Atlas of Genetic Diagnosis and Counseling || Trisomy 13 Syndrome

Trisomy 13 Syndrome

In 1960, Patau et al. first recognized the relation of

trisomy 13 to a clinical syndrome. Incidence is esti-

mated to be 1/4,000–1/10,000 live births.

Synonyms and Related Disorders

Patau syndrome

Genetics/Basic Defects

1. Trisomy 13

a. Mechanism: due to meiotic nondisjunction

i. Maternal origin of the extra chromosome

(90%)

ii. Stage of nondisjunction: mostly maternal

meiosis I (vs. meiosis II in trisomy 18)

iii. Paternal origin of the extra chromosome

(10%): The majority is primarily postzygotic

mitotic errors.

b. Frequency: 75% of cases

2. Translocation trisomy 13

a. Mechanism: de novo (75%) or familial transmis-

sion (25%)


c. Trisomy 13 due to t(13;13): The structural abnor-

malities are usually isochromosomes originating

in mitosis.

3. Mosaic trisomy 13

a. Mechanism: due to postzygotic (postferti-

lization) mitotic nondisjunction


c. Variable phenotype from full trisomy to near

normal

d. Variable mental retardation with longer

survival

e. Trisomy 13/triploidy mosaicism: a rare event

4. Partial trisomy 13

a. Partial trisomy of proximal segment with

nonspecific clinical features and little similarity

to full trisomy 13

b. Partial trisomy of distal segment with specific

clinical features

Clinical Features

1. General

a. Low birth weight

b. Thrombocytopenia

2. CNS

a. Severe mental retardation

b. Holoprosencephaly

c. Seizures

d. Central apnea

3. Craniofacial abnormalities

a. Microcephaly

b. Wide sagittal sutures

c. Wide fontanels

d. Scalp defect (aplasia cutis congenita, 50%)

e. Capillary hemangioma of the forehead

f. Ocular abnormalities

i. Microphthalmia/anophthalmia

ii. Colobomas

iii. Retinal dysplasia

g. Cleft lip/palate

h. Abnormal auricles

i. Low-set ears

j. Sensorineural and conductive deafness

H. Chen, Atlas of Genetic Diagnosis and Counseling, DOI 10.1007/978-1-4614-1037-9_235,# Springer Science+Business Media, LLC 2012

2057

k. Recurrent otitis media

l. Abundant nuchal skin folds

4. Cardiovascular abnormalities

a. Ventricular septal defect

b. Atrial septal defect

c. Patent ductus

d. Coarctation of the aorta

e. Dextrocardia

5. Gastrointestinal abnormalities

a. Omphalocele

b. Malrotation

c. Umbilical hernia

d. Inguinal hernia

e. Accessory spleen

f. Heterotopic pancreatic tissue

g. Meckel’s diverticulum

h. Diaphragmatic defects

i. Large gallbladder

6. Genitourinary abnormalities

a. Polycystic kidneys

b. Cryptorchidism

c. Hypospadias

d. Bicornuate uteri

e. Abnormal fallopian tubes

f. Hypoplastic ovaries

7. Skeletal abnormalities

a. Polydactyly

b. Posterior prominence of heel

c. Flexed fingers

d. Hypoplasia of pelvis

e. Shallow acetabulum

f. Thin posterior ribs

g. Flexion deformity of large joints

h. Limb deficiency (5.3%)

i. Radial aplasia

j. Hyperconvex narrow fingernails

8. Dermatoglyphics

a. Transverse palmar crease

b. t0

c. Hallucal arch fibular or loop tibial

9. Others

a. Thymic cyst

b. Persistence of fetal hemoglobin

10. Prognosis

a. Majority of trisomy 13 conceptuses

i. Abort during pregnancy

ii. Stillborn

b. Twenty-five percent die by 24 h of life

c. Forty-five percent die by 1 month of life

d. Sixty percent die by 6 months of life

e. Seventy-two die by 1 year of age

f. Usual mode of death: primary apnea

g. Survivals up to 11 and 19 years old reported

11. Mosaic trisomy 13

a. The phenotype ranges

i. Typical features of trisomy 13

ii. More mild mental retardation or even nor-

mal intellectual function (rare), milder phys-

ical features, and longer survival

b. The range in clinical severity is likely due to the

varying proportion of trisomy 13 cells and their

distribution within the body.

12. Partial trisomy 13 of the proximal segment


b. Large nose

c. Short upper lip

d. Receding mandible

e. Clinodactyly of the fifth fingers

13. Partial trisomy 13 of the distal segment


b. Bushy eyebrows (synophrys) with long

incurved lashes

c. Frontal capillary hemangioma

d. Long philtrum

e. Prominent antihelix

Diagnostic Investigations

1. Cytogenetic studies

a. Conventional technique

b. FISH of interphase cells for rapid diagnosis

c. Parental karyotyping in case of translocation tri-

somy 13

d. Trisomy 13 mosaicism

2. Echocardiography for cardiovascular anomalies

3. EEG: hypsarrhythmia

4. CT/MRI for central nervous system anomalies

5. Radiography

a. Wide anterior fontanel

b. Presence of a cervical rib

c. Absence of the 12th rib

d. Anomalies of rib morphology

e. Low acetabular angle

f. Long distal phalanges

g. Cranial bone abnormalities in case of

holoprosencephaly

h. Clefting of the vertebral bodies

2058 Trisomy 13 Syndrome

i. Abnormal postsphenoid component of the

sphenoid bone

j. Agenesis of the nasal bones

6. Placenta: Partial molar change of the placenta may

rarely occur in trisomy 13 (Has et al. 2002).

