Search :     
Articles » Aneuploidy

2001-04-24-14 Trisomy 16 © Quintero www.thefetus.net/


Trisomy  16 

Juan Carlos Quintero M. MD, Pamela Crum, RDMS, Philippe Jeanty MD, PhD

 Cali Colombia and Nashville, TN

 

Synonyms: trisomy confined to the placenta; confined placental mosaicism; uniparental isodisomy for chromosome 16; uniparental heterodisomy for chromosome 16[1],[2].

Definition: Trisomy of chromosome 16. The unbalanced karyotype may result from the segregation of a parental translocation (maternal origin usually). The syndrome may also result from a partial trisomy of 16p or 16q.

Case report:  

This fetus was scanned at 18 weeks and 1 day menstrual age. All the biometry was consistent with 17 weeks days. The patient had no rupture of the membranes.

Biparietal diameter

36.5 mm 

16w +2d 

Head perimeter

139

17w+ 1d

Femur

24

17w+ 2d

Humerus

22.4

16w+ 6d

Abdomen perimeter 

125.5

 

The following images were obtained and all appear fairly unremarkable aside from the growth retardation, the placentomegaly and the severe oligohydramnios.

  

  

Normal heart

 

The abdomen, stomach ands kidneys

  

  

  

  

 

The limbs

The spine

Placenta and cervix

  

The findings were: 

  • mild growth retardation, 

  • placentomegaly and 

  • severe oligohydramnios.

The kidneys were visible and aside from a small amount of pyelectasis were unremarkable (no cysts in particular). In particular the renal arteries were present. The bladder was also seen, and was not distended, which excluded some of the cystic renal disorders and the bladder outlet obstructions. Thus the oligohydramnios was not related to a renal problem. Since there was no history of TORCH infection, an aneuploidy was likely and since the fetus was fairly unremarkable, it was suggested that the source of this fetus problem was an aneuploidy or mosaicism of the placenta, and in particular trisomy 16.

In view of the findings the patient was counseled, but she declined to not have a karyotype performed. The fetus spontaneously died at 35 weeks.

Prevalence: Rare. Sex ratio:

  • Trisomy 16p: M4:F8,
  • Trisomy 16q: M8:F10 (observed)1.

In the late first trimester this is equivalent to 150:10,000 recognized pregnancies.

Etiology: The partial trisomies result not due to non-disjunction, but to either failure of bivalent formation or the precocious separation of bivalent homologues (with or without crossing-over) during maternal meiosis I[3] . Almost all cases are mosaic. Some mosaics are the result of trisomic rescue (the loss of a 3rd chromosome, resulting in a normal number of chromosomes but the 2 remaining chromosome may come from one parent – a uniparental disomy--). Trisomy 16q and 16p have similar implications in early miscarriages. Families with rearrangements involving chromosome 16 frequently show early pregnancy losses.

Pathogenesis: Unknown. Trisomy 16 is the most common autosomal trisomy seen in early spontaneous abortion, (15% of first trimester trisomies). Most pregnancies are lost around 12 weeks and 10 % undergo reduction to disomy and continuing to second trimester12 There are few cases of live births reported and the most of theme have a growth failure, psychomotor retardation and early death[4]. The difference between the  cases that are lost early in pregnancy and those which survive is that in the former the cells in the inner cell mass, destined to form the fetus proper , are in part aneuploid , and in the latter they are not12 . In the majority of cases the abnormal karyotype is confined to the placenta and in the fetus may be normal or a mosaic.

Sonographic findings:

First trimester:

  • small embryo for the gestational sac,
  • poorly shaped embryo.

Second trimester:

  • short neck in the most of cases;
  • ventricular and atrial septum defects,
  • abnormal branching of the aortic archs1,[5]
  • malrotation of the gut (33%)
  • diaphragmatic hernia
  • genital anomalies in most male patients (ambiguous genitalia, hypospadias, small penis)
  • the anus is abnormal in most of the cases with anterior displacement and imperforation
  • growth restriction is the most consistent finding in the second and third trimester;
  • oligo and polyhydramnios;
  • skeletal maturation is delayed and camptodactyly is present in more than one half of the cases.

Clinical findings: 

Table: Clinical findings

CVS

Amnio

Placenta (at birth)

Skin

Ultrasound

Outcome

 

47,XX+16

46,XX

46,XX

 

950 g, vsga died 4 hours.[6]

47,XX+16

46,XX

47,XX+16

46,XX

 

 

272 g, sga.[7]

47,XY+16

 

46,XY

46,XY

 

2210 g, sga.[8]

47,XY+16

46,XY

47,XY+16

 

 

2043 g, sga.[9]

47,XX+16

46XX

47,XX+16

46,XX

 

Placental

Sonulencies

VSD

Sga.[10].

47,XX+16

47,XX+16

46,XX

46,XX

IUGR, enlarged placenta

1631 g, vsga, died at 2 weeks.[11]

47,XY+16

46,XY

 

 

 

3090 g, 38+1 weeks, normal.[12]

 

46,XY 47XY+16

47,XY+16

 

Clinodactyly, ASD

TOP (20 weeks).[13]

47,XX+16

46XX

 

46XX

Hydrocephaly, IUGR,

IUD (at 25 weeks) polysplenia, ACC.[14]

47,XX+16

46,XX

46,XX

46,XX

Placental sonolucencies, SUA, IUGR, VSD

Polyhydramnios

1880 g, vsga,muscular VSD.[15]

vsga = very small for gestational age

sga = small for gestational age

Differential diagnosis: other trisomies. The diagnosis is more common by chorionic villus sampling early in pregnancy than with amniocentesis. The fetal karyotype can be normal or a mosaic.

 

Associated anomalies: Craniofacial anomalies like high forehead or frontal bossing and enlarged metopic suture, prominent nose, hypertelorism, cleft lip and palate; pectus excavatum, hypoplastic sternum; scoliosis with or without kyphosis, multiple vertebral anomalies  (hemivertebra