Ullrich‐Turner syndrome with a small ring X chromosome and presence of mental retardation

Abstract

Since some patients with Ullrich-Turner syndrome (UTS) have mental retardation, we reviewed our experience to look for a high-risk subgroup. Among 190 UTS and gonadal dysgenesis patients with X chromosome abnormalities, 12 had mental retardation. All of the six (100%) with a small ring X were educable (EMI) or trainable mentally impaired (TMI) with more severe delay than expected in UTS. Among the 184 with other X abnormalities, only 6 had similar delays (2 from postnatal catastrophes), for a frequency of 3.3% mental retardation among those without a small ring X; only 2.2% of these had unexplained mental retardation. Polymerase chain reaction studies showed no Y-derived material in the 2 patients who were evaluated, and in situ hybridization confirmed X origin of the ring in the 6 subjects who were evaluated. We describe the phenotype of the 6 individuals with a small ring X, and an additional 2 patients with a small ring X who were identified outside the survey. The subjects with a small ring X comprised a clinically distinct subgroup which had EMI/TMI and shorter stature than expected in UTS. Seizures and a head circumference less than 10th centile were observed in half of the patients with a small ring X, and strabismus, epicanthus, and single palmar creases were present in more than half. A "triangular" face in childhood, pigmentary dysplasia, sacral dimple, and heart defects were also common. Neck webbing appeared to be less frequent than in 45,X. We hypothesize that the high risk of mental retardation in this form of the UTS results from lack of lyonization of the ring X due to loss of the X inactivation center. Excluding those with a small ring X, mental retardation is not significantly increased in patients with UTS.

Laboratory guideline for Turner syndrome

“…Depending on the size and content of the small ring/marker, lack of the XIST locus may be associated with a more severe phenotype that includes mental retardation. 26,31 For interphase analysis using X and Y centromere probes, normal cutoff values should be established for a second X chromosome signal using normal male controls, and for a Y chromosome signal using normal female controls. 25 See section E10 for information on establishment of a normal cut-off value (ACMG Standards and Guidelines, www.acmg.net, 2008).…”

Cytogenetic findings in Serbian patients with Turner’s syndrome stigmata

“…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).…”

Molecular cytogenetic characterization of two Turner syndrome patients with mosaic ring X chromosome

“…Besides these, individuals with r (X) can also present with mental disorders, learning difficulties, autistic spectrum disorders, craniofacial abnormalities, cardiovascular problems, skeletal system problems and dermatological problems in severe conditions [7,18,19,30,45]. Clinical manifestation in these cases are dependent on origin, size, replication timing of the ring chromosome, genes affected by copy number variations, level of mosaicism and status of X inactivation [17].…”