Three patients with ring (X) chromosomes and a severe phenotype.

Abstract

Three patients with mosaicism and a cell line containing a small ring (X) chromosome are described. Their phenotype is similar to several previously reported patients with a 45,X/46,X,r(X) karyotype and a phenotype far more severely affected than expected in Turner's syndrome. The clinical picture includes mental retardation, a facial appearance reminiscent of the Kabuki make up syndrome, and limb anomalies. Some of the patients also had streaky hyperpigmentation of the skin in a pattern suggesting dermal mosaicism. It (fig 1).The baby subsequently suffered from recurrent wheezing and chest infections. Her developmental and growth delay persisted. At the age of 33 months her length was 3-4 SD and her weight 2-3 SD below the mean for her age. She died at the age of 35 months.The cytogenetic results have been reported in full by Jacobs et al.1 Briefly the majority of the patient's blood leucocytes had a 45,X constitution, the X being inherited from the father. However, 15 of 200 cells had a ring (X) smaller than a G group chromosome while nine cells had two ring chromosomes, one smaller than a G group and one minute. In situ hybridisation with the X centromere probe pSV2X5 confirmed that both ring chromosomes were derived from X chromosome material, presumably that of the mother. Studies of the replication status of the two ring chromosomes were attempted using a terminal pulse of BrdU, but both rings were found to be too small to give accurate results. CASE 2Case 2 (89-1479) was the second child of a healthy 32 year old mother and 33 year old father. The pregnancy was complicated by polyhydramnios and she was born after spontaneous labour at 37 weeks' gestation, weighing 2950 g. Limb abnormalities were noted at birth. She had a short right arm and the right hand had a thumb and two fingers only, all digits being broad and short. The left arm and hand were normal in size but all the digits were broad and short. The right leg and foot were normal but the left femur was slightly short and the left fibula was absent. There was syndactyly of the lateral three toes. The unequal leg length necessitated a below knee amputation at 8 years.As a baby she fed badly owing to palatal incoordination and had slow weight gain.

Cytogenetic findings in Serbian patients with Turner’s syndrome stigmata

“…The smaller the ring, the greater the deletion is, with closer resemblance to classic 45,X Turner's phenotype (Collins et al, 1994). Some authors felt that the r(X) chromosome patients lacked many of the classic Turner's syndrome features and that the majority are not karyotyped until the age of 11 years, usually because of pubertal failure (Dennis et al, 1993;Collins et al, 1994). Also, others believed that the phenotype is more severely affected than expected in classical Turner's syndrome (Migliori et al, 1991;Van Dyke et al, 1992;Dennis et al, 1993;Cantu et al, 1995).…”

Lack of expression of XIST from a small ring X chromosome containing the XIST locus in a girl with short stature, facial dysmorphism and developmental delay

“…Cytogenetic testing in our patient at different times showed different percentages of ring chromosome, demonstrating the difficulty in predicting levels of mosaicism from single samples of a single tissue. Rare cases where XIST expression has been detected with the more severe phenotype generally associated with an active ring chromosome 12,30,37 may reflect the presence of active ring (X) chromosome at a critical stage in development.…”

Coarctation of the aorta in Kabuki syndrome.

“…Twenty patients aged 10 In the previously reported large series of patients with Kabuki syndrome, the incidence of heart abnormalities was about 30% and no particular defect seemed to predominate.3 4 In the current study of 20 unselected children presenting in genetics clinics (nine in the United Kingdom and one in Canada), 11 (55%) had a cardiac malformation. Five children (25%) had more than one documented cardiac malformation which, in all cases, included an aortic coarctation.…”