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eMedicine Journal
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Pediatrics
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Genetics And Metabolic Disease
Patau Syndrome Synonyms, Key Words, and Related Terms: Patau syndrome, trisomy 13 syndrome, D1 trisomy syndrome, trisomy D syndrome, severe mental deficiency, viable autosomal trisomy, holoprosencephaly, hypotelorism, microphthalmia, anophthalmia, Edwards syndrome, aneuploidy, Robertsonian translocation |
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 | AUTHOR INFORMATION | Section 1 of 11    |
Authored by Robert G Best, PhD, FACMG, Director, Professor, Department of Obstetrics and Gynecology, Division of Genetics, University of South Carolina School of Medicine
Coauthored by James Stallworth, MD, Program Director, Associate Professor, Department of Pediatrics, Palmetto Richland Memorial Hospital, University of South Carolina
Robert G Best, PhD, FACMG, is a member of the following medical societies: American Association for the Advancement of Science, American College of Medical Genetics, and American Society of Human Genetics
Edited by Elaine H Zackai, MD, Director of Clinical Genetics Center, Professor of Pediatrics, Department of Pediatrics, Division of Human Genetics and Molecular Biology, University of Pennsylvania, Children's Hospital of Philadelphia; Mary L Windle, PharmD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy, Pharmacy Editor, eMedicine.com, Inc; Robert Anthony Saul, MD, Senior Clinical Geneticist, Greenwood Genetic Center; Clinical Professor, Department of Pediatrics, University of South Carolina; Daniel Rauch, MD, FAAP, Director, Pediatric Hospitalist Program, Associate Professor, Department of Pediatrics, New York University School of Medicine; and Bruce A Buehler, MD, Professor, Department of Pathology and Microbiology, Chairman, Department of Pediatrics, Director, Hattie B Munroe Center for Human Genetics, University of Nebraska Medical Center
| Author's Email: | Robert G Best, PhD, FACMG |  |
|---|---|---|
| Editor's Email: | Elaine H Zackai, MD |
eMedicine Journal, March 2 2006, VOLUME 7,
Number 3
| INTRODUCTION | Section 2 of 11  |
Background: Patau syndrome is the least common and the 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. Many of the clinical features are highly variable; 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, and heart defects also are 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. 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 is generally 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.
Frequency:
Mortality/Morbidity: Median survival age for children with Patau syndrome 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 Patau syndrome are rare.
Holoprosencephaly, a frequent brain malformation associated with Patau syndrome, 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 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 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. 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 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. 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.
| CLINICAL | Section 3 of 11 |
History:
Physical:
Causes: Although specific etiologic factors have not been identified, a significant association exists between Patau syndrome and increased maternal age. Aneuploidy is most often the result of nondisjunction during maternal meiosis I.
| DIFFERENTIALS | Section 4 of 11 |
Other Problems to be Considered:
Edwards syndrome
Partial duplication of 13q
| WORKUP | Section 5 of 11 |
Lab Studies:
Imaging Studies:
| TREATMENT | Section 6 of 11 |
Surgical Care: Surgical interventions are generally withheld for the first few months of life because of the high mortality rates of babies with Patau syndrome. 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.
Consultations: Referral to a geneticist or genetic counselor is important for appropriate counseling regarding recurrence risks, etiology, prognosis, and the availability of local area resources for support.
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 (ie, trisomy 21, trisomy 18) is approximately 0.5% above the mother's age-related risk for autosomal trisomies. 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. Consult a genetic counselor or medical geneticist regarding recurrence risks for structural rearrangements that involve chromosome 13.
