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Background: The incidence of autoimmune thyroid diseases (ATD) may vary with the beginning of reproductive function, although few reports differentiate the incidence before and during the onset of puberty, examining gender bias. We analyzed onset of ATD in a pediatric population to assess gender differences in onset age, disease subtype, pubertal status, autoimmune co-morbidity, family history and treatment, focusing on the interaction between gender and pubertal stage. Patients and methods: We retrospectively recorded 382 children and adolescents with ATD. In each patient physical examination was considered. The presence of other associated autoimmune diseases (AAD) and familial predisposition was also recorded. Results: Predominant prevalence was noted in females compared to males ( p < 0.001), both in Hashimoto's diseases (HD or HT) and Graves' disease (GD) ( p < 0.001). Mean age at diagnosis showed no significant difference between sexes ( p > 0.05). A higher prevalence in pubertal subjects was noted compared to prepubertal ( p < 0.001, particularly HT in early and GD in late pubertal stage), without sexes difference intra-(prepubertal vs. pubertal) and inter-puberty groups (prepubertal vs. early pubertal vs. late pubertal). Both in HT and in GD, the prevalence of autoimmune associated diseases (AAD) was higher in males compared to females ( p = 0.04), with similar distribution according to the pubertal maturation. The familial predisposition was similarly distributed in both genders ( p > 0.05) and into pubertal stages ( p > 0.05). Conclusions: Females are more prone to develop ATD during puberty, earlier in HT than in GD. The effect of puberty is not different between genders, suggesting the role of additional factors other than hormones. The screening for detection of ATD is recommended in all patients with positive family history and other autoimmune diseases, mostly in males. Considerations of gender in pediatrics could be important to define pathogenic mechanisms of ATD and to help in early diagnosis and clinical management., (Copyright © 2020 Calcaterra, Nappi, Regalbuto, De Silvestri, Incardona, Amariti, Bassanese, Clemente, Vinci, Albertini and Larizza.)

Introduction: Allostatic load (AL) refers to the physiological response associated with the burden of chronic stress. Excessive weight is an important source of physiological stress that promotes a detrimental chronic low-inflammation state. In order to define a correlation between cumulative biological dysregulation and excess weight, we measured AL scores in a pediatric population. Patients and Methods: We enrolled 164 children and adolescents (11.89 ± 3.89). According to their body mass index (BMI) threshold, subjects were classified as normal in the BMI < 75th percentile, overweight in the BMI 75-95th percentile or obese in the BMI >95th percentile. Data based on 16 biomarkers were used to create the AL score. A dichotomous outcome for high AL was defined in those who had more than four dysregulated components. Results: High AL was noted in 88/164 subjects (53.65%), without significant differences between genders ( p = 0.07) or pubertal status ( p = 0.10). Subjects with a high AL, in addition to a higher BMI ( p < 0.001), showed higher WC and WC/HtR ( p < 0.001), triglycerides ( p = 0.002), fasting blood glucose ( p = 0.03), insulin resistance ( p < 0.001), systolic ( p < 0.001) and diastolic blood pressure ( p = 0.001), GGT ( p = 0.01), PCR ( p = 0.01), and calprotectin ( p < 0.01) as well as lower HDL cholesterol ( p = 0.002) than subjects with a low AL. The rate of the cumulative biological dysregulation increased progressively with increases in BMI ( p < 0.001). Conclusions: A high AL was associated with excess weight. AL may be considered a significant factor correlated with increased morbidity in children who are overweight/obese.

