Ring chromosome 2 was first described in 1981, encompassing a set of common phenotypic characteristics such as short stature, nonspecific dysmorphic features and varying degrees of psychomotor retardation.1 Ninety-nine percent of cases are sporadic.2 Ring chromosome 2 is a rare chromosomal abnormality, with few cases described in the medical literature.2,3

We present the case of a male patient aged 12 months. Symmetrical intrauterine growth restriction (IUGR) had been detected at 22 weeks’ gestation. The patient was born by elective caesarean section at 35+6 weeks’ gestation with a birth weight of 1750g (−2.46 SD), length of 42cm (−2.78 SD) and head circumference (HC) of 28.5cm (−2.64 SD). The following characteristics were observed at birth: small palpebral fissures, epicanthus, microphthalmia, wide nasal root, teletelia, mild axial hypotonia, arachnodactyly, a wider-than-normal gap between the first and second toes (“sandal gap”) in both feet, and two café-au-lait spots in the dorsal region and lower right limb less than 0.5cm in diameter. Central nervous system involvement was suspected, so a transfontanellar ultrasound examination was performed that revealed no malformations. Echocardiographic examination detected a patent foramen ovale, and abdominal ultrasonography a right pelvic kidney. Cytomegalovirus was not detected in the blood or urine. Karyotyping evinced the presence of ring chromosome 2. A 60K oligonucleotide array comparative genomic hybridization (CGH; KayroArray® v3.0, Agilent) found a 6.45Mb deletion in the 2q37.1–2q37.3 region. The parents were healthy and nonconsanguineous, and had normal karyotypes. The physical examination found a weight of 6300kg (−3.55 SD), length of 67cm (−3.55 SD) and HC of 38.4cm (−5.51 SD for age and length). At 12 months of age, the dysmorphic features present at birth remained and were accompanied by a prominent forehead with a low-set hairline, arched eyebrows, a long philtrum, thin upper lip, low-set and rotated ears, prominent antihelix, short neck, 12 café-au-lait spots scattered through the left upper limb, right lower limb and posterior side of the thorax (the largest one 2cm and the rest 0.5cm in diameter), hypoplastic scrotum with presence of both testes, 2mL in volume, and accumulation of fatty tissue in the dorsum of hands and feet (Fig. 1). The patient showed mild psychomotor retardation, predominantly motor, with hypotonia.

Figure 1.

Phenotype of patient with ring chromosome 2. Note the small palpebral fissures, epicanthus, microphthalmia and broad nasal root.

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Chromosome 2 is the second largest human chromosome, accounting for 8% of the genetic material. The ring fusion takes place after the break of the chromosome arms at the telomeric regions, with or without loss of genetic material. Deletions occur most commonly in the 2q37 and 2p25 regions, as they are at the distal ends of the chromosome. Cote et al. defined “ring syndrome” as a set of phenotypic manifestations observed in many patients with different ring chromosomes that were caused by mitotic instability and tissue-specific mosaicim,1 with possible loss of genetic material. The most common clinical manifestations found in patients with ring chromosome 2 are: intrauterine growth restriction, microcephaly, failure to thrive, psychomotor retardation and minor dysmorphic features,2,4 all of which were found in our patient. Cases in which there is loss of genetic material from the 2q37 region may also present with additional phenotypic characteristics, such as brachydactyly, obesity, hypotonia, dysmorphic facial features such as those found in our patient and joint hypermobility, and there is a higher incidence of autism spectrum disorders in these cases. Other and less frequent manifestations include congenital heart malformations such as septal defects or patent ductus arteriosus, congenital hearing loss, tracheomalacia, urogenital malformations, situs anomalies and osteopaenia.5 The phenotypic variability found in these patients suggests that there are various cryptogenic and environmental factors at play in the individual development of the disease.2 The diagnosis is confirmed by genetic testing. The diagnosis was performed prenatally in one case reported in the literature by means of CGH arrays of amniotic fluid samples performed after detection of IUGR and lissencephaly in prenatal ultrasound examination.3 If mosaicism is ruled out in both parents, the recurrence risk is less than 1%. Although changes in fertility have been reported in the literature, especially in males, 50% of the offspring may inherit the ring chromosome, so genetic counselling is recommended.2 These patients require followup by an interdisciplinary team with periodic evaluations.