Genetic Counseling

1. Recurrence risk

a. Patient’s sib

i. Trisomy 13: about 1 in 4,000

ii. De novo translocation: about 1 in 4,000

iii. Familial translocation: 5–15%

iv. Mosaicism: 1 in 4,000

b. Patient’s offspring: not surviving to reproductive

age

2. Prenatal diagnosis

a. Prenatal ultrasonography: prevalence of ultra-

sound abnormalities (91%)

i. General

a) IUGR (48%)

b) Single umbilical artery

c) Polyhydramnios (15%)

d) Oligohydramnios (12%)

ii. Cranium and CNS abnormalities (58%)

a) Holoprosencephaly (39%)

b) Neural tube defects

c) Lateral ventricular dilatation without

holoprosencephaly (9%)

d) Enlarged cisterna magna or Dandy-

Walker variant (15%)

e) Microcephaly (12%)

f) Linear branching echogenicity of the

thalamus or basal ganglia (representing

vasculopathy)

g) Choroid plexus cyst

iii. Facial anomalies

a) Cyclopia

b) Proboscis

c) Hypotelorism

d) Hypoplastic midface

e) Cleft lip/palate (36%)

f) Micrognathia

iv. Neck anomalies

a) Nuchal thickening

b) Cystic hygroma

c) Hydrops

d) Lymphangiectasia

v. Chest/cardiac abnormalities

a) Diaphragmatic hernia

b) Ventricular septal defect

c) Hypoplastic left heart

d) Echogenic chorda tendineae (30%)

vi. Renal abnormalities (33%)

a) Echogenic kidneys

b) Pyelectasis

c) Enlarged kidneys

d) Hydronephrosis

vii. Abdominal abnormalities

a) Omphalocele

b) Echogenic bowel (6%)

c) Bladder exstrophy

viii. Limb abnormalities (33%)

a) Clenched and overlapping digits

b) Polydactyly

c) Radial aplasia

d) Short femur length

e) Talipes equinovarus

f) Rocker bottom feet

b. Chromosome analyses

i. Amniocentesis

ii. CVS, followed by amniocentesis

iii. Fetal cells isolated from maternal

blood using either flow sorting or magnetic

sorting

c. Dilemma for genetic counseling with trisomy 13

mosaicism

i. Infrequent occurrence

ii. Single-cell pseudomosaicism (3.3%)

iii. Multiple-cell pseudomosaicism (4%)

iv. Often represents pseudomosaicism or con-

fined placental mosaicism

v. True fetal mosaicism (in the context of low-

level single-digit percentage mosaicism):

not necessarily associated with congenital

defects and/or mental abnormalities

vi. An optimistic approach in case of normal

ultrasonography and absence of trisomy 13

cells in the fetal blood

vii. Possibility of adverse phenotype and intel-

lectual function in case of true low-level

fetal mosaicism

3. Management

a. Feedings

i. Nasal tube feeding

ii. Oral gastric tube feeding

iii. Gastrostomy feeding

Trisomy 13 Syndrome 2059

b. Nissan fundoplication for gastroesophageal

reflux

c. Risk for anesthesia

d. Early intervention programs

e. Seizure control

f. Monitor apneic spells

g. Treat infections

h. Symptomatic treatment for heart failure

i. Cardiac operation rarely performed

References

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a bFig. 1 (a, b) An infant with

trisomy 13 showing

microcephaly,

microphthalmia, forehead

hemangioma, cleft lip/palate,

and postaxial polydactyly

baFig. 2 (a, b) An infant with

trisomy 13 showing

microcephaly,

microphthalmia, cleft lip/

palate, and omphalocele


a bFig. 3 (a, b) Postaxialpolydactyly of the hand and

the feet in an infant with

trisomy 13


trisomy 13 showing

microcephaly, forehead

hemangioma, upslanted

palpebral fissures, cleft lip/

palate, and short neck


trisomy 13 showing scalp

defect on the vertex


Fig. 6 Another infant with trisomy 13 showing microphthalmia

and cleft lip/palate


a b

c

Fig. 7 (a–c) A neonate with

trisomy 13 showing

ethmocephaly, transverse

reduction of the left forearm,

and polydactyly of the right

hand and both feet


Fig. 9 An infant with trisomy 13-Klinefelter syndrome showing

hypotelorism and a single nostril (holoprosencephaly)

Fig. 8 A child with trisomy 13 associated with premaxillary

dysgenesis, hypotelorism, cleft nose, and smooth philtrum

b c

ed

aFig. 10 (a–e) A neonate with

trisomy 13 showing similar

facial features. In addition, the

infant has polydactyly.

Prenatal ultrasound

examination showed

microcephaly, scalp edema,

and holoprosencephaly (a

normal ultrasound at the same

gestation is given here)


1

6 7 8 9 10 11 12

181716151413

19 20 21 22 X Y

2 3 4 5

Fig. 11 Trisomy 13 karyotype (G-banded)

1

6 7 8 9 10 11 12

181716151413

19 20 21 22 X Y

2 3 4 5

Fig. 12 Translocation of trisomy 13 karyotype [t(13q;14q)]

Fig. 13 Trisomy 13 shown by FISH analysis of interphase cells

with three copies of the green signal (LSI 13/SpectrumGreen)

representing three chromosome 13s and two copies of the red

signal representing two chromosome 21s (LSI 21/

SpectrumOrange)


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Atlas of Genetic Diagnosis and Counseling || Trisomy 13 Syndrome