CHONDRODYSPLASIA PUNCTATA (1-3)

Chondrodysplasia punctata refers to a heterogeneous group of conditions which share craniofacial dysmorphism and joint contactures and can be either rhizomelic, mesomelic or both. There is also calcific stippling of cartilage and periarticular soft tissues and, in particular, punctate calcification in the heel, in infancy. These disorders differ in clinical features, severity, inheritance pattern and radiological features, and an agreed upon classification has yet to be established.

Classification of chondrodysplasia punctata
Rhizomelic type (Autosomal recessive disorder of peroxisomal function): Congenital cataracts. Cleft palate. Small punctate calcifications in the epiphyses (knee, hip, shoulder and wrist), base of skull, posterior vertebral elements, respiratory cartilage and soft tissues. Symmetrical shortening of the femur and humerus. Short tibia and elongated fibula. Congenital hip dislocation. Flexion contractures of the extremities. Clubfeet. Micrognathia. Mental retardation and is usually lethal in infancy.	Conradi-Hünermann (non rhizomelic) type: Dominant (long arm of X-chromosome) and non lethal. This syndrome has been applied to a heterogeneous group of disorders. More widespread but milder involvement than the rhizomelic form. Scoliosis. Cataracts (in only 17% of cases as compared to 72% in the rhizomelic form). Ichthyosis (28%). Flat facies with nasal hypoplasia. Sacral ossification (sacral ossification usually begins after birth but may occasionally be seen in the third trimester). Premature calcaneal ossification (usually begins at 22-24 weeks). Cardiac lesions - the literature is not specific or consistent regarding the incidence or types of cardiac anomalies. Pulmonary arterial stenosis has been reported.
X- linked dominant type: Lethal in males. Shortening of long bones. Joint contactures. Scoliosis. Flat nasal bridge. Congenital ichthyosiform erythroderma. Alopecia of the scalp. Cataracts.	Chondrodysplasia punctata, tibial-metaphyseal type – mesomelic type. Usually survive with normal intelligence. Upper and lower limb shortening (short bowed tibia and radii, overgrowth of the fibula and ulnar hypoplasia). Stippling or deformation of the proximal humerus and femur. Punctate calcifications of the trachea, sacrum, and coronal or sagittal clefting of the vertebral bodies. Shortening of the second and third metacarpals. Patellar dislocation may be present. It may be difficult to distinguish from the rhizomelic lethal form antenatally (6) as some patients with this form also have rhizomelia (7). Flattened mid-face and nose.
X – linked recessive form: Deletion of the terminal short arm of an X chromosome (located at Xpter22.32). Nasal hypoplasia. Epiphyseal stippling. Ichthyosis. Mental retardation.
Post natal XRay

Video clip of Chondodysplasia Punctata

DIFFERENTIAL DIAGNOSIS

• Zellweger's syndrome.

REFERENCES

1. Jansen V, Sarafoglu K, Rebarber A et.al. Chondrodysplasia punctata, tibial-metaphyseal type in a 16 week fetus. J Ultrasound Med 2000;19:719-722.
2. Matsui M, Honma Y, Oguro N et.al. Case report: A newborn case of chondrodysplasia punctata, tibial-metacarpal type. Br J Radiol 1994;67:97.
3. International Working Group on Constitutional Disease of Bone: International classification of osteochondrodysplasias. Am J Med Genet 1992;44:223.
4. Bennett CP, Berry AC, Maxwell DJ, Seller MJ. Chondrodysplasia punctata: another possible X-linked recessive case.
   Am J Med Genet 1992;44:795-799.
5. Borochowitz Z. Generalized chondrodysplasia punctata with shortness of humeri and brachymetacarpy: humero-metacarpal (HM) type: variation or heterogeneity? Am J Med Genet 1991;41:417-422.
6. Argo KM, Toriello HV, Jelsema RD, Zuidema LJ.
   Prenatal findings in chondrodysplasia punctata, tibia-metacarpal type. Ultrasound Obstet Gynecol 1996;8:350-354.
7. Rittler M, Menger H, and Spranger J. Chondrodysplasia punctate, tibia-metacarpal (MT) type. Am J Med Genet 1990;37:200-208.
8. Braverman N, Steel G, Obie C, Moser A, Moser H, Gould SJ, Valle D.
   Human PEX7 encodes the peroxisomal PTS2 receptor and is responsible for rhizomelic chondrodysplasia punctata.
   Nat Genet 1997;15:369-376.
9. Bruch D, Megahed M, Majewski F, Ruzicka T.
   Ichthyotic and psoriasiform skin lesions along Blaschko's lines in a woman with X-linked dominant chondrodysplasia punctata.
   J Am Acad Dermatol 1995;33:356-360.
10. Fourie DT. Chondrodysplasia punctata: case report and literature review of patients with heart lesions.
    Pediatr Cardiol 1995;16:247-250.
    Fryburg JS, Kelly TE. Chondrodysplasia punctata, humero-metacarpal type: a second case. Am J Med Genet 1996;64:493-496
11. Gobello T, Mazzanti C, Fileccia P, Didona B, Papi M, Atzori F, Cavalieri R. X-linked dominant chondrodysplasia punctata (Happle syndrome) with uncommon symmetrical shortening of the tubular bones.
    Dermatology 1995;191:323-327.
12. Gobello T, Mazzanti C, Fileccia P, Didona B, Papi M, Atzori F, Cavalieri R.
    X-linked dominant chondrodysplasia punctata (Happle syndrome) with uncommon symmetrical shortening of the tubular bones.
    Dermatology 1995;191:323-327.
13. Gobello T, Mazzanti C, Fileccia P, Didona B, Papi M, Atzori F, Cavalieri R.
    X-linked dominant chondrodysplasia punctata (Happle syndrome) with uncommon symmetrical shortening of the tubular bones.
    Dermatology 1995;191:323-327.