Patau Syndrome

Author: Robert G Best, PhD, FACMG; Chief Editor: Bruce Buehler, MD more...

Updated: Nov 10, 2009

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Background
Pathophysiology
Epidemiology
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Background

Patau syndrome is the least common and most severe of the viable autosomal trisomies. Median survival is fewer than 3 days. First identified as a cytogenetic syndrome in 1960, Patau syndrome is caused by an extra copy of chromosome 13, a medium-length acrocentric chromosome.

Chromosome 13.

Many of the clinical features widely vary; however, severe mental deficiency is a consistent feature in children born with Patau syndrome. Holoprosencephaly, polydactyly, flexion of the fingers, rocker-bottom feet, facial clefting, neural tube defects, and heart defects are also frequent clinical features. Patau syndrome is generally recognized at birth by the presence of structural birth defects and poor neurologic performance.

Pathophysiology

Patau syndrome is caused by the presence of an extra copy of chromosome 13, generally present at conception and transmitted to every cell in the body. Although 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 is generally lethal to the developing embryo. Therefore, trisomy 13 is distinctive in that it is one 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.

Frequency

United States

Incidence of Patau syndrome is approximately 1 case per 8,000-12,000 live births. Significant racial or geographic differences in frequency are not evident, although a well-known association is recognized between Patau syndrome and increased maternal age, an association common to all autosomal trisomies in fetuses that survive to term.

Mortality/Morbidity

Median survival age for children with Patau syndrome is 2.5 days, with only one in 20 children 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 Patau syndrome are rare.

Holoprosencephaly, a frequent brain malformation associated with Patau syndrome, is associated with severe neurological impairment; 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%),^[1]congenital heart disease (13%), and pneumonia (4%). Survivors with Patau syndrome 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.

Sex

The sex ratio at birth is slightly skewed toward females, presumably because of decreased survival among males, with continued skewing of the ratio further toward females as these children age.

Age

Patau syndrome is expressed prenatally and is fully evident at birth. A significant number of cases that are trisomic for chromosome 13 end in spontaneous abortion, fetal demise, or stillbirth.^[2]The mortality rate is very high among neonates. Children who survive the neonatal period continue to express developmental delays and 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 with other children. A report on a group of 21 individuals with Patau syndrome (3 mosaic and 18 nonmosaic) who survived past age 5 years showed the oldest to be aged 21 years.

Proceed to Clinical Presentation

Contributor Information and Disclosures

Author

Robert G Best, PhD, FACMG Professor and Director, Division of Clinical Genetics and Molecular Medicine, University of South Carolina School of Medicine

Robert G Best, PhD, FACMG is a member of the following medical societies: American Academy of Nanomedicine, American College of Medical Genetics, and American Society of Human Genetics

Disclosure: Nothing to disclose.

Coauthor(s)

Anthony Romaine Gregg, MD Associate Professor, Director, Division of Maternal and Fetal Medicine, Medical Director, Division of Genetics, Medical Director, Genetics Counseling Program, Department of Obstetrics and Gynecology, University of South Carolina School of Medicine

Anthony Romaine Gregg, MD is a member of the following medical societies: American Association for the Advancement of Science, American College of Medical Genetics, American College of Obstetricians and Gynecologists, American Institute of Ultrasound in Medicine, American Medical Association, American Society of Human Genetics, Central Association of Obstetricians and Gynecologists, Perinatal Research Society, Society for Gynecologic Investigation, Society for Maternal-Fetal Medicine, and Society for the Study of Reproduction

Disclosure: Nothing to disclose.

Specialty Editor Board

Elaine H Zackai, MD Professor of Pediatrics, Professor of Obstetrics and Gynecology, Professor of Pediatrics in Human Genetics, University of Pennsylvania School of Medicine; Director, Clinical Genetics Center, University of Pennsylvania; Senior Physician and Director of Clinical Genetics, The Children's Hospital of Philadelphia

Elaine H Zackai, MD is a member of the following medical societies: American Cleft Palate/Craniofacial Association, American College of Medical Genetics, and American Society of Human Genetics

Disclosure: Nothing to disclose.

