Women"s Health Alliance, Nashville Tennessee. * Genetics Associates Inc. Nashville Tennessee.

Chromosomes are highly dynamic structures with a tightly regulated organization. Normal DNA replication results in two linear sister chromatids organized in a parallel configuration so that symmetrical separation can occur at the metaphase-anaphase transition. However, a change in topology from linear to circular may totally disrupt this sequence of events.

Definition: Circular topology of a chromosome is called a  "ring chromosomeâ€. There are two ways in which a ring chromosome can be formed:

1. Two DNA breaks, one in each arm of the same chromosome followed by fusion of the proximal broken ends, and,
2. By fusion of dysfunctional telomeres (end-terminal part) from the same chromosome.

On rare occasions, ring chromosomes are found as constitutional aberrations in fetuses or newborn with developmental abnormalities. More commonly, they may arise as acquired genetic abnormalities in cells from tumors or leukemias.

Case report:

This is a 27 year-old patient with an otherwise unremarkable pregnancy.

The following images were obtained during an ultrasound examination performed at 20 weeks of gestation.

Fetal head is normal.

In this image we can clearly see the head to abdomen disproportion.

Fetal thorax show an enlarged heart (cardiothoracic ratio 50%).

No stomach was visible in any of the ultrasound examinations performed to this patient.

Single umbilical artery was demonstrated with color Doppler.

The fetal biometry parameters show a 3-week discordance between abdomen and skeletal measurements. There was also a 2-week discordance between abdominal and head perimeters.

• Biparietal diameter :                 42.9 mm 18w1d
• Head perimeter:                        169 mm 19w3d
• Abdominal perimeter:                125 mm 17w6d
• Humerus:                                    30.3 mm 20w0d
• Femur:                                           33 mm 20w3d

X-ray rendering of the fetal spine. The coronal view clearly shows that this baby had no scoliosis.

Same rendering of sagittal view of the fetal spine showing thoracic kyphosis.

The fetal over-flexed position is seen in this next picture.

In view of all these findings, an amniocentesis was performed. The FISH study (Fluorescent in-situ hybridization) returned normal. But, the conventional cytogenetic study, showed the following:

46, XX, r (14) (p11.2q32) [13]/ 45, XX, - 14 [7]

What does this mean?

In conventional cytogenetics, the geneticist usually analyses 20 metaphases. In this case, out of the 20 analyzed cells, 13 featured a female karyotype (46, XX), with a ring chromosome derived from chromosome 14 [r (14)] . The remaining seven metaphases showed monosomy 14 (45, XX, -14). The ring chromosome is formed by the breakage of p-ter (chromosome 14 short arm terminal portion), which is p11.2, and the q-ter (chromosome 14 long arm terminal portion), which is q32. This means that the chromosome breaks on both sides of the chromosome 14 centromere and these ends then fuse, giving rise to this "ring chromosome".

These following two images show both genetical conditions:

First the ring chromosome 14 (highlighted in red)

The other cellular line encountered with the missing chromosome 14 (monosomy 14).

Prevalence: Unknown.
Pathogenesis: Ring Chromosome can be a sporadic (de-novo) or transmitted by a carrier parent (often mother).
Sonographic findings: Nuchal cystic hygroma , hypoplastic corpus callosum, IUGR .
Differential diagnosis: Any severe chromosomal anomaly that presents with early onset IUGR, dysgenesis of corpus callosum or cystic hygroma.
Associated anomalies (reported after birth):

• General: Growth delay.
• Skull: Microcephaly.
• CNS: Brain: atrophy, mild dilation of the lateral ventricles.
• Face: "Ring 14 facial dysmorphism or phenotypeâ€:
  • Narrow, elongated face
  • Narrow palpebral fissure
  • Epicanthus
  • Flat nasal bridge
  • Retrognathia
• Ocular: These anomalies are a constant feature: retinal dystrophia, which may be specific of the syndrome consists of a hyperpigmentation and sometimes, yellow-white flecks in the macula, and yellow-white spots in the mid-peripheral retina. (These ophthalmic changes are usually concomitant to a breakpoint at 14 q 32.2.4 11).
• Genital: hypoplastic scrotum.
• Limbs: lymphoedema of hands and feet, brachydactyly of fingers and toes.
• Neurological: Different degrees of developmental delay and mental deficiency, early onset seizures (generalized or partial complex type)
• Other: tendency to pulmonary infections, a disorder of skin pigmentation and generalized hypotonia .

Recurrence risk: Depends of etiology.

Management: When a ring chromosome is encountered, a thorough parental chromosomal examination must be made in order to determine if it is a punctual mutation or if it is a transmitted chromosomal anomaly from a parent.

References

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