Objective: Patients with Turner syndrome (TS) have an unfavorable cardiometabolic profile. Hyperhomocysteinemia is a potential cardiovascular risk factor influenced by genetic and environmental factors, therapies, unbalanced diets and other lifestyle factors. We retrospectively studied the relationship between total plasma homocysteine (Hcy), serum vitamin B12 (B12) and folate concentration in TS patients, taking into account the genetic profile, diet, smoking habits, hormonal therapies and dietary supplements of the subjects., Patients and Methods: We evaluated 50 TS patients (31.5 ± 12.5 years). Medication, including vitamin supplementation, was obtained. Eating habits, cigarette smoking, alcohol and coffee consumption were investigated using phone interviews. Levels of Hcy metabolism parameters were classified by using the relevant cutoff value for an adult population and compared with a reference sample drawn from the general population., Results: Inadequate Hcy and B12 levels were noted, despite vitamin supplementation. Holotranscobalamin (HoloTC) was above the relevant cutoff in the population, and supplemented subjects showed mean levels lower than nonsupplemented subjects (p = 0.005). Dietary supplementation (p = 0.038), lifestyle (coffee consumption, p = 0.01) and hormonal replacement therapy (p = 0.02) are important factors for Hcy metabolism. No genetic influence on Hcy levels was noted. Multivariable regression analysis identified vitamin supplementation (p = 0.045) as the only independent predictor of increased Hcy levels., Conclusion: Cardiovascular risk in TS can be reduced using educational approaches to a healthy lifestyle with dietary guidelines. Besides this, we also recommend measuring HoloTC for the prompt detection of B12 deficiency and to consider hormone replacement therapy in the biochemical assessment of homocysteine in TS., (© 2018 The Author(s) Published by S. Karger AG, Basel.)

Background: To evaluate the relationship between smoking and metabolic parameters in patients affected by type 1 diabetes (T1D)., Patients and Methods: We enrolled 104 children and young adults (50 females and 54 males) with T1D (aged 16.4 ± 8.6 years). The subjects were divided into three groups according to their smoking habits: no smoking (NS), passive smoking (PS), active smoking (AS). The physical examination of the participants included nutritional status assessment by anthropometry and pubertal stage according to Marshall and Tanner as well as blood pressure measurement. In all patients, metabolic blood assays including fasting blood glucose, insulin, total cholesterol, high-density lipoprotein cholesterol, and triglycerides were measured. Insulin resistance was determined by glucose disposal rate (eGDR). Physical activity was also recorded., Results: Significant differences in biochemical and functional parameters among the three groups were demonstrated, in particular for systolic (p = 0.002) and diastolic pressure (p = 0.02) and eGDR (p = 0.039). No differences in daily insulin dose (p = 0.75) and glycated hemoglobin (p = 0.39) were observed. AS group had significantly higher blood pressure (p < 0.05) and lower eGDR (p ≤ 0.001) compared to NS and PS. Significant difference was also detected between PS and NS in systolic and diastolic (p = 0.02) pressure and eGDR (p = 0.01). In a multivariable model adjusted for age, gender, BMI and physical activity, smoking habits did not maintain any independent association with metabolic parameters., Conclusion: This is the first study in a Mediterranean population, looking at tobacco smoke and cardio-metabolic factors in youth with T1D. The relationship between smoking and unfavorable metabolic profile was demonstrated. On the basis of these findings, smoking tobacco should be considered an important modifiable risk factor for young patients with diabetes mellitus, highlighting the need for intensified smoking prevention and cessation programs.

In patients with autoimmune disease, gynecomastia should not be considered as 1 of the first signs of hyperthyroidism, rather it is a breast pathology that can be present even when euthyroidism restoration is achieved. It is unknown whether the autoimmune nature of thyroid disorders or simply the hyperthyroidism effects breast changes.

