Variable facial features in girls with trisomy X. (a) Epicanthal folds and hypertelorism in 2 year old girl, (b) Hypertelorism in 9 year old girl, (c) Lack of dysmorphic features in a 19 year old girl with trisomy X.
Under 16 Age Xxx Girls
Infants and toddlers are at increased risk for early developmental delays, especially in speech-language development and motor development related to hypotonia. Average age at walking independently is 16.2 months (range 11-22 months), and for first words is 18.5 months (range 12 - 40 months) [2]. Prospective studies comparing girls with trisomy X at 24 months of age to sibling controls show impairments in speech and language development. Expressive language may be more impaired than receptive language, with a pattern described as developmental dyspraxia in some patients. However, other patients show impairments in both expressive and receptive language [28]. Speech and language deficits may continue throughout childhood into adulthood, with higher level language difficulties including problems with language processing, verbal fluency, language comprehension, and pragmatic language in some patients [2,28,29].
Couples should be informed that fetal survival rate is good, with 99% surviving to term following diagnosis after amniocentesis [64,65]. It is not routine to karyotype parents of girls with 47,XXX as recurrence risk is estimated to be
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Mosaic forms of TS tend to have improved prognoses and milder phenotypes. The improved growth and ovarian function of 45,X/46,XX patients over 45,X patients have been well established, and the rarer karyotype 45,X/47,XXX (about 2% of those with TS) also results in more mildly affected girls [10]. The study from Glasgow, Scotland, evaluated the seven 45,X/47,XXX girls registered in the Scottish Turner Syndrome database. Three of the seven subjects did not require growth hormone to achieve a satisfactory height, in comparison to the 45,X and 45,X/46,Xi(X)(q10) matched subjects, all 21 of whom required growth hormone. Additionally, all the 45,X/47,XXX subjects underwent spontaneous puberty, and all five of those older than twelve had spontaneous menarche with regular menstrual cycles. Only 2 of the 14 girls in the 45,X comparison group had spontaneous puberty, and none achieved menarche without the use of estrogen. This is consistent with previous findings [11, 12]. Also, none of the 45,X/47,XXX girls had cardiac or renal abnormalities, though two had middle ear issues. This is in contrast to the 13 of 21 matched subjects with abnormalities to the heart, renal system, or both and is in contrast to the 15 of 21 girls with middle ear issues. The study also had a geneticist, who was blinded to the genotype of the subjects, evaluate for dysmorphic features. 45,X/47,XXX subjects had the most mild expression. Lastly, none of the 45,X/47,XXX subjects had special education needs, in contrast to four in the comparison group. It appears that the haploinsufficiency from the single X chromosome in 45,X is mitigated by the overtranscription of the X chromosome that results from having a 47,XXX cell line [10].
While 45,X/47,XXX girls have milder phenotypes, as discussed previously, the outcome for any individual is unpredictable. In the case of our patient, we saw urinary system malformations and short stature, but no cardiac, middle ear, pubertal, or learning issues. We are seeing the early stages of spontaneous puberty, and she will probably experience spontaneous menarche shortly [10].
Overall, making predictions regarding what the future has in store for these mosaic girls is nebulous. For prenatal diagnosis, parents of 45,X/47,XXX girls should be counseled for the possibility of full Turner symptoms but with optimism for a better outcome. Intellectual impairment is reduced compared to 45,X Turner syndrome, which is an important concern for parents who may be considering selective termination [2]. Future fertility also cannot be guaranteed but can be successful in most 45,X/47,XXX women [18].
Phenotypes of 45,X/47,XXX mosaic girls are unpredictable. Cell counts that provide a ratio of 45,X cells to 47,XXX cells should not be considered to have predictive value, because they vary by tissue. Fortunately phenotypes tend to be milder, but the height may be quite short in a way that is out of proportion to the relative mildness of the remainder of the phenotype. Fortunately short stature can be corrected with growth hormone, so families should be aware that this is a possible requirement for their girls. More research will need to be done in this area to assess impact of growth hormone on 45,X/47,XXX mosaic female with short stature as this has not been well studied. 2ff7e9595c
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