ribs
Bibliography
Briggs MD, Hoffman SMG, King LM, Olsen AS, Mohrenweiser H, Leroy JG, Mortier GR, Rimoin DL, Lachman RS, Gaines ES, Cekleniak JA, Knowlton RG, Cohn DH. Pseudoachon- droplasia and multiple epiphyseal dysplasia due to muta- tions in the cartilage oligomeric matrix protein gene. Nat Genet 1995; 10: 330–6
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
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Fig. 85.1. Patient 1, 4 years and 6 months. Short limb dwarfism, relatively long trunk, normal head and facies, limited elbow ex- tension, small and broad hands and feet. (Reprint- ed, with permission, from Mastroiacovo et al. 1990)
a b
d e
c
Fig. 85.2. aPatient 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.
bPatient 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
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Fig. 85.3. aPatient 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
c
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
a b
e d
c
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Fig. 85.4. f, g(see previous page for legend)
f g
Fig. 85.5. Patient 5, at 30 years of age. Medial sloping of distal tibia and elongation of distal fibula
Fig. 85.6. aPatient 4, age 3 years. Mild shortening of tubular 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
a b
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
