A case of ring chromosome 2 with growth retardation, mild dysmorphism, and microdeletion of 2p detected using FISH.

Case report The subject was born to a 22 year old mother and 30 year old father with no relevant medical history. The mother had two previous miscarriages at 10 and 12 weeks. Her antenatal ultrasound scans in this pregnancy were noted to be abnormal (ventriculomegaly, a two vessel cord, and IUGR). At 34 weeks a repeat ultrasound scan showed reduced liquor volume with no fetal breathing movements. An amniocyte culture was attempted but was unsuccessful. The patient was born by lower segment caesarean section at 35 weeks’ gestation. Her birth weight was 1469 g and her head circumference was 29 cm (both below the 3rd centile). She was noted to be dysmorphic and showed severe IUGR. She required ventilation for respiratory distress syndrome. The dysmorphic features include microcephaly, hypertelorism, a wide, flat nasal bridge, bilateral epicanthic folds, narrow and upward slanting palpebral fissures, arched eyebrows, a long philtrum with a thin upper lip, a short neck, right hemihypertrophy, and positional talipes (fig 1). Audiological and ophthalmological assessments have been normal to date. In addition, she has nine café au lait patches on her skin, a bifid thumb on her left hand, and a high pitched cry. She had multiple muscular ventriculoseptal defects, which were treated conservatively, and at her most recent review had nearly closed. On follow up until 10 months of age, she has been grossly growth retarded despite an adequate nutrition. Her weight and length are well below the 3rd centile and her head circumference is 4 SD below the mean. She remains developmentally delayed, at present able to sit supported, roll from back to front, place objects in her mouth, and babble, consistent with a developmental age of 5 months. CYTOGENETIC STUDIES Cytogenetic analysis of cultured peripheral blood lymphocytes showed a female karyotype with a ring 2 chromosome. The ring 2 appeared to be complete; bands p24 and q36 were clearly visible in conventional G banded preparations (fig 2A). The patient’s karyotype was therefore determined as 46,XX,r(2) (p25q37). A total of 100 G banded metaphases were examined. Of these, 79 cells contained the ring 2, four cells had 45 chromosomes and no ring, and one cell had 47 chromosomes with two ring 2 chromosomes. The remaining 16 cells showed various rearrangements of the ring, including missing or extra bands and rod shaped derivatives. No normal cells were seen. Both parental karyotypes were normal. Fluorescence in situ hybridisation (FISH) studies using probes specific for the subtelomeric region of the long arm of chromosome 2 (210E15 and CEBII) showed no deletion of this region in the ring 2 (fig 2B). No deletion of Figure 1 Clinical photograph of the patient. JMG 2001;38:e32 (http://www.jmgjnl.com/cgi/content/full/38/9/e32) 1 of 3