A new case of Casamassima-Morton-Nance (CMN) syndrome presenting prenatally as VACTERL association

Introduction

Casamassima-Morton-Nance (CMN) syndrome (OMIM 271520) is a disorder that has considerable overlap with spondylocostal dysostosis and Vertebral, Anorectal, Cardiac, Tracheo-Esophageal, Radial/Renal, Limb (VACTERL) association but with consistent features of anal and urogenital abnormalities, particularly ambiguous/absent genitalia. Since the original report of CMN, it has become clear that some of these distinguishing features may enable prenatal diagnosis of CMN by ultrasound. CMN syndrome is an important diagnosis to consider because of the difference in prognosis for this condition compared to the more common and prognostically more favorable VACTERL association. Since the first two cases described in 1981, there have been four reported cases of CMN syndrome, all with characteristic vertebral segmentation defects, rib anomalies, anal atresia and urogenital abnormalities. Here we present a further case of CMN syndrome, the seventh reported in the literature to date, in which VACTERL association was considered to be the most likely diagnosis prenatally.

Case report

The mother was a healthy, 23-year-old, G3P2 Caucasian woman in a non-consanguineous relationship. Her previous two children were born at term with no known abnormalities or complications. There was a history of mild scoliosis (with normal vertebral bodies on X-ray) in the father but no other family history of scoliosis or other skeletal abnormalities.

First trimester screening at 12 weeks of gestation revealed a normal serum screen but an increased nuchal translucency (3.1 mm, >99^th percentile).

The morphology ultrasound scan done at 20 weeks of gestation identified a scoliosis, abnormal appearing kidneys (described below) and a thickened nuchal fold (9.1 mm, >99^th percentile). The stomach and bladder were difficult to assess during the study and a second opinion morphology scan was sought.

A follow-up ultrasound was done at 21 weeks gestation, which confirmed the scoliosis and demonstrated multiple segmentation anomalies within the spine, particularly involving the thoracic spine and sacrum. In addition, there were bilaterally enlarged kidneys and the left kidney had the appearance of a multi-cystic dysplastic kidney (Figure 1). The bladder was not visible and there was a small stomach and severe oligohydramnios, limiting visualization. No genital abnormalities were reported prenatally. Biparietal diameter, abdominal circumference, foot length and long bone length were all normal. Given the vertebral abnormalities, small stomach, and renal abnormalities, VACTERL association was considered the most likely diagnosis with caudal regression and a variant of spondylocostal dysostosis on the differential diagnosis list.

Figure 1

Appearance of kidneys at 20-week morphology ultrasound. Enlarged right kidney with pelvicaliectasis and left multicystic dysplastic kidney (markers).

The couple were counselled and they elected for termination of pregnancy at 22 weeks of gestation. Consent limited the autopsy examination to external fetal examination and radiological survey only. This revealed coarse facial features with a posteriorly rotated right ear, broad nasal bridge, mild micrognathia and an elongated philtrum (Figure 2). The fetus had a short webbed neck with nuchal thickening. There was scoliosis convex to the right. There was ulnar deviation of the left hand and bilateral talipes, both considered to be positional effects from the oligohydramnios. Both hands were enlarged, broad, and there was a prominent gap between the index and middle fingers bilaterally. The external genitalia was ambiguous. The fetus had anal agenesis and meconium was found at the opening of the external genitalia, which suggested the presence of a recto-vaginal fistula or similar anatomical arrangement. There was a single umbilical artery.

Figure 2

External examination of fetus revealing short neck, narrow thorax, ambiguous genitalia, and prominent large hand with large gap between index and middle fingers.

The fetal skeletal survey confirmed vertebral abnormalities extending from T2 to T12, including hemivertebrae, butterfly vertebrae, and block vertebrae resulting in shortening of the thoracic spine. There was some asymmetry of the lateral ossification centers within the lumbar spine (Figure 3). There were also several severe rib defects. Bilaterally, ribs one to six were thin and short with rib fusion at several levels. The lower ribs were gracile bilaterally.

Figure 3

Fetal skeletal survey showing multiple segmental abnormalities extending from T2 to T12 including hemivertebrae, butterfly vertebrae and block vertebrae, severe bilateral rib anomalies, and large hands with a prominent gap between index and middle fingers.

X-rays of the long bones, hands and feet were normal. The cervical vertebrae had a normal appearance but the neck appeared to be short.

Routine chromosome analysis revealed a normal 46,XY male karyotype with no chromosomal abnormality detected. Array CGH was not done.

Radiologically, the possibility of spondylocostal dysostosis or Jarcho-Levin syndrome was considered given the extensive abnormalities of both the vertebrae and ribs. However, ambiguous/absent external genitalia has been described in previous cases of CMN syndrome and when combined with anal atresia and features of spondylocostal dysostosis, as in our case, CMN syndrome was the most likely diagnosis.

Discussion

The first report of CMN syndrome described two affected siblings from a consanguineous Mennonite family, suggesting autosomal recessive inheritance [1]. No causal gene or mutation has been identified; however, potential loci have been suggested by separate reports of a translocation involving chromosomes 6 and 9 and a deletion at chromosome 8p23.1 [2, 3].

The diagnosis of CMN syndrome can be made when the combination of vertebral/rib abnormalities similar to spondylocostal dysostosis occurs with anal atresia and abnormalities of external genitalia. There is variability in the severity of these abnormalities within the individual cases described (Table 1). A previous case exhibited typical significant vertebral and rib abnormalities including absent vertebrae, short, thin and abnormally shaped ribs but with normal kidneys and ureters [2]. The case presented by Aguinaga et al. had a less severe vertebral phenotype (only thoracic hemivertebrae), rib anomalies, and bilateral hydronephrosis [4]. In the present case, both vertebral/rib and urinary tract abnormalities were severe; in addition to hydronephrosis and a non-visible bladder, a multicystic dysplastic left kidney was identified, which has not been described in any of the previous cases. An increased nuchal translucency has not been described in CMN syndrome before. Absent or ambiguous genitalia has been a consistent feature in the cases described and it is an important clinical sign that discriminates between CMN syndrome and other similar conditions such as VACTERL and spondylocostal dysostosis [2, 5]. Specific emphasis on the antenatal detection of ambiguous genitalia in this setting may be helpful. Unfortunately, in our case there were inherent difficulties with this because of severe oligohydramnios. However, we suggest that careful prenatal ultrasound assessment of the genitalia in cases of suspected VACTERL is important in differentiating this condition from CMN syndrome. The presence of rib abnormalities on prenatal ultrasound is also a key feature of CMN syndrome.

Our case is the seventh reported case of CMN syndrome and adds to our understanding of this condition. The additional feature of multicystic dysplastic kidney has not been described before.