2005-02-21-11 Trisomy 13 © Hernandez www.thefetus.net/
Alberto Hernandez-Campos, MD
Guadalajara, Jalisco MEXICO
Synonyms: Trisomy 13, Bartholin-Patau Syndrome, Trisomy D1
Definition: Trisomy 13 refers to an extra copy of chromosome 13 which is a medium-length acrocentric chromosome.
Case report: We present a case of a 26 year-old primigravida. Her husband had a previous son from a previous marriage. That first son presented several physical anomalies at birth, including cleft lip, increased head size, cardiac anomalies, and supernumerary fingers in one hand. That baby died soon after a couple of hours birth. The current pregnancy is a dichorionic diamniotic twin pregnancy. The first twin (male) was normal.
The second twin (male) had with mild unilateral hydrocephalus, cleft lip (not shown), absent nasal bone, dextrocardia, ventricular septal defect, single umbilical artery (right artery absent) and hyperflexion of the right hand. Because of this, an amniocentesis with karyotype was performed of the affected fetus, which resulted in 47, XY +13. Both babies were delivered at term, but the affected fetus died next day. The other baby was entirely normal. The father refused karyotype even when he was suspected to carry a Robertsonian translocation.
Single umbilical artery, right umbilical artery is absent:
Umbilical vein, aorta and pulmonary artery:
Ventricular septal defect and pseudo-overriding of aorta:
Normal circle of Willis:
Absent nasal bone:
Hyperflexion of hand:
History: This condition was first identified as a cytogenetic syndrome in 1960 by Patau et al.
Prevalence: The prevalence of the syndrome is approximately 1-2:10,000. The risk of having a child with trisomy 13 increases with maternal age as other trisomies. The sex ratio at birth is skewed toward females, presumably because of decreased survival among males, with continued skewing of the ratio further toward females as these children age (Best, 2002). It is the third most frequent trisomy among live births (Jones, 1998). It is the most severe of the viable autosomal trisomies.
Etiology: Trisomy 13 is caused by the presence of an extra copy of chromosome 13 and is considered an autosomic trisomy. Mosaicism for chromosome 13 is also implicated in etiology as well as Robertsonian translocation with an extra copy of chromosome 13 attached to another acrocentric chromosome (e.g. 13-15, 21, 22). Aneuploidy is most often the result of nondisjuntion during maternal meiosis 1.
Pathogenesis: While the exact mechanisms by which chromosomal trisomies disrupt development are unknown, considerable attention has been paid to trisomy 21 as a model system for the autosomal trisomies. Normal development requires 2 (and only 2) copies of most of the human autosomal genome; the presence of a third copy of an autosome generally is lethal to the developing embryo. Therefore, trisomy 13 is distinctive in that it is 1 of only 3 autosomal trisomies for which development can proceed to live birth. In fact, trisomy 13 is the largest autosomal imbalance that can be sustained by the embryo and yet allow survival to term. Complex physiologic structures, such as those found in the CNS and heart, appear to be particularly sensitive to chromosomal imbalance, either through the actions of individual genes or by the destabilization of developmental processes involving many genes in concert. The sex ratio at birth is skewed toward females, presumably because of decreased survival among males, with continued skewing of the ratio further toward females as these children age. Trisomy 13 is expressed prenatally and is fully evident at birth. Significant numbers of cases that are trisomic for chromosome 13 end in spontaneous abortion, fetal demise, or stillbirth. The mortality rate is very high among neonates. Children who survive the neonatal period continue to express developmental delays and to exhibit a declining developmental quotient over time. This decline does not result from loss of developmental milestones but instead reflects a worsening developmental lag compared to other children.
Sonographic findings: Holoprosencephaly, hydrocephalus, microcephaly, arhinencephaly, anophthalmia, micrognathia, small or absent nasal bone, cleft lip and palate, hypertelorism, low-set ears, cardiomegaly, dextrocardia, atrial septal defect, ventricular septal defect, severe fetal bradycardia, post-axial polydactyly, flexion of the fingers (different form that of trisomy 18), rocker bottom feet, intrauterine growth retardation, oligo-anhydramnios, polycystic kidneys, hydronephrosis, neural tube defects.
Implications for targeted examinations: Look for holoprosencephaly and cardiac or renal anomalies. This trisomy is also characterized by the following triad: microphthalmia, cleft lip and palate and polydactyly.
Differential diagnosis: Smith-Lemli-Opitz syndrome, trisomy 18, partial duplication of 13q.
