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Patau Syndrome | Autosomal Trisomies | USMLE step 1 | Lecture 13

Trisomy 13 syndrome — Trisomy 13 syndrome is a severe chromosomal disorder caused by an extra copy of chromosome 13. The three etiologies of trisomy 13 (also called Patau syndrome) are: ●Trisomy 13 (47,+13), with three copies of chromosome 13 in each cell of the body as a result of meiotic error. This form is associated with advanced maternal age. ●Unbalanced Robertsonian translocation, with two normal copies of chromosome 13 and an extra copy of the long arm of chromosome 13 translocated to one of the other acrocentric chromosomes (ie, 14, 15, 21, 22) resulting in full trisomy 13. This type of trisomy 13 is not related to advanced maternal age. Although a balanced Robertsonian translocation involving chromosome 13 and 14 (ie, 45,t(13;14)(q10;q10)) is relatively common, there is a low risk for the carrier to bear offspring with an unbalanced chromosome complement because the high rate (98 to 99 percent) of early embryonic death. ●Trisomy 13 mosaicism (47,+13/46), with three copies of chromosome 13 in some cells and two copies in others. This form is caused by a mitotic nondisjunction error and is not related to maternal age. Trisomy 13 syndrome is characterized by severe, multiple congenital anomalies. The classic triad is micro/anophthalmia, cleft lip and/or palate, and postaxial polydactyly, but the clinical presentation in patients with trisomy 13 can be quite variable. Abnormalities observed in more than or equal to 50 percent of trisomy 13 patients include: ●Central nervous system (CNS) – Holoprosencephaly with incomplete development of forebrain and olfactory and optic nerves, severe intellectual disability, deafness ●Craniofacial – Abnormal auricles, microphthalmia/anophthalmia, colobomata, sloping forehead (fissure or cleft of the iris, ciliary body, or choroid) ●Skin and limbs – Capillary hemangiomata, simian crease, hyperconvex narrow fingernails, polydactyly of hands and sometimes feet, prominent heel ●Cardiac – Found in approximately 80 percent of patients; includes ventricular septal defect (VSD), patent ductus arteriosus (PDA), atrial septal defect (ASD), and dextroposition ●Genitalia – Cryptorchidism in males; bicornuate uterus in females Other abnormalities observed in less than 50 percent of patients include [54,55]: ●Growth – Prenatal growth deficiency ●CNS – Hyper- or hypotonia, agenesis of corpus callosum, cerebral hypoplasia ●Eyes – Hypo- or hypertelorism, cyclopia, upslanting palpebral fissures ●Nose, mouth, mandible – Absent philtrum, narrow palate, micrognathia ●Hands and feet – Retroflexible thumb, syndactyly, cleft between first and second toes, hypoplastic toenails, radial aplasia ●Abdomen – Omphalocele, incomplete rotation of colon, Meckel diverticulum ●Renal – Polycystic kidney, hydronephrosis, horseshoe kidney Prenatal sonographic findings of the characteristic CNS defects are the most common fetal signs suggestive of this diagnosis. The prevalence of trisomy 13 in newborns is 1 in 5000. The majority of prenatally diagnosed cases of trisomy 13 die in utero. The median survival for liveborn children is seven days, and 91 percent die within the first year, with the majority (approximately 80 percent) dying within the first month of life. There are several published cases of patients with trisomy 13 who are over five years of age. Cardiac anomalies were reported in only 46 percent of the long-lived survivors, in contrast to the much higher frequency (up to 80 percent) reported in all trisomy 13 cases. This finding suggests that the lower frequency of heart defects may contribute to the longer survival. Intensive treatments, including resuscitation and surgical procedures, may prolong survival. As an example, a retrospective study from 1989 to 2010 that included 16 Japanese patients with trisomy 13 who had received intensive treatment showed a median survival time of 24 months. Severe intellectual disability, seizures, and failure to thrive are common in survivors over one year of age. As with trisomy 18, a "noninterventional paradigm" of providing supportive, but not intensive, treatment has been recommended for trisomy 13 because of the high mortality of the disorder, the severe intellectual disability in those that survive beyond one year of age, and the lack of a cure. However, acceptance of this paradigm is not universal, because survival beyond infancy is possible, particularly in those who receive intensive treatment. In a Canadian cohort of 174 children with trisomy 13, mean 1-year survival was 19.8 percent, and 10-year survival was 12.9 percent. Most deaths occurred in the first three months of life. Twenty-nine of the 41 children who underwent surgeries ranging from simple interventions such as myringotomy to complex cardiac repairs survived for at least one year after the first surgery. Options for management of trisomy 13 are similar to that for trisomy 18.