Patau Syndrome (Trisomy 13)

Overview

Plain-Language Overview

Patau Syndrome, also known as Trisomy 13, is a rare genetic disorder caused by the presence of an extra copy of chromosome 13. This condition leads to severe intellectual disability and multiple physical abnormalities. Babies with Patau Syndrome often have problems with their heart, brain, and other organs. Common features include a small head, cleft lip or palate, and extra fingers or toes. Most infants with this syndrome have a shortened life expectancy due to the severity of their health issues.

Clinical Definition

Patau Syndrome is a chromosomal disorder characterized by trisomy 13, where there is an extra full or partial copy of chromosome 13 in the cells. This results in a constellation of severe congenital anomalies including central nervous system malformations such as holoprosencephaly, microcephaly, and neural tube defects. Craniofacial abnormalities commonly include cleft lip and/or palate, microphthalmia, and low-set ears. Cardiac defects such as ventricular septal defects and patent ductus arteriosus are frequent. Limb abnormalities include polydactyly and rocker-bottom feet. The syndrome is associated with profound intellectual disability and failure to thrive. Most affected infants die within the first year of life due to complications like respiratory failure or cardiac defects. Diagnosis is confirmed by karyotyping or chromosomal microarray analysis. The condition arises from nondisjunction during meiosis, leading to an extra chromosome 13. Mosaicism and Robertsonian translocations involving chromosome 13 can also cause the syndrome. Prenatal screening and diagnostic tests can identify the disorder before birth.

Inciting Event

The inciting event is usually a meiotic nondisjunction during gametogenesis resulting in an extra chromosome 13.
Less commonly, Robertsonian translocation involving chromosome 13 can cause the syndrome.

Latency Period

none

Diagnostic Delay

none

Clinical Presentation

Signs & Symptoms

Severe intellectual disability and developmental delay.
Characteristic facial abnormalities including microphthalmia and cleft lip/palate.
Multiple congenital anomalies such as polydactyly and scalp defects.
Feeding difficulties due to orofacial malformations.
Seizures and hypotonia are common neurological features.

History of Present Illness

Newborn presents with multiple congenital anomalies including cleft lip/palate, microphthalmia, and polydactyly.
Severe feeding difficulties and respiratory distress are common in the neonatal period.
There may be signs of congenital heart defects such as murmurs or cyanosis.

Past Medical History

none

Family History

Family history may reveal parental balanced translocations involving chromosome 13.
Previous pregnancies with chromosomal abnormalities or miscarriages may be reported.

Physical Exam Findings

Presence of microphthalmia or anophthalmia is common.
Midline facial clefts such as cleft lip and/or palate are frequently observed.
Polydactyly, especially postaxial polydactyly, is a typical finding.
Scalp defects known as cutis aplasia may be present.
Congenital heart murmurs due to structural defects are often detected.
Microcephaly with a prominent forehead is characteristic.

Diagnostic Workup

Diagnostic Criteria

Diagnosis of Patau Syndrome requires identification of trisomy 13 through chromosomal analysis, typically karyotyping or microarray. Clinical features supporting diagnosis include midline facial defects such as cleft lip and palate, central nervous system anomalies like holoprosencephaly, polydactyly, and congenital heart defects. The presence of multiple major congenital anomalies combined with cytogenetic confirmation establishes the diagnosis.

Pathophysiology

Key Mechanisms

Patau syndrome results from trisomy 13, where there is an extra copy of chromosome 13 in all or some cells.
The presence of an extra chromosome 13 leads to abnormal gene dosage affecting multiple organ systems during embryonic development.
This chromosomal abnormality causes severe congenital malformations including central nervous system, cardiac, and craniofacial defects.

