We report on a prenatal diagnosis of ring chromosome 15 in a fetus with left congenital diaphragmatic hernia (CDH) and severe intrauterine growth restriction (IUGR). A 31-year-old woman, gravida 2 para 1, was referred because of increased nuchal translucency at gestational age of 13 weeks. Comprehensive fetal ultrasound examination was performed at 19 weeks revealing an early onset IUGR, left CDH with liver herniation, and hypoplastic nasal bone. Three-dimensional ultrasound (rendering mode) showed low set ears and depressed nasal bridge. Amniocentesis was performed with a result of a 46,XX,r(15) fetus after a cytogenetic study. A 1,430 g infant (less than third percentile) was born at 36 weeks. The infant presented with respiratory failure and died at 2 h of life. Postnatal karyotype from the umbilical cord confirmed the diagnosis of 15-ring chromosome. We described the main prenatal 2D- and 3D-ultrasound findings associated with ring chromosome 15. The interest in reporting the present case is that CDH can be associated with the diagnosis of 15-ring chromosome because the critical location of the normal diaphragm development is at chromosome 15q26.1-q26.2.
Ring chromosome 15 is a rare structural chromosomal abnormality. There are approximately 40 cases that have been reported in the literature [
The ring 15 chromosome syndrome results in a variable phenotype; however, there are some common findings. In a review of 25 cases from the literature, the main characteristics of this syndrome include intrauterine growth restriction (100%), variable mental retardation (95%), microcephaly (88%), hypertelorism (46%), and triangular facies (42%). Other frequent findings include delayed bone age (75%), brachydactyly (44%), speech delay (39%), frontal bossing (36%), anomalous ears (30%), café-au-lait spots (30%), cryptorchidism (30%), and cardiac abnormalities (30%) [
Therefore, a precise genotype-phenotype correlation is usually problematic [
We reported a prenatally diagnosed fetus at 19 weeks with ring chromosome 15 and severe IUGR associated with left congenital diaphragmatic hernia (CDH), which may have particular aspects involved in the genetic disease of this anomaly.
A 31-year-old female, gravida 2 para 1, with a 2-year-old healthy child, was referred to our Fetal Center because of increased nuchal translucency (3 mm) at 13 weeks, measured elsewhere. Doppler study of the ductus venosus and assessment of fetal nasal bones were not evaluated at that examination. No other structural abnormalities were described at that moment. The combined test, including ultrasound and biochemistry tests, was not performed in this patient because it is not routinely offered in our country because of the elevated costs. No prenatal invasive test was indicated before the patient was observed. At referral, a fetal comprehensive ultrasound exam was performed at 19 weeks using a SonoAce X8 apparatus (Samsung, Seoul, Korea) equipped with a convex volumetric multifrequency transducer (4–7 MHz). Fetal biometry revealed a biparietal diameter (BPD) of 38 mm (17 + 6 weeks), an abdominal circumference (AC) of 110 mm (16 weeks), and a femur length (FL) of 22 mm (16 + 6 weeks), indicating fetal growth restriction. Ultrasound examination also showed a large left CDH with liver herniation into the chest and hypoplastic nasal bone (Figure
Two-dimensional ultrasound finding in a fetus with ring chromosome 15 at 19 weeks of pregnancy showing liver herniation into the thorax due to congenital diaphragmatic hernia.
The nuchal fold thickness was 2.8 mm. The amniotic fluid index and arterial Doppler were normal. Subsequent ultrasound examination also showed dolichocephaly and clubfoot. Hands were small and remained constantly flexed, but eventually opened.
Three-dimensional ultrasound revealed low set ears and depressed nasal bridge (Figure
Three-dimensional ultrasound in the rendering mode findings in a fetus with ring chromosome 15 at 19 weeks of pregnancy. (a) Face fetus showing the low set ears. (b) Face fetus showing the depressed nasal bridge.
G banding of chromosomes revealed a ring chromosome 15, karyotype (46,XX,r(15)
Because there was a chromosomal abnormality but it was not possible to establish the prognosis, fetal surveillance was performed by fetal Doppler studies every 2 weeks because of the diagnosis of IUGR. The last ultrasound exam was performed at 36-week-gestation age, and fetal biometry revealed a BPD of 76 mm (30 + 3 weeks), an AC of 248 mm (29 weeks), and a FL of 54 mm (29 + 6 weeks), indicating severe IUGR.
A 1,430 g newborn (less than third percentile) was delivered by cesarean section at 36 weeks because of abnormal Doppler studies, following patient request. Apgar scores were 3, 6, and 7 at first, third, and fifth minutes of life. The newborn developed severe respiratory failure, leading to death in 2 h. All dysmorphic findings were observed after birth. Autopsy was not performed because the parents denied it. In addition, the parents denied any further genetic study on the fetus. The karyotype collected from the umbilical cord confirmed the diagnosis of 15-ring chromosome.
Ring chromosome 15 is a rare structural chromosomal abnormality that results from the loss of distal ends of both the p arm and q arm with union of both ends. There are four cases in prenatal diagnosis reported [
Liu et al. [
Glass et al. [
Hatem et al. [
Manolakos et al. [
According to previous reports in the literature, infants with ring chromosome 15 are compatible with life but usually have severe growth restriction during childhood. Although ring chromosome 15 is related to variable phenotypes, most recurrent findings are severe growth deficiency, mental retardation, and dysmorphic features [
IUGR is a common finding in fetuses with abnormal karyotype [
In the present case, three-dimensional ultrasound was helpful to provide more information on the fetal face and limbs. Three-dimensional ultrasound in the rendering mode was important in the assessment of facial deformations in the present fetus (low-set ears and depressed nasal bridge).
Most of the cases of ring chromosome 15 are diagnosed postnatal. Except for the diagnosis of IUGR, there are no specific ultrasound findings described in the literature that are related to this syndrome [
We reported a new case of prenatal diagnosis of ring chromosome 15 associated with severe phenotypes.
The authors declare that there is no conflict of interests regarding the publication of this paper.