Background: The aim of our study is to evaluate if in children with highly positive serology and HLA-DQ2/DQ8 (triple test, TT) and only extra-intestinal symptoms, it is possible to omit performing an intestinal biopsy for celiac disease (CD) diagnosis, as suggested by the new European Society for Pediatric Gastroenterology, Hepatology and Nutrition ESPGHAN guidelines., Methods: In this retrospective study a total of 105 patients, suspected of having CD because of extra-intestinal symptoms and showing serum tissue transglutaminase antibody (anti-tTG) and anti-endomysial antibody (EMA) measurements and HLA genotyping, were considered for the final analysis (33 boys and 72 girls; age range 1.5-17.6 years)., Results: Histological findings confirmed diagnosis of CD in 97 (92.4%) patients. Forty-one patients (39%) showed anti-tTG >10 times normal values, positive EMA and positive HLA-DQ2/DQ8 (positive TT). All of them had a diagnosis of CD, therefore there were no false positive cases. Sixty-four patients were negative for the TT. In eight cases, CD was ruled out and these were considered true negative cases. In the remaining 56 negative TT patients, intestinal biopsy confirmed CD diagnosis and they were considered false negatives. Based on these results, specificity for the TT was 100% and sensitivity was 42.3%., Conclusions: On the basis of the present study, diagnosis of CD can be reliably performed without a duodenal biopsy in children with only extra-intestinal symptoms.

Congenital hypothyroidism (CH), the most frequent form of preventable mental retardation, is predicted to have a relevant genetic origin. However, CH is frequently reported to be sporadic and candidate gene variations were found in <10% of the investigated patients. Here, we characterize the involvement of 11 candidate genes through a systematic Next Generation Sequencing (NGS) analysis. The NGS was performed in 177 unrelated CH patients (94 gland-in-situ; 83 dysgenesis) and in 3,538 control subjects. Non-synonymous or splicing rare variants (MAF < 0.01) were accepted, and their functional impact was predicted by a comprehensive bioinformatic approach and co-segregation studies. The frequency of variations in cases and controls was extended to 18 CH-unrelated genes. At least one rare variant was accepted in 103/177 patients. Monogenic recessive forms of the disease were found in five cases, but oligogenic involvement was detected in 39 patients. The 167 variations were found to affect all genes independently of the CH phenotype. These findings were replicated in an independent cohort of additional 145 CH cases. When compared to 3,538 controls, the CH population was significantly enriched with disrupting variants in the candidate genes (P = 5.5 × 10-7), but not with rare variations in CH-unrelated genes. Co-segregation studies of the hypothyroid phenotype with multiple gene variants in several pedigrees confirmed the potential oligogenic origin of CH. The systematic NGS approach reveals the frequent combination of rare variations in morphogenetic or functional candidate genes in CH patients independently of phenotype. The oligogenic origin represents a suitable explanation for the frequent sporadic CH occurrence., (© The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Background: To assess the clinical validity of controlled attenuation parameter (CAP) in the diagnosis of hepatic steatosis in a series of overweight or obese children by using the imperfect gold standard methodology., Methods: Consecutive children referred to our institution for auxological evaluation or obesity or minor elective surgery were prospectively enrolled. Anthropometric and biochemical parameters were recorded. Ultrasound (US) assessment of steatosis was carried out using ultrasound systems. CAP was obtained with the FibroScan 502 Touch device (Echosens, Paris, France). Pearson's or Spearman's rank correlation coefficient were used to test the association between two study variables. Optimal cutoff of CAP for detecting steatosis was 249 dB/m. The diagnostic performance of dichotomized CAP, US, body mass indexes (BMI), fatty liver index (FLI) and hepatic steatosis index (HSI) was analyzed using the imperfect gold standard methodology., Results: Three hundred five pediatric patients were enrolled. The data of both US and CAP were available for 289 children. Steatosis was detected in 50/289 (17.3%) children by US and in 77/289 (26.6%) by CAP. A moderate to good correlation was detected between CAP and BMI (r = 0.53), FLI (r = 0.55) and HSI (r = 0.56). In obese children a moderate to good correlation between CAP and insulin levels (r = 0.54) and HOMA-IR (r = 0.54) was also found. Dichotomized CAP showed a performance of 0.70 (sensitivity, 0.72 [0.64-0.79]; specificity, 0.98 [0.97-0.98], which was better than that of US (performance, 0.37; sensitivity, 0.46 [0.42-0.50]; specificity, 0.91 [0.89-0.92]), BMI (performance, 0.22; sensitivity, 0.75 [0.73-0.77]; specificity, 0.57 [0.55-0.60]) and FLI or HSI., Conclusions: For the evaluation of liver steatosis in children CAP performs better than US, which is the most widely used imaging technique for screening patients with a suspicion of liver steatosis. A cutoff value of CAP of 249 dB/m rules in liver steatosis with a very high specificity.