Associated anomalies: Capillary hemangiomata, deep palmar creases in the hand, prominent glabellae, pseudostrabismus, convex soles, syndactyly, pseudostrabismus, aplasia cutis, omphalocele, hernias, patent ductus arteriosus, coloboma, retinal dysplasia, cryptorchidism, microphthalmia.
Prenatal Diagnosis: Chorionic villous sampling and amniocentesis with conventional karyotype are required for diagnosis. If fluorescent in situ hybridization (FISH) on interphase cells is used to obtain a rapid diagnosis, confirm results with conventional cytogenetic methods. Do not make irreversible pregnancy management decisions based solely on FISH results. Multiple marker screening (e.g., maternal serum alpha-fetoprotein [MSAFP], human chorionic gonadotropin [hCG], unconjugated estriol) is not usually sensitive to the presence of trisomy 13 . Mosaicism for trisomy 13 is associated with a milder degree of severity, with the mildest expression typically in the lowest levels of mosaicism. Higher levels of mosaicism are associated more closely to full constitutional trisomy. Because of the possibility of different levels of mosaicism in different tissues, no level of mosaicism can be presumed benign.
Prognosis: Median survival age for children with trisomy 13 is 2.5 days, with only 1 child in 20 surviving longer than 6 months. However, some children survive into their teens and seem to fare better than might be expected based on reports from those who die in the perinatal period. Reports of adults with trisomy 13 are rare. Holoprosencephaly, a frequent brain malformation associated with trisomy 13 , is associated with severe neurological impairment, and development of the structural features of the mid face is disrupted when holoprosencephaly is present. Serious cardiac anomalies are often present. Most common causes of death are cardiopulmonary arrest, 69%; congenital heart disease, 13%; and pneumonia, 4%. Survivors with trisomy 13 exhibit severe mental retardation and developmental delays and are at increased risk for malignancy. Infants who survive the neonatal period have an average length of stay in a neonatal ICU of 10.8 days.
Recurrence risk: Recurrence risks differ based on the details of the chromosome abnormality and the mother"s age. In general, for freestanding trisomy 13, the recurrence risk for trisomy 13 or another clinically viable trisomy (i.e., trisomy 21, trisomy 18) is approximately 0.5% above the mother"s age-related risk for autosomal trisomies. Mosaic trisomy 13 is also not inherited. It occurs as a random error during cell division early in fetal development. As a result, some of the body"s cells have the usual two copies of chromosome 13, and other cells have three copies of the chromosome. Trisomy 13 due to a translocation can be inherited. An unaffected person can carry a rearrangement of genetic material between chromosome 13 and another chromosome. This rearrangement is called a balanced translocation because there is no extra material from chromosome 13. Although they do not have signs of trisomy 13 , people who carry this type of balanced translocation are at an increased risk of having children with the condition. Recurrence risks for Robertsonian and other structural rearrangements vary considerably; these risks can be as high as 100% in rare cases in which a parental translocation occurs involving both copies of chromosome 13. Perform parental blood chromosome studies in the event that a Robertsonian translocation or other structural chromosome abnormality is found because as you see, recurrence risks may be markedly different for freestanding trisomy versus structural rearrangements.
Management: Termination of pregnancy is an option for the patient with a fetus exhibiting trisomy 13 before 24 weeks of gestation. If trisomy 13 is discovered in the prenatal period after 24 weeks of gestation or if the patient elects to continue the pregnancy diagnosed at an earlier gestational age, counseling that discusses the utility of performing a cesarean delivery for fetal indications is appropriate. Avoid exposing a pregnant woman to the risks of a major operation with little expected benefit to the neonate. Provide surviving children with trisomy 13 the same care other children receive, including visual assessments, audio evaluations by age 6-8 months, and immunizations. Treat health problems according to severity and always in the best interests of the child. Babies with trisomy 13 are notably irritable, showing muscular myotonia or hypotonia. Older children are at risk of developing scoliosis. Prior to dental procedures, administer prophylactic antibiotics for children with cardiac anomalies. Surgical interventions are generally withheld for the first few months of life because of the high mortality rates of babies with trisomy 13. Carefully weigh decisions about extraordinary life-prolonging measures against the severity of the neurological and physical defects that are present and the likelihood of postsurgical recovery or prolonged survival. Although those who survive trisomy 13 have low educational potential in which case, increased stimulation and interaction are appropriate to maximize developmental potential. Specific growth charts are available for monitoring growth of children with trisomy 13. Continue monitoring for apneic episodes.
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