= CONGENITAL STIPPLED EPIPHYSES = DYSPLASIA EPIPHYSEALIS PUNCTATA = CHONDRODYSTROPHIA CALCIFICANS CONGENITA

= group of syndromes characterized by abnormal calcific foci in areas of enchondral bone formation

Etiology: peroxisomal disorder characterized by fibroblast plasmalogen deficiency

Prevalence: 1÷110,000 births

Genetics: X-linked autosomal

• recessive = alterations in peroxisomal metabolism
• dominant = mutations in delta 8 sterol isomerase enzyme → abnormal cholesterol biosynthesis (cholesterol is essential to proper function of Sonic hedgehog class of embryonic signaling proteins)

Associated with: congenital ichthyosiform erythroderma = generalized erythema with characteristic feathery adherent hyperkeratotic scale

Radiograph:

• calcific stippling of epiphyses (prior to normal epiphyseal ossification)
• scoliosis, kyphosis

1. Autosomal Recessive Chondrodysplasia Punctata
   = RHIZOMELIC TYPE
   Associated with: CHD (common)
   • craniofacial dysmorphism = flat face with small saddle nose
   • congenital cataracts
   • severe mental retardation, spastic tetraplegia
   • thermoregulatory instability
   • cleft palate
   • multiple small punctate calcifications of varying size in epiphyses (knee, hip, shoulder, wrist), base of skull, posterior elements of vertebrae, respiratory cartilage and soft tissues (neck, rib ends) before appearance of ossification centers
   • prominent symmetrical shortening of femur + humerus (rarely all limbs symmetrically affected)
   • congenital dislocation of hip
   • multiple flexion (joint) contractures of extremities
   • clubfeet
   • metaphyseal splaying of proximal tubular bones (in particular about knee)
   • thickening of diaphyses
   • prominent vertebral + paravertebral calcifications
   • coronal clefts in vertebral bodies
   
   OB-US:
   • ascites, polyhydramnios
   
   Prognosis: death usually <1 year of age
   DDx: Zellweger syndrome
2. Conradi-Hünermann-Happle Syndrome
   = NONRHIZOMELIC TYPE
   more common milder nonlethal variety
   Genetics: mutation localized to Xp11.23 to EBP gene
   • normal intelligence
   • more widespread but milder involvement as above
     Prognosis: survival often into adulthood
   
   Cx: respiratory failure (severe underdevelopment of ribs), tracheal stenosis, spinal cord compression
   DDx:
   1. Cretinism (may show epiphyseal fragmentation, much larger calcifications within epiphysis)
   2. Warfarin embryopathy
   3. Zellweger syndrome