Aim of the Study: Turmer syndrome (TS) patients show increased morbidity due to metabolic, autoimmune and cardiovascular disorders. A risk of neoplasia is also reported. Here, we review the prevalence of neoplasia in a cohort of Turner patients., Methods: We retrospectively evaluated 87 TS women. Follow-up included periodic ultrasound of the neck, abdominal and pelvic organs, dermatologic evaluation and fecal occult blood test. Karyotype was 45,X in 46 patients. During follow-up, 63 girls were treated with growth hormone, 65 with estro-progestin replacement therapy and 20 with L-thyroxine. Autoimmune diseases were present in 29 TS., Results: A total of 17 neoplasms in 14 out of 87 patients were found. Six skin neoplasia, 3 central nervous system tumors, 3 gonadal neoplasia, 2 breast tumors, 1 hepatocarcinoma, 1 carcinoma of the pancreas and 1 follicular thyroid cancer were detected. Age at tumor diagnosis was higher in 45,X pts than in those with other karyotypes (p = 0.003). Adenomioma gallbladdder (AG) was detected in 15.3% of the patients, with a lower age in girls at diagnosis with an associated neoplasia in comparison with TS without tumors (p = 0.017). No correlation between genetic make up, treatment, associated autoimmune diseases and neoplastia was found., Conclusion: In our TS population an increased neoplasia prevalence was reported. A high prevalence of AG was also noted and it might be indicative of a predisposition to neoplasia. Further studies are needed to define the overall risk for neoplasia, and to determine the role of the loss of the X-chromosome and hormonal therapies., (Copyright © 2016 Elsevier Masson SAS. All rights reserved.)

Postoperative effect of music listening has not been established in pediatric age. Response on postoperative distress and pain in pediatric day care surgery has been evaluated. Forty-two children were enrolled. Patients were randomly assigned to the music-group (music intervention during awakening period) or the non-music group (standard postoperative care). Slow and fast classical music and pauses were recorded and played via ambient speakers. Heart rate, blood pressure, oxygen saturation, glucose and cortisol levels, faces pain scale and Face, Legs, Activity, Cry, Consolability (FLACC) Pain Scale were considered as indicators of response to stress and pain experience. Music during awakening induced lower increase of systolic and diastolic blood pressure levels. The non-music group showed progressive increasing values of glycemia; in music-group the curve of glycemia presented a plateau pattern (P<0.001). Positive impact on reactions to pain was noted using the FLACC scale. Music improves cardiovascular parameters, stress-induced hyperglycemia. Amelioration on pain perception is more evident in older children. Positive effects seems to be achieved by the alternation of fast, slow rhythms and pauses even in pediatric age.