Mary L Windle, PharmD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy, Pharmacy Editor, eMedicine

Disclosure: Pfizer Inc Stock Investment from financial planner; Avanir Pharma Stock Investment from financial planner ; WebMD Salary and stock Employment and investment from financial planner

Robert Anthony Saul, MD Clinical Professor, Department of Pediatrics, University of South Carolina; Senior Clinical Geneticist, Greenwood Genetic Center

Robert Anthony Saul, MD is a member of the following medical societies: American Academy of Pediatrics, American College of Medical Genetics, and American College of Physician Executives

Disclosure: Nothing to disclose.

Daniel Rauch, MD, FAAP Director, Pediatric Hospitalist Program, Associate Professor, Department of Pediatrics, New York University School of Medicine

Daniel Rauch, MD, FAAP is a member of the following medical societies: Ambulatory Pediatric Association, American Academy of Pediatrics, and Society of Hospital Medicine

Disclosure: Baxter Honoraria Consulting

Chief Editor

Bruce Buehler, MD Professor, Department of Pediatrics, Pathology and Microbiology, Executive Director, Hattie B Munroe Center for Human Genetics, University of Nebraska Medical Center

Bruce Buehler, MD is a member of the following medical societies: American Academy for Cerebral Palsy and Developmental Medicine, American Academy of Pediatrics, American Association on Mental Retardation, American College of Medical Genetics, American College of Physician Executives, American Medical Association, and Nebraska Medical Association

Disclosure: Nothing to disclose.

References

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Morris JK, Savva GM. The risk of fetal loss following a prenatal diagnosis of trisomy 13 or trisomy 18. Am J Med Genet A. Apr 1 2008;146(7):827-32. [Medline].
[Guideline] American College of Obstetricians and Gynecologists (ACOG). Screening for fetal chromosomal abnormalities. Washington (DC): American College of Obstetricians and Gynecologists (ACOG); 2007 Jan. 11 p. (ACOG practice bulletin; no. 77). [Full Text].
Barnes AM. Care of the Infant and Child With Trisomy 18 or 13: Medical Problems, Reported treatments and Milestones. 2^nd ed. University of Nebraska Medical Center; 2000.
Baty BJ, Blackburn BL, Carey JC. Natural history of trisomy 18 and trisomy 13: I. Growth, physical assessment, medical histories, survival, and recurrence risk. Am J Med Genet. Jan 15 1994;49(2):175-88. [Medline].
Fogu G, Maserati E, Cambosu F, Moro MA, Poddie F, Soro G, et al. Patau syndrome with long survival in a case of unusual mosaic trisomy 13. Eur J Med Genet. Jul-Aug 2008;51(4):303-14. [Medline].
Goldstein H, Nielsen KG. Rates and survival of individuals with trisomy 13 and 18. Data from a 10-year period in Denmark. Clinical Genetics. Dec 1988;34(6):366-72. [Medline].
Iliopoulos D, Sekerli E, Vassiliou G, et al. Patau syndrome with a long survival (146 months): a clinical report and review of literature. Am J Med Genet A. Jan 1 2006;140(1):92-3. [Medline].
Jones KL. Trisomy 13 syndrome. In: Smith's Recognizable Patterns of Human Malformation. 5th Edition. Saunders/Elsevier; 1997:18-23.
Morris JK, Savva GM. The risk of fetal loss following a prenatal diagnosis of trisomy 13 or trisomy 18. Am J Med Genet A. Apr 1 2008;146(7):827-32. [Medline].
Papageorghiou AT, Avgidou K, Spencer K, Nix B, Nicolaides KH. Sonographic screening for trisomy 13 at 11 to 13(+6) weeks of gestation. Am J Obstet Gynecol. Feb 2006;194(2):397-401. [Medline].
Pont SJ, Robbins JM, Bird TM, et al. Congenital malformations among liveborn infants with trisomies 18 and 13. Am J Med Genet A. Aug 15 2006;140(16):1749-56. [Medline].