See Molecular Genetics for information on allelic variants detected in this gene. Sequence analysis detects variants that are benign, likely benign, of uncertain significance , likely pathogenic, or pathogenic. For issues to consider in interpretation of sequence analysis results, click here. Review of approximately 80 pathogenic variants in all available published case literature, ClinVar [ Landrum et al ], and HGMD [ Stenson et al ] did not identify large intragenic deletions or duplications as a cause of CDPX2 [Author, personal observation]. Methods used may include quantitative PCR , long-range PCR, multiplex ligation-dependent probe amplification MLPA , and a gene -targeted microarray designed to detect single- exon deletions or duplications.
|Published (Last):||25 August 2007|
|PDF File Size:||1.34 Mb|
|ePub File Size:||4.93 Mb|
|Price:||Free* [*Free Regsitration Required]|
See Molecular Genetics for information on allelic variants detected in this gene. Sequence analysis detects variants that are benign, likely benign, of uncertain significance , likely pathogenic, or pathogenic. For issues to consider in interpretation of sequence analysis results, click here. Review of approximately 80 pathogenic variants in all available published case literature, ClinVar [ Landrum et al ], and HGMD [ Stenson et al ] did not identify large intragenic deletions or duplications as a cause of CDPX2 [Author, personal observation].
Methods used may include quantitative PCR , long-range PCR, multiplex ligation-dependent probe amplification MLPA , and a gene -targeted microarray designed to detect single- exon deletions or duplications. Clinical Characteristics Clinical Description Variability in females. The clinical phenotypes in heterozygous females are highly variable and depend on the pattern of X-chromosome inactivation in relevant tissues i. Phenotypes range from fetal demise with multiple malformations and severe growth retardation to much milder manifestations, such as adults with only cutaneous features, short stature, or no recognizable physical abnormalities.
Severity in females varies greatly within families and among individuals with the same pathogenic variant, as would be expected for a pathogenic process determined, in part, by the random process of X-chromosome inactivation.
Phenotypes in males. Although CDPX2 was for many years presumed to be lethal in males, a small number of affected males have been reported. The clinical characteristics of males with mosaic EBP pathogenic variants are well within the marked variability described in affected females. Reported heights range from the 10thth percentile to 6 SD below the mean. Craniofacial appearance. The face and head are often asymmetric. Most individuals with CDPX2 have a depressed bridge and frontal bossing. Other distinctive features include downslanting palpebral fissures, hypertelorism, low-set ears, and high-arched palate [ Happle , Herman ].
Epiphyseal stippling can be detected on prenatal ultrasound from the second trimester [ Lefebvre et al ] and is present in infancy and variably in childhood during endochondral bone formation. It is usually radiologically absent in adults with CDPX2.
Moderate-to-severe kyphoscoliosis is common and can present in infancy or early childhood. Lung disease may develop secondary to progressive kyphoscoliosis and can lead to death [ Sutphen et al ].
Spinal deformities can progress rapidly; in addition, progressive deformity following surgical vertebral fusion is common [ Mason et al ]. Skin, hair, and nails. Scaling ichthyosis on an erythematous base is present in newborns in a linear or blotchy pattern. The ichthyosis follows the lines of Blaschko and has a feather-like edge, but total scaling erythroderma also occurs.
As the rash fades in the first weeks or months of life, it leaves a linear or whorled pattern of atrophoderma predominantly near hair follicles where scales had been located.
Hair findings include scarring alopecia in patches, sparse eyelashes and eyebrows, and coarse, lusterless hair. Minor nail findings include flattening and splitting of the nail plates [ Happle , Herman , Hoang et al ]. Approximately two thirds of individuals have cataracts at birth or develop them early in life. Intelligence is typically normal in affected individuals unless a CNS malformation is present.
Rarely reported neurologic abnormalities in males include posterior fossa arachnoid cysts and medullary atrophy secondary to atlas hypoplasia [ Horinouchi et al ]. Ear anomalies and hearing. Rarely, dysplastic auricles and sensorineural hearing loss have been reported in affected individuals [ Happle , Herman et al , Ozyurt et al ]. Other findings.
Listen Making a diagnosis for a genetic or rare disease can often be challenging. The following resources provide information relating to diagnosis and testing for this condition. If you have questions about getting a diagnosis, you should contact a healthcare professional. The intended audience for the GTR is health care providers and researchers. Patients and consumers with specific questions about a genetic test should contact a health care provider or a genetics professional. Listen If you need medical advice, you can look for doctors or other healthcare professionals who have experience with this disease.
Condrodisplasia punctata rizomélica
Description Rhizomelic chondrodysplasia punctata is a condition that impairs the normal development of many parts of the body. The major features of this disorder include skeletal abnormalities, distinctive facial features, intellectual disability, and respiratory problems. Rhizomelic chondrodysplasia punctata is characterized by shortening of the bones in the upper arms and thighs rhizomelia. Affected individuals also have a specific bone abnormality called chondrodysplasia punctata, which affects the growth of the long bones and can be seen on x-rays. People with rhizomelic chondrodysplasia punctata often develop joint deformities contractures that make the joints stiff and painful. Distinctive facial features are also seen with rhizomelic chondrodysplasia punctata. These include a prominent forehead , widely set eyes hypertelorism , a sunken appearance of the middle of the face midface hypoplasia , a small nose with upturned nostrils, and full cheeks.
Rhizomelic chondrodysplasia punctata type 1