Study Question: What is the burden of X chromosome mosaicism in the occurrence of spontaneous menarche (SM) in Turner syndrome (TS)?, Summary Answer: SM was significantly associated with X chromosome mosaicism in the TS patients; a mosaicism with around 10% euploid cell line may predict spontaneous pubertal development when determined by molecular-cytogenetic techniques on uncultivated tissues., What Is Known Already: Spontaneous puberty can be observed in a minority of patients with TS, more frequently, but not exclusively, in those with a high level of 46,XX/45,X mosaicism at standard karyotype. The genetic mechanisms contributing to ovarian function in TS patients are still not determined. However, submicroscopic X-linked and autosomal copy number variations (CNVs) have recently emerged as an important genetic risk category for premature ovarian insufficiency and may be involved in modulating the TS ovarian phenotype., Study Design, Size, Duration: A group of 40 patients with a diagnosis of TS at conventional karyotyping participated in the study; 6 patients had SM and 34 patients had primary amenorrhoea (PA). All clinical data and the patients' DNA samples were collected over the years at a single paediatric clinic., Participants/materials, Setting, Methods: The patients' samples were used to perform both genetic (Copy Number Assay) and molecular-cytogenetic (array-CGH and iFISH, interphase-FISH) analyses in order to evaluate the X chromosome mosaicism rate and to detect possible rare CNVs of genes with a known or predicted role in female fertility., Main Results and the Role of Chance: All TS patients showed variable percentages of the 46,XX lineage, but these percentages were higher in the SM group (P < 0.01). A mosaicism around 10% for the euploid cell line may predict spontaneous pubertal development when determined by molecular-cytogenetic techniques performed in uncultivated tissues. A few CNVs involving autosomal and X-linked ovary-related loci were identified by array-CGH analysis and confirmed by real-time quantitative PCR, including a BMP15 gene duplication at Xp11.22, a deletion interrupting the PAPPA gene at 9q33.1, and an intragenic duplication involving the PDE8A gene at 15q25.3., Limitations, Reasons for Caution: This is a pilot study on a relatively small sample size and confirmation in larger TS cohorts may be required. The ovarian tissue could not be studied in any patients and in a subgroup of patients, the mosaicism was estimated in tissues of different embryonic origin., Wider Implications of the Findings: The combined determination of X chromosome mosaicism by molecular and molecular-cytogenetic techniques may become useful for the prediction of SM in TS. The detection of CNVs in both X-linked and autosomal ovary-related genes further suggests gene dosage as a relevant mechanism contributing to the ovarian phenotype of TS patients. These CNVs may pinpoint novel candidates relevant to female fertility and generate further insights into the mechanisms contributing to ovarian function., Study Funding/competing Interest(s): This study was funded by Telethon Foundation (grant no: GGP09126 to L.P.), the Italian Ministry of the University and Research (grant number: 2006065999 to P.F.) and a Ministry of Health grant 'Ricerca Corrente' to IRCCS Istituto Auxologico Italiano (grant number: 08C704-2006). The authors have no conflict of interest to declare.

Tubercular spinal localization is very rare (5%) in paediatric age. We report the unusual case of a child with a history of bacillus Calmette-Guerin vaccination who presented with lymphadenitis in the absence of pulmonary involvement. Despite appropriate anti-tubercular therapy, the patient developed spinal tuberculosis with cord compression. Urgent surgical decompression was performed: laminectomy was done at D3-D5 levels and the higher abscess was then flushed using a catheter, decompressing the cauda equina. Our findings suggest that diagnosis of tuberculosis should be considered even in light of anamnestic vaccination at birth, and that surgical treatment should be rapidly provided in the event of spinal cord compression to avoid devastating sequelae.

Ovarian tumors associated with hormonal changes of the peripheral iso-sexual precocious puberty are of common presentation. We describe here a rare case of juvenile granulosa cell tumor in a female with central precocious puberty (CPP). An 8-year old girl with CPP presented with vaginal bleeding four months after the diagnosis and before starting treatment with gonadotropin-releasing hormone (GnRH)-analogs. Suppression of basal follicle-stimulating hormone (FSH) level, elevation of serum estradiol, progesterone and Cancer Antigen-125 were documented. Abdominal ultrasound examination (US) and magnetic resonance imaging showed a pelvic mass affecting the left ovary. A left salpingo-oophorectomy was performed and the mass was totally resected. Juvenile granulosa cell ovarian tumor was diagnosed. One month post surgery, estradiol and progesterone decreased to values of the first evaluation and FSH increased; Cancer Antigen-125 resulted normal while ultrasound pelvic examination showed absence of pelvic masses. In our patient, the tumor had grown very quickly since hormonal data demonstrated a CPP without any evidence of ovarian mass on US only four months before diagnosis. The overstimulation of the FSH or aberrant activation of FSH receptors may have contributed to the development of the mass.

