Prevalence, diagnostic features, and medical outcomes of females with Turner syndrome with a trisomy X cell line (45,X/47,XXX): Results from the InsighTS Registry.

Turner syndrome (TS) is defined by partial or complete absence of a sex chromosome. Little is known about the phenotype of individuals with TS mosaic with trisomy X (45,X/47,XXX or 45,X/46,XX/47,XXX) (~3% of TS). We compared the diagnostic, perinatal, medical, and neurodevelopmental comorbidities of mosaic 45,X/47,XXX (n = 35, 9.4%) with nonmosaic 45,X (n = 142) and mosaic 45,X/46,XX (n = 66). Females with 45,X/47,XXX had fewer neonatal concerns and lower prevalence of several TS-related diagnoses compared with 45,X; however the prevalence of neurodevelopmental and psychiatric diagnoses were not different. Compared to females with 45,X/46,XX, the 45,X/47,XXX group was significantly more likely to have structural renal anomalies (18% vs. 3%; p = 0.03). They were twice as likely to have congenital heart disease (32% vs. 15%, p = 0.08) and less likely to experience spontaneous menarche (46% vs. 75% of those over age 10, p = 0.06), although not statistically significant. Congenital anomalies, hypertension, and hearing loss were primarily attributable to a higher proportion of 45,X cells, while preserved ovarian function was most associated with a higher proportion of 46,XX cells. In this large TS cohort, 45,X/47,XXX was more common than previously reported, individuals were phenotypically less affected than those with 45,X, but did have trends for several more TS-related diagnoses than individuals with 45,X/46,XX.

The emotional journey of adapting to prenatally identified trisomy X.

There is a paucity of research on the experiences of parents of children with trisomy X (47,XXX). Increased prenatal diagnoses associated with advances in noninvasive prenatal screening necessitate a better understanding of how trisomy X impacts family systems. This qualitative investigation aimed to describe the lived experience of parents of young daughters with prenatally identified trisomy X to guide genetic counseling. Semi-structured qualitative interviews were conducted via teleconferencing with parents (n = 11) of girls with trisomy X, ages 6-44 months. A descriptive phenomenological approach was used to code transcripts for significant statements and reduce data into themes describing the experience of receiving a diagnosis of trisomy X and the experience of early parenting in this population. Participants described an emotional journey of adapting to prenatally identified trisomy X. Four descriptive themes included two related, yet distinct, life stages: Negative Diagnostic Experience and a Hopeful Early Childhood, as well as two ongoing experiences: Persistent Ambiguity and Coping with and Adapting to Uncertainty. Results suggest providers should carefully consider word choice and timing in delivery of diagnosis, and genetic counseling should provide expectant parents with current research specific to trisomy X, facilitate connections with other parents of young girls with trisomy X, introduce developmental monitoring approaches, and be prepared to support families with a range of emotional responses to the diagnosis and decisions regarding disclosure.

Early symptoms of autism spectrum disorder (ASD) in 1-8 year old children with sex chromosome trisomies (XXX, XXY, XYY), and the predictive value of joint attention.

The objective of the present study is to investigate the impact of Sex Chromosome Trisomy (SCT; XXX, XXY, XYY) on the early appearance of Autism Spectrum Disorder (ASD) symptoms, and the predictive value of Joint Attention for symptoms of ASD. SCTs are specific genetic conditions that may serve as naturalistic 'at risk' models of neurodevelopment, as they are associated with increased risk for neurobehavioral vulnerabilities. A group of 82 children with SCT (aged 1-8 years) was included at baseline of this longitudinal study. Joint Attention was measured at baseline with structured behavior observations according to the Early Social Communication Scales. ASD symptoms were assessed with the Modified Checklist for Autism in Toddlers questionnaire and Autism Diagnostic Interview-Revised in a 1-year follow-up. Recruitment and assessment took place in the Netherlands and in the United States. The results demonstrate that ASD symptoms were substantially higher in children with SCT compared to the general population, with 22% of our cohort at clinical risk for ASD, especially in the domain of social interaction and communication. Second, a predictive value of Joint Attention was found for ASD symptoms at 1-year follow-up. In this cohort, no differences were found between karyotype-subtypes. In conclusion, from a very early age, SCT can be associated with an increased risk for vulnerabilities in adaptive social functioning. These findings show a neurodevelopmental impact of the extra X or Y chromosome on social adaptive development associated with risk for ASD already from early childhood onward. These findings advocate for close monitoring and early (preventive) support, aimed to optimize social development of young children with SCT.

Unusual Trisomy X Phenotype Associated with a Concurrent Heterozygous 16p11.2 Deletion: Importance of an Integral Approach for Proper Diagnosis.

