Proximal 6q deletion phenotype: findings in de novo interstitial deletion 6g14.1g15

Abstract

The phenotype associated with proximal interstitial 6q deletions has been described (Turleau, et al., 1988; Valtat, et al., 1992; Gershoni-Baruch, etal., 1996; Kumar, et al., 1997). Recurrent proximal interstitial breakpoints 6q11-q25 and terminal deletion breakpoint 6q25 were noted (F. Hecht and B.K. Hecht, 1992), and a distinct proximal deletion syndrome was suggested. In this report, we present a new case of proximal 6q deletion supporting this proposal: Birth weight was 5Ib, 15oz after a 41wk pregnancy of a 19 year-old mother complicated by fetal hydronephrosis and oligohydramnios; a nuchal cord was noted at vaginal delivery. Neonatal problems included respiratory distress, a posterior urethral valve with bilateral hydronephrosis, and inguinal hernias which were later repaired. Delayed development was evident at 6mos, when auditory and ophthalmologic exams and routine karyotype were normal. At age 3yrs, he was evaluated for self-mutilation, temper tantrums, nocturnal hyperactivity, and lack of speech development. On exam, height was 10th, weight 25th, and OFC 50th centile. Facies were notable for a high forehead, short palpebral fissures, broad nose with flat nasal bridge, anteverted nares, mid-face hypoplasia, and thin upper lip. A bifid uvula, prominent and cupped ears, and syndactyly of right 3rd-4th toes were present; sensory and motor exam were normal. Metabolic screening, fragile X DNA, and cranial MRI were normal. A repeat karyotype at 550 bands revealed 46,XY,del(6)(ql4.1q15), and FISH with chromosome 6 painting probe revealed uniform hybridization of only both chromosomes 6, confirming the deleted region was not inserted into another chromosome; both parental karyotypes were normal.Our patient shares several recurring major features of a syndrome associated with other 6q interstitial deletions with proximal breakpoints 6q13q15 and 6q14 or q15q16: mental impairment, typical dysmoiphic facies with short palpebral fissures and thin upper lip, and inguinal hernias. In other reports, umbilical hernias were also typical. In our case, urinary tract anomalies were evident prior to birth, a post-natal finding in other cases. A clinical diagnosis of proximal 6q deletion syndrome should be considered and attention paid to that region in cytogenetic screening when these major features are present in developmentally delayed children with negative fragile X and metabolic studies.