Objective. To describe a biochemical growth hormone (GH) deficiency and to evaluate therapeutic result in a six-year-old male with Becker muscular dystrophy (BMD). Methods. GH peak was evaluated after response to arginine and insulin. Bone age was evaluated according to Greulich and Pyle method. Results. The GH-supplementary therapy was very effective in terms of growth gain. Conclusion. The possibility of a growth hormone deficiency and treatment with GH in patients with BMD cannot be excluded, especially considering the good therapeutic response.

The metabolic syndrome (MetS) is a common basis for the development of atherogenic cardiovascular disease. Adiponectin has been demonstrated to be insulin-sensitizing and an anti-atherogenic factor and is considered a key ofMetS. It was suggested that IL-10 may be involved in the inflammatory network of MetS in relation to adiponectin. We examined the relationship between adiponectin, IL-10 and MetS in pediatric obese patients. MetS components were assessed in 70 severely obese and 30 non-obese children and adolescents. Serum levels of adiponectin and IL-10 were measured in these subjects. Serum adiponectin levels were significantly lower (p < 0.001) and levels of IL-10 were significantly higher (p = 0.012) in obese subjects. MetS was present in 35.71% of obese patients. Patients with MetS showed a borderline significant decrease in serum adiponectin levels and significantly increased IL-10 levels when compared to those without MetS (p = 0.051 and p = 0.031, respectively); the differences in adiponectin and IL-10 values were controlled to the effect of BMI. No correlation between adiponectin and IL-10 levels was found. Our obese children showed hypoadiponectin and hyper-IL10 values. MetS was not associated with low IL-10. We probably observe a first phase of the complex mechanism implicated in the development of the MetS in children.

Objective: Perforin plays a key role in cell-mediated cytotoxicity. Mutations of its gene, PRF1, cause familial hemophagocytic lymphohistiocytosis but have also been associated with lymphomas and the autoimmune/lymphoproliferative syndrome. The aim of this work was to investigate the role of PRF1 variations in type 1 diabetes., Research Design and Methods: We typed for the N252S and A91V variations in an initial population of 352 type 1 diabetic patients and 816 control subjects and a second population of 365 patients and 964 control subjects. Moreover, we sequenced the coding sequence and intron-exons boundaries in 200 patients and 300 control subjects., Results: In both cohorts, allelic frequency of N252S was significantly higher in patients than in control subjects (combined cohorts: 1.5 vs. 0.4%; odds ratio 6.68 [95% CI 1.83-7.48]). Sequencing of the entire coding region detected one novel mutation in one patient, causing a P477A amino acid change not detected in 199 patients and 300 control subjects. Typing for HLA-DQA1 and DQB1 alleles showed that type 1 diabetes-predisposing DQ alpha/DQ beta heterodimers were less frequent in patients carrying N252S or P477A than in those carrying wild-type PRF1. We previously found that natural killer (NK) activity is not decreased in most N252S heterozygotes, but we detected one whose NK activity was normal at the age of 12 but strikingly low in early childhood. Here, we discovered that NK function was low in three heterozygotes in early childhood, one homozygous adult, and in the subject carrying P477A., Conclusions: These data suggest that N252S and possibly other PRF1 variations are susceptibility factors for type 1 diabetes development.

The ADULT syndrome (Acro-Dermato-Ungual-Lacrimal-Tooth, OMIM 103285) is a rare ectodermal dysplasia associated with limb malformations and caused by heterozygous mutations in p63. ADULT syndrome has clinical overlap with other p63 mutation syndromes, such as EEC (OMIM 604292), LMS (OMIM 603543), AEC (106260), RHS (129400) and SHFM4 (605289). ADULT syndrome characteristics are ectrodactyly, ectodermal dysplasia, mammary gland hypoplasia and normal lip and palate. The latter findings allow differentiation from EEC syndrome. LMS differs by milder ectodermal involvement. Here, we report three new unrelated ADULT syndrome families, all with mutations of arginine 298. On basis of 16 patients in five families with R298 mutation, we delineate the ADULT syndrome phenotype. In addition, we have documented a gain-of-function effect on the dNp63gamma isoform caused by this mutation. We discuss the possible relevance of oral squamous cell carcinoma in one patient, who carries this p63 germline mutation.