Diet: In a group of 12 survivors with Patau syndrome, 4 were documented as requiring gavage feeding as newborns, and 7 were bottle-fed. Two children ate and drank with help prior to age 54 months, and feeding by spoon, finger, and cup was reported.
| MEDICATION | Section 7 of 11 |
Medical literature provides little information on the use of specific drugs to treat Patau syndrome.
| FOLLOW-UP | Section 8 of 11 |
Further Outpatient Care:
In/Out Patient Meds:
Deterrence/Prevention:
Prognosis:
Patient Education:
| MISCELLANEOUS | Section 9 of 11 |
Medical/Legal Pitfalls:
| TEST QUESTIONS | Section 10 of 11 |
CME Question 1: A newborn girl presents with low Apgar scores, bilateral cleft lip and palate, rocker-bottom feet, atrial septal defect, scalp defect (cutis aplasia), flexion of the fingers, and holoprosencephaly. Which of the following is the most likely diagnosis?
A: Amniotic band disruption sequence
B: Patau syndrome
C: Van der Woude syndrome
D: Down syndrome
E: Turner syndrome
The correct answer is B: Patau syndrome should be considered first because of the midline defects combined with cutis aplasia and the other described features. Amniotic band sequence might be considered because of the clefting and scalp defects, but the physician should suspect a syndrome of some kind because of the other clinical features that are not normally components of amniotic band disruption sequence. While Van der Woude syndrome is a genetic syndrome that does include facial clefting, that syndrome does not include any of the other features mentioned. Down syndrome and Turner syndrome are other chromosomal syndromes that may include heart defects, but these syndromes are rarely associated with clefting or midline defects.
CME Question 2: Which of the following common brain malformations is most often observed in Patau syndrome?
A: Hydrocephalus
B: Holoprosencephaly
C: Encephalocele
D: Porencephalic cyst
E: Dandy-Walker malformation
The correct answer is B: Patau syndrome includes cleavage abnormalities of the embryonic forebrain, resulting in such midline malformations as holoprosencephaly. Dandy-Walker malformation consists of agenesis of cerebellar vermis with resulting dilatation of the posterior fossa, causing hydrocephalus and enlargement of the head—in contrast to the microcephaly observed in trisomy 13. Neural tube defects, such as encephalocele, sometimes occur in children with Patau syndrome but at a much lower frequency than the rate associated with holoprosencephaly. Porencephalic cyst is usually caused by intrauterine or perinatal infarction or trauma and occurs in one hemisphere, often resulting in macrocrania.
Pearl Question 1 (T/F): Patau syndrome is the rarest and most severe of the autosomal trisomies found in live-born children.
The correct answer is True: Only 3 autosomal trisomies allow survival to live birth: trisomy 13, 18, and 21. Frequency of trisomy 21 (Down syndrome) is highest at 1 case per 800 live births. (By a large margin, Down syndrome has the mildest phenotype.) Trisomy 18 is intermediate in frequency and severity; its live-birth frequency is approximately twice that of trisomy 13.
Pearl Question 2 (T/F): Chromosomal analysis of a child with Patau syndrome is a necessary component of the workup.
The correct answer is True: Diagnosis of Patau syndrome requires demonstration of a full or partial trisomy of chromosome 13 by conventional cytogenetic methods. This is an important consideration in the differential diagnosis. Parental chromosome studies are also indicated if structural chromosome abnormalities are identified in the child. However, more often the extra copy of chromosome 13 is found as a freestanding trisomy.
Pearl Question 3 (T/F): Midline defects are infrequent in Patau syndrome.
The correct answer is False: Midline facial defects are seminal to the clinical suspicion of Patau syndrome. Severe midline facial defects correlate well with midline brain defects such as holoprosencephaly. Absence or severe malformation of the eyes and/or nose may be observed in cases involving the most severe expression of holoprosencephaly, ie, the alobar form.
Pearl Question 4 (T/F): Recurrence risks for mothers who have given birth to an infant with Patau syndrome are the same as for women with no family history of Patau syndrome.
The correct answer is False: In general, recurrence risks for women who have given birth to a child with Patau syndrome are increased over the general population, but the magnitude of the increase depends on the chromosomal form of the trisomy. Freestanding trisomy 13 has a recurrence risk of about 0.5% over the age-related risks for autosomal trisomies. Recurrence risks may be substantially higher when the baby has a structural chromosome abnormality involving chromosome 13.
| BIBLIOGRAPHY | Section 11 of 11 |
| NOTE: |
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