Trisomy X is the most frequent sex chromosome anomaly in women, but it is often underdiagnosed postnatally because most patients do not show any clinical manifestation. It is estimated that only 10% of patients with trisomy X are diagnosed by clinical findings. Thus, it has been proposed that the clinical spectrum is not yet fully delimited, and additional uncommon or atypical clinical manifestations could be related to this entity. The present report describes a female carrying trisomy X but presenting atypical manifestations, including severe intellectual disability, short stature, thymus hypoplasia, and congenital hypothyroidism (CH). These clinical findings were initially attributed to trisomy X. However, chromosome microarray analysis (CMA) subsequently revealed that the patient also bears a heterozygous 304-kb deletion at 16p11.2. This pathogenic copy-number variant (CNV) encompasses 13 genes, including TUFM. Some authors recommend that when a phenotype differs from that described for an identified microdeletion, the presence of pathogenic variants in the non-deleted allele should be considered to assess for an autosomal recessive disorder; thus, we used a panel of 697 genes to rule out a pathogenic variant in the non-deleted TUFM allele. We discuss the possible phenotypic modifications that might be related to an additional CNV in individuals with sex chromosome aneuploidy (SCA), as seen in our patient. The presence of karyotype-demonstrated trisomy X and CMA-identified 16p11.2 deletion highlights the importance of always correlating a patient's clinical phenotype with the results of genetic studies. When the phenotype includes unusual manifestations and/or exhibits discrepancies with that described in the literature, as exemplified by our patient, a more extensive analysis should be undertaken to enable a correct diagnosis that will support proper management, genetic counseling, and medical follow-up.

The comorbidity landscape of 47,XXX syndrome: A nationwide epidemiologic study.

PURPOSE: This study aimed to describe the comorbidity pattern in 47,XXX syndrome. METHODS: This was a registry-based study of hospital diagnoses and prescribed medication in a nationwide cohort of females with 47,XXX (n = 103) and 46,XX/47,XXX (n = 57) in which they were compared with 16,000 age-matched general population female controls. RESULTS: The overall occurrence of hospital diagnoses was significantly increased in females with 47,XXX when compared with controls (incidence rate ratio = 2.1, CI = 1.7-2.5), and when divided into 19 organ-specific groups, there was a significantly increased risk in the following 14 groups: infection, blood, endocrine and metabolism, mental, nervous system, eye, ear, respiratory, oral cavity and gastrointestinal, musculoskeletal, perinatal, congenital malformations, external factors, and "other." The risk of being prescribed any medication was not significantly increased in females with 47,XXX when compared with controls (hazard ratio = 1.2, CI = 0.9-1.4). However, when stratified according to medication groups, a significantly increased risk was detected in 4 of 13 groups. The overall occurrence of hospital diagnoses was also significantly increased when females with 46,XX/47,XXX were compared with controls (incidence risk ratio = 1.3, CI = 1.01-1.8), but generally, in comparison with controls, females with 46,XX/47,XXX were less severely affected than females with 47,XXX. CONCLUSION: The 47,XXX syndrome is associated with an increased occurrence of a wide variety of diseases. Increased awareness of this may contribute to improve counseling and clinical assessment of these patients.

Early impact of X- and Y-chromosome variations (XXX, XXY, XYY) on social communication and social emotional development in 1-2-year-old children.

Sex chromosome trisomies (SCTs) are characterized by an extra X- or Y-chromosome (XXX, XXY, XYY). The present study aims to investigate early signs of social communication and social emotional development in very young children with SCT. Thirty-four children with SCT (aged 12-24 months) were included in this study, as well as 31 age-matched controls. Social communication was measured with structured behavior observations according to the Early Social Communication Scales, and social emotional developmental level with the Bayley Social Emotional parental questionnaire. Recruitment and assessment took place in the Netherlands and in the United States. On average, 12-24-month old children with SCT showed difficulties with early social communication, more so in responding to others as compared to initiating social communications. During social interactions, children with SCT made less frequent eye contact, compared to controls. Also, difficulties in acquiring social emotional milestones were found in 1-year old children with SCT, with 44% of the children having social emotional vulnerabilities in the borderline or extremely low range, compared to typically developing children. In this cohort, no significant predictive effects of karyotype-subtype (XXX, XXY, XYY) were found. Already from a very early age, SCT can be associated with increased risk for vulnerabilities in adaptive social functioning. These findings suggest that SCT impact the maturation of the social brain already from an early age, and stress the importance of early monitoring and (preventive) support early social development in young children with SCT.

Early developmental impact of sex chromosome trisomies on attention deficit-hyperactivity disorder symptomology in young children.

Individuals with sex chromosome trisomies ([SCT], XXX, XXY, and XYY)) are at increased risk for neurodevelopmental problems, given that a significant portion of the sex chromosome genes impact brain functioning. An elevated risk for psychopathology has also been described, including attention deficit-hyperactivity disorder (ADHD). The present study aimed at identifying early markers of ADHD, providing the first investigation of ADHD symptomology in very young children with SCT. The variety, type, and severity of ADHD symptomology in 1-6-year-old children with SCT (n = 104) were compared with population-based controls (n = 101) using the strengths and weaknesses of ADHD symptoms and normal-behavior (SWAN) parent-report questionnaire. ADHD symptomology was significantly more prevalent in SCT and already present from toddlerhood on, compared to controls. ADHD inattention symptoms were significantly increased in all karyotypes (XXX, XXY, and XYY), boys with XYY also showed significantly more hyperactivity/impulsivity symptoms than controls. Inattentiveness was more pronounced with increasing age for SCT, in contrast to controls. Within the SCT group, 24% of the children had significantly elevated ADHD symptoms at a clinical level. Already from an early age on, SCT is associated with a risk for ADHD, suggesting that its neurodevelopmental risk lies anchored in early brain maturation. Studying this genetically vulnerable population allows for the prospective study of risk markers to facilitate early and preventive interventions.

Tectocerebellar dysraphia and occipital encephalocele associated with trisomy