SPONDYLOEPIPHYSEAL DYSPLASIA CONGENITA
 
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SPONDYLOEPIPHYSEAL DYSPLASIA CONGENITA

 

DEFINITION:

A non-lethal form of congenital dwarfism characterized by typical skeletal dysplasias (micromelia), vertebral changes, and ocular manifestations.

EPIDEMIOLOGY:

  • incidence: rare
  • age of onset:
    • newborn
  • risk factors:
    • familial - autosomal dominant (with variable expressivity and high spontaneous mutation rate)
      • chrom.#: 12q14.3
      • gene: type II collagen alpha 1 chain (COL2A1)
    • advanced paternal age
    • M = F

PATHOGENESIS:

1. Background

  • the Epiphyseal Dysplasias are a group of disorders characterized by flattened, fragmented, or irregular epiphyses (growth plates) and can be subdivided into those:

1. With Vertebral Involvement

  • Spondyloepiphyseal Dysplasia (SED) Congenita (SEDC)
  • SED Tarda

2. Without Verbetral Involvement

  • Multiple Epiphyseal Dysplasia
  • the gene responsible for Spondyloepiphyseal Dysplasia was identified by Lee et al., Science 244: 978 (1989) and found a 390 bp deletion is present in the COL2A1 gene which eliminates exon 48 and consequently 36 amino acids of the type II triple helical domain is lost
  • Williams et al., Hum Gen. 92(5): 499 (1993) found a single base mutation in exon 11 of the COL2A1 gene producing an Arg->Cys transition resulting in SEDC

2. Genetic Defect

  • mutation of the COL2A1 gene -> interstitial deletion -> loss of 36 amino acids in the triple helical domain of type II collagen homotrimers -> abnormal chondrogenesis -> skeletal and ocular dysplasias

CLINICAL FEATURES:

1. Musculoskeletal Manifestations

1. Limbs

  • rhizometric micromelia
  • legs - genu valgus or varum, club feet

2. Spine

  • hyperlordosis of the lumbar spine
  • dorsal kyphoscoliosis -> broad barrel chest
  • shortening of neck (with limited flexion) and trunk
  • unstable atlantoaxial joint (due to odontoid hypoplasia)
  • short stature (dwarf)

3. Others

  • head - flat face, broad nasal bridge, hypertelorism, cleft palate, highly-arched palate
  • thorax - barrel-shaped, pectus carinatum
  • pelvis - flexion contractures of the hips, hip dysplasia coxa vara, waddling gait, limp

2. Others

1. Ophthalmology

  • buphthalmos
  • cataracts
  • myopia +/- retinal detachment (50%)
  • secondary glaucoma
  • strabismus

2. Neurological

  • sensorineuronal hearing loss (recurrent otitis media)
  • infantile hypotonia
  • motor delay

INVESTIGATIONS:

1. Imaging Studies

1. Skeletal X-Rays

  • 1. Epiphyses
    • retarded ossification of epiphyseal centres especially at the ankles, knees, and hips (proximal femur)
    • eventually appear as irregular, fragmented, and flattened centres
    • vertebrae are initially ovoid but eventually become flat, irregular, narrowed and beaked with narrow disk spaces
    • hypoplastic odontoid process

    • MANAGEMENT:

    1. Supportive

    • management of complications
    • clubfeet, cleft palate, orthopedic problems, spinal column instability, eyes, motor, deformities of the legs, arthosis of hips

    2. Prognosis

    • non-lethal but lots of complications

     

     

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