54 Larsen Syndrome
Multiple congenital joint dislocations, flattened facies, clubfoot
Frequency: 1 per 100,000 births, 1 per 1,500 births in the island of La Réunion in the Indian Ocean.
Genetics
Genetically heterogeneous; usually autosomal reces- sive (OMIM 245600), or autosomal dominant (OMIM 150250); the latter form is caused by mutations in the FLNB gene which maps to 3p21.1-p14.1
Clinical Features
• Short stature
• Multiple congenital joint dislocations
• Flat, round facies, frontal bossing, depressed nasal bridge, hypoplastic midface
• Hypertelorism, cataract
• Cleft soft palate and uvula (30%)
• Mixed hearing loss (20%)
• Lumbar kyphosis
• Brachydactyly, syndactyly, cylindrical fingers, short nails
• Pes cavus, club foot
• Laryngotracheomalacia, laryngeal stenosis
• Intelligence usually normal, mental retardation in 15%
Differential Diagnosis
• Larsen-like joint dislocation, lethal
• Oto-palato-digital syndrome, type 1
• Spondyloepimetaphyseal dysplasia
• Desbuquois syndrome
• SPONASTRIME dysplasia
Radiographic Features Joints
• Multiple dislocations (large joints mostly in- volved) with secondary epiphyseal deformities;
dislocations become less frequent with age
• Bilateral anterior dislocation of radial head (70%)
• Anterior dislocation of tibia on femur (80%)
• Hip dislocation (80%)
• Lateral dislocation of patella
Spine
• Vertebral malsegmentation (cervical and thoracic spine)
• Cervical kyphosis, anterior fusion of C1–2, upper cervical vertebrae dislocation
• Scoliosis, lordosis (thoracic)
• Abnormal odontoid (short, tall, wide), cervical vertebrae hypoplasia
• Narrow interpediculate distance (lumbar)
• Flat vertebrae, irregular end-plates Extremities
• Supernumerary carpal and tarsal bones (extra os- sification center in the calcaneus)
• Short and broad metacarpals, metatarsals, middle and distal phalanges (lack of distal tapering)
• Spatulate thumbs
• Hypoplasia of the distal humerus
• Short fibula, anterior bowing of tibias
• Squared tubular bones
• Finger clubbing
• Talipes equinovarus or equinovalgus (85%)
• Proximal radioulnar synostosis Generalized Bone Defects
• Deficient skeletal mineralization
• Extra ossicles in the hands, wrists, knees, elbows,
• Retarded bone age feet
Skull
• Large neurocranium, small skull base
• Small facial bones
• Shallow orbits, orbital hypertelorism
• Micrognathia Chest
• Thin ribs
• Long clavicles
• Pectus excavatum (10%) Pelvis
• Delayed pubic ossification
Larsen Syndrome 738
Larsen Syndrome 739
L
Fig. 54.1. Patient 1, age 3 months. Flat round face, multiple joint dislocations, with genu recurvatum, and clubfoot.
(Reprinted, with permission, from Mastroiacovo et al. 1990)
Fig. 54.2 a, b. Patient 2, newborn. Note anterior dislocation of both tibias at knee and deformed feet. (Reprinted, with permission, from Peretti et al. 1979)
a
b
Bibliography
Johnston CE, Birch JG, Daniels JL. Cervical kyphosis in pa- tients who have Larsen syndrome. J Bone Joint Surg Am 1996; 78: 538–45
Krakow D, Robertson SP, King LM, Morgan T, Sebald ET, Bertolotto C, Wachsmann-Hogiu S, Acuna D, Shapiro SS, Takafuta T, Aftimos S, Kim CA, Firth H, Steiner CE, Cor- mier-Daire V, Superti-Furga A, Bonafe L, Graham JM Jr, Grix A, Bacino CA, Allanson J, Bialer MG, Lachman RS, Rimoin DL, Cohn DH. Mutations in the gene encoding filamin B disrupt vertebral segmentation, joint formation and skeletogenesis. Nat Genet 2004; 36: 45–10
Latta RJ, Graham CB, Aase JM, Scham SM, Smith DW. Larsen’s syndrome: a skeletal dysplasia with multiple joint disloca- tions and unusual facies. J Pediatr 1971; 78: 291–8 Laville JM, Lakermance P, Limouzy F. Larsen’s syndrome:
review of the literature and analysis of thirty-eight cases.
J Pediatr Orthop 1994; 14: 63–73
Maroteaux P. L’héterogenéité du syndrome de Larsen. Arch Fr Pediatr 1975; 32: 597–603
Mastroiacovo P, Dallapiccola B,Andria G, Camera G, Lungarot- ti MS. Difetti congeniti e sindromi malformative. McGraw- Hill, Milan, 1990
Peretti G, Segrè A, Beluffi GP. Larsen’s syndrome. Case report and discussion. Ital J Orthop Traumatol 1979; 5: 89-96 Petrella R, Rabinowitz JG, Steinmann B, Hirschhorn K. Long-
term follow-up of two sibs with Larsen syndrome possibly due to parental germ-line mosaicism. Am J Med Genet 1993; 47: 187–97
Sugarman GI. The Larsen syndrome, autosomal dominant form. In: Bergsma D (ed.) Malformation syndrome. Na- tional Foundation-March of Dimes, New York, 1975, pp.
121–9
Topley JM, Varady E, Lestringant GG. Larsen syndrome in sib- lings with consanguineous parents. Clin Dysmorphol 1994;
3: 263–5
Vujic M, Hallstensson K, Wahlstrom J, Lundberg A, Langmaack C, Martinsson T. Localization of a gene for autosomal dom- inant Larsen syndrome to chromosome 3p21.1–14.1 in the proximity of, but distinct from, the COL7A1 locus. Am J Hum Genet 1995; 57: 1104–13
Larsen Syndrome 740
Fig. 54.3. Patient 3, age 15 months. Bilateral hip and knee dis- location. Acetabular fossa are shallow and underdeveloped, femoral necks are dysplastic, tibias are anterolaterally dis- placed relative to femurs. Double contour of femurs is ex- plained in original publication, q.v. (Reprinted, with permis- sion, from Peretti et al. 1979)