We investigated whether molecular defects in the CYP21 gene were detectable in two common sex chromosome aberrations, the Turner and the Klinefelter syndromes. We found abnormal 17-hydroxyprogesterone levels after adrenal stimulation in 26/60 (43.3%) patients affected by these chromosome aberrations, as compared with only 11/68 (16.2%) normal controls (P=0.0014, odds ratio 4.0). Screening of the CYP21 gene identified a single Val281Leu missense mutation in exon 7 in 9/63 (14.3%) of the patients, all nine of whom were heterozygote carriers; the mutation frequency was significantly higher than in the general population (P=0.007, odds ratio=3.5). The hormonal and molecular data indicate that these common sex chromosome aberrations are associated with a remarkably high frequency of steroidogenic defects. It may be hypothesised that reduced levels of steroid 21-hydroxylase could confer a survival advantage, leading to a successful pregnancy.

The olfactory receptor (OR)-gene superfamily is the largest in the mammalian genome. Several of the human OR genes appear in clusters with > or = 10 members located on almost all human chromosomes, and some chromosomes contain more than one cluster. We demonstrate, by experimental and in silico data, that unequal crossovers between two OR gene clusters in 8p are responsible for the formation of three recurrent chromosome macrorearrangements and a submicroscopic inversion polymorphism. The first two macrorearrangements are the inverted duplication of 8p, inv dup(8p), which is associated with a distinct phenotype, and a supernumerary marker chromosome, +der(8)(8p23.1pter), which is also a recurrent rearrangement and is associated with minor anomalies. We demonstrate that it is the reciprocal of the inv dup(8p). The third macrorearrangment is a recurrent 8p23 interstitial deletion associated with heart defect. Since inv dup(8p)s originate consistently in maternal meiosis, we investigated the maternal chromosomes 8 in eight mothers of subjects with inv dup(8p) and in the mother of one subject with +der(8), by means of probes included between the two 8p-OR gene clusters. All the mothers were heterozygous for an 8p submicroscopic inversion that was delimited by the 8p-OR gene clusters and was present, in heterozygous state, in 26% of a population of European descent. Thus, inversion heterozygosity may cause susceptibility to unequal recombination, leading to the formation of the inv dup(8p) or to its reciprocal product, the +der(8p). After the Yp inversion polymorphism, which is the preferential background for the PRKX/PRKY translocation in XX males and XY females, the OR-8p inversion is the second genomic polymorphism that confers susceptibility to the formation of common chromosome rearrangements. Accordingly, it may be possible to develop a profile of the individual risk of having progeny with chromosome rearrangements.

We characterized by fluorescence in situ hybridization and Southern blotting 14 partial Xq monosomies, 11 due to terminal deletions and 3 secondary to X/autosome translocations. Three cases were mosaics with a XO cell line. In view of the possible role played by telomeres in chromosome segregation, we hypothesize a relationship between the loss of telomeric sequences in terminal deletions and the presence of 45,X cells. A correlation between phenotype and extent of deletion reveal that there is no correspondence between the size of the deletion and impairment of gonadal function. Turner stigmata are absent in patients without an XO cell line, when the breakpoint is distal to Xq24. A low birthweight is present whenever the breakpoint is at q22 or more proximal.

We report two unrelated women with gonadal dysgenesis, and a (6;15)(p21.3;q15) and a (8;9)(p11.2;q12) balanced translocation, respectively. The patients were of normal stature and showed no phenotypic abnormality or malformation other than ovarian failure. We are not aware of other reports of balanced autosomal translocations associated with gonadal dysgenesis in women. The occurrence of chromosome anomaly and sterility in the two females may be coincidental. However, studies on mouse gametic progression indicate that balanced autosomal translocations can cause oocyte degeneration and reduction of reproductive lifespan. On the basis of these observations, we cannot exclude that the ovarian failure in our patients is the result of oocyte degeneration because of as yet unidentified consequences of the balanced translocations.