Скачать с ютуб Trisomy 8 and 9 syndrome | Autosomal Trisomies | USMLE step 1|Lecture 14 в хорошем качестве

Trisomy 8 and 9 syndrome | Autosomal Trisomies | USMLE step 1|Lecture 14

Trisomy 8 syndrome — Full trisomy 8 is estimated to occur in 0.1 percent of all clinically recognized pregnancies and is usually lethal. In liveborn infants, trisomy 8 is almost always a mosaic (47,+8/46). The estimated frequency of mosaic trisomy 8 in liveborn infants is 1 in 25,000 to 1 in 50,000. A skewed sex ratio (3:1 male: female) is observed in mosaic cases. If the prenatal testing was performed on a chorionic villus sample (CVS), one should keep in mind that the incidence of confined placental mosaicism is high, and oftentimes the fetus is not affected. In these cases, a follow-up amniocentesis is recommended. Ultrasonographic detection of agenesis of the corpus callosum and ventriculomegaly should alert to the possibility of mosaic trisomy 8. In addition, mosaic trisomy 8 is sometimes associated with an elevated maternal serum alpha-fetoprotein. A diagnosis of mosaic trisomy 8 can be difficult to establish and can be missed at amniocentesis. A normal chromosome constitution in lymphocyte culture does not exclude trisomy 8 mosaicism, since abnormal cell lines are far more likely to be detected in fibroblast cultures (eg, skin biopsy, or other tissues) than in lymphocytes, making the condition difficult to diagnose. Trisomy 8 mosaicism is also difficult to diagnose postnatally due to great phenotypic variation. The severity of the phenotype does not appear to correlate with the level (ie, percentage) and distribution of the trisomic cells in tissue types. Characteristic phenotypic features include agenesis of the corpus callosum, ventriculomegaly, skeletal and joint abnormalities, congenital heart defects, deep palmar and plantar creases, facial dysmorphism, and moderate to severe intellectual disability. The growth of children with trisomy 8 is variable, ranging from small to tall stature. Life expectancy is usually normal. Molecular studies revealed that trisomy 8 mosaicism in live-borns almost always originates from postzygotic mitotic error. Parental ages of liveborn infants with trisomy 8 mosaicism are usually not increased, and cases with uniparental disomy (UPD) 8 are rare because they can only originate from a meiotic nondisjunction error. Genetic counseling is difficult due to great phenotypic variability. Prognosis, management, and treatment depend upon the specific clinical abnormalities in the patient (eg, repair of cleft palate or heart defects, surgical intervention for hydronephrosis). Patients and families should be made aware of a possible association with malignancy. Early assessment for intellectual disability is recommended for additional assistance in providing special education programs. Trisomy 9 syndrome — Full trisomy 9 occurs in approximately 0.1 percent of conceptions and is almost always lethal. The phenotype appears to be similar in the several liveborn infants described so far and consists of severe growth restriction, characteristic facial appearance (eg, micrognathia, bulbous nose, low-set ears), cleft palate, skeletal abnormalities (eg, dislocated joins), heart abnormalities (eg, ventricular septal defect), hypoplastic genitalia, and renal and brain abnormalities. The survival time after birth varies between minutes to nine months. The majority of liveborn individuals with trisomy 9 have a mosaic karyotype (47,+9/46) that may be detected in amniocytes or a peripheral blood sample. Mosaic trisomy 9 observed in a CVS specimen should be interpreted with caution due the possibility of mosaicism confined to the placenta. The constellation of phenotypic abnormalities of trisomy 9 mosaicism is similar to that seen in liveborn infants with full trisomy 9 described above. Failure to thrive, severe intellectual and motor deficiency, cryptorchidism in males, and renal cysts are common. Death typically occurs at less than 1 year of age, although longer survival intervals have been reported. Based upon molecular studies, it appears that trisomy 9 is caused by a meiotic error, and subsequent trisomy rescue leads to mosaicism in surviving embryos. In some cases, UPD has been documented in the diploid cell line. Association with advanced maternal age is observed, similar to other trisomy syndromes. The percentage of mosaicism appears not to correlate with clinical manifestations and does not help to predict survival. Medical intervention depends upon the presence and severity of abnormalities. Genetic counseling and early assessment are recommended to provide any necessary special medical/educational assistance.