IllnessChondrodysplasia punctata, differential diagnosis

NGS +

[Sanger]

All forms of chondrodysplasia punctata (CP) impair cartilage and bone development and show up as "stippling" on radiographs. In X-linked CP (XLCP) 1, the stippling generally disappears in early childhood. Characteristic features include short stature, unusually short fingertips and toes, and prominent facial features. Patients, usually male, are usually of normal intelligence and have normal life expectancy. Some affected individuals develop serious complications such as airway obstruction, spinal cord compression, developmental delay, hearing loss, visual disturbances, and heart defects. XLCP 2 is characterized by skin and eye abnormalities in addition to bone damage. Symptoms vary widely, but mottling disappears in early childhood. Other skeletal abnormalities include asymmetric rhizomelia and progressive kyphoscoliosis with short stature. Neonates have ichthyosis, later follicular atrophoderma with sparse, coarse scalp hair, and congenital or early cataract, microphthalmia, and microcornea. In the female Gsex, XLCP 2 is usually associated with normal intelligence and life expectancy. A much more severe form occurs in very few boys; it is associated with various birth defects, hypotonia, severe developmental delay and seizures. In rhizomelic CP (RCP), the normal development is impaired with skeletal abnormalities, mental retardation, respiratory problems, contractures and congenital or early cataracts. Affected infants grow very slowly, many have seizures. Recurrent respiratory infections and severe respiratory problems are common. As a result, most patients survive only into infancy. Three RCP subtypes with similar features are distinguished by mutations in the PEX7, GNPAT and AGPS genes, while XLCP 1 and 2 are caused by ARSL and EBP mutations, respectively. A negative DNA test result cannot exclude the clinical diagnosis with certainty.

References: https://www.ncbi.nlm.nih.gov/books/NBK1544/

https://www.ncbi.nlm.nih.gov/books/NBK55062/

https://www.ncbi.nlm.nih.gov/books/NBK1270/

• Alias: Arylsulfatase E Deficiency (CDPX1)
• Alias: Brachytelephalangic chondrodysplasia punctata, BCDP
• Alias: Chondrodysplasia punctata 1, XL (ARSL)
• Alias: Chondrodysplasia punctata 2, XL (EBP)
• Alias: Chondrodysplasia punctata, CDP
• Alias: Chondrodysplasia punctata, rhizomelic (PEX7, GNPAT, AGPS)
• Alias: Chondrodysplasie p.
• Alias: Conradi-Hünermann[-Happle] syndrome (EBP)
• Alias: Happle syndrome (EBP)
• Alias: XLR chondrodysplasia punctata 1 (ARSL)
• Allelic: Cataracts, spastic paraparesis + speech delay (FAR1)
• Allelic: Pelger-Huet anomaly (LBR)
• Allelic: Peroxisome biogenesis disorder 2A, Zellweger (PEX5)
• Allelic: Peroxisome biogenesis disorder 2B (PEX5)
• Allelic: Reynolds syndrome (LBR)
• Antley-Bixler syndrome with genital anomalies + disordered steroidogenesis (POR)
• CK syndrome: Mental retardation, XL, thin habitus, cortical malformation (NSDHL)
• Chondrodysplasia punctata, XLD (EBP)
• Chondrodysplasia punctata, rhizomelic, type 2 (GNPAT)
• Congenital hemidysplasia, ichthyosis, limb defects (CHILD) syndrome (NSDHL)
• Conradi-Hünermann syndrome, Happle syndrome (EBP)
• Desmosterolosis (DHCR25)
• Disordered steroidogenesis due to cytochrome P450 oxidoreductase (POR)
• Greenberg skeletal dysplasia (LBR)
• Keutel syndrome: Pulm. stenoses, brachytelephalangy, deafness, abnormal cartilage ossification (MGP)
• Lathosterolosis (SC5D)
• Lipodystrophy, congenital generalized, type 1 (AGPS)
• Male EBP disorder with neurologic defects [MEND] syndrome (EBP)
• Microcephaly, congenital cataract + psoriasiform dermatitis (MSMO1)
• Pelger-Huet anomaly with mild skeletal anomalies (LBR)
• Peroxisomal fatty acyl-CoA reductase 1 disorder (FAR1)
• Pseudoxanthoma elasticum-like disorder with multiple coagulation factor deficiency (GGCX)
• Pulmonic stenoses, brachytelephalangy, deaf, abnormal cartilage ossification/calcification (MGP)
• Refsum peroxisomal disease 9B (PEX7)
• Rhizomelic chondrodysplasia punctata, type 1 (PEX7)
• Rhizomelic chondrodysplasia punctata, type 2 (GNPAT)
• Rhizomelic chondrodysplasia punctata, type 3 (AGPS)
• Rhizomelic chondrodysplasia punctata, type 4 (FAR1)
• Rhizomelic chondrodysplasia punctata, type 5 (PEX5)
• Ritscher-Schinzel syndrome 3 (VPS35L)
• Vitamin K-dependent clotting factors, combined deficiency of, 1 (GGCX)
• XLD chondrodysplasia punctata as phenocopy of warfarin embryopathy (VKORC1)