Involvement	Details
Organs	Brain shows severe malformations including holoprosencephaly and microcephaly.
	Heart commonly has defects such as ventricular septal defects and atrial septal defects.
	Kidneys may have cystic dysplasia or other structural abnormalities.
Tissues	Neural tissue is severely malformed, often showing holoprosencephaly and other midline defects.
Tissues	Cardiac tissue frequently exhibits structural abnormalities leading to congenital heart disease.
Cells	Neural progenitor cells are affected leading to severe brain malformations such as holoprosencephaly.
Cells	Cardiomyocytes may be abnormal contributing to congenital heart defects common in this syndrome.
Chemical Mediators	Apoptotic mediators are involved in abnormal cell death contributing to developmental defects.
Chemical Mediators	Growth factors such as fibroblast growth factors may be dysregulated affecting organogenesis.

Treatment

Pharmacological Treatments

Supportive care medications
- Mechanism: Symptomatic management of complications such as seizures or infections
- Side effects: Vary depending on medication used

Non-pharmacological Treatments

Multidisciplinary supportive care including physical, occupational, and speech therapy to improve developmental outcomes.
Surgical interventions to correct congenital malformations such as cleft lip/palate or cardiac defects when feasible.
Genetic counseling for families to understand recurrence risk and implications.

Prevention

Pharmacological Prevention

none

Non-pharmacological Prevention

Prenatal genetic counseling for at-risk couples to discuss recurrence risk.
Prenatal screening with ultrasound and cell-free fetal DNA testing for early detection.
Preimplantation genetic diagnosis during in vitro fertilization to select unaffected embryos.

Outcome & Complications

Complications

Respiratory failure due to central nervous system and structural abnormalities.
Congestive heart failure from severe cardiac defects.
Feeding difficulties leading to malnutrition and failure to thrive.
Seizure disorders causing neurological deterioration.

Short-term Sequelae	Long-term Sequelae
High neonatal mortality due to multiple organ malformations. Severe feeding problems requiring specialized nutritional support. Early onset seizures and neurological decline. Respiratory distress from airway anomalies and central apnea.	Profound intellectual disability with minimal developmental progress. Chronic respiratory insufficiency due to structural and neurological defects. Persistent feeding difficulties necessitating gastrostomy. Severe growth retardation and failure to thrive.

Differential Diagnoses

Patau Syndrome (Trisomy 13) versus Cri-du-chat Syndrome

Patau Syndrome (Trisomy 13)	Cri-du-chat Syndrome
Polydactyly and midline defects such as cleft lip/palate are typical of Patau syndrome but absent in Cri-du-chat syndrome.	High-pitched cat-like cry is a hallmark symptom.
Holoprosencephaly and scalp defects (cutis aplasia) are seen in Patau syndrome but not in Cri-du-chat syndrome.	Microcephaly with severe intellectual disability is prominent.
Chromosome 13 trisomy causes Patau syndrome, whereas Cri-du-chat results from a deletion on chromosome 5p.	Hypertelorism and epicanthal folds are common facial features.

Patau Syndrome (Trisomy 13) versus Down Syndrome (Trisomy 21)

Patau Syndrome (Trisomy 13)	Down Syndrome (Trisomy 21)
Severe CNS malformations such as holoprosencephaly are typical of Patau syndrome but not Down syndrome.	Upward slanting palpebral fissures and epicanthal folds are classic facial features.
Polydactyly and scalp defects (cutis aplasia) are seen in Patau syndrome but not in Down syndrome.	Single transverse palmar crease is commonly seen.
Congenital heart defects in Patau syndrome often include ventricular septal defects and atrial septal defects, whereas Down syndrome is more associated with atrioventricular septal defects.	Hypotonia is a prominent early finding.

Patau Syndrome (Trisomy 13) versus Edwards Syndrome (Trisomy 18)

Patau Syndrome (Trisomy 13)	Edwards Syndrome (Trisomy 18)
Holoprosencephaly and midline facial defects such as cleft lip/palate are typical of Patau syndrome.	Clenched fists with overlapping fingers (index over middle) are characteristic.
Polydactyly (extra digits) is frequently present in Patau syndrome but rare in Edwards syndrome.	Rocker-bottom feet deformity is commonly observed.
Cutis aplasia (scalp defects) is a distinctive feature of Patau syndrome.	Micrognathia is more prominent than in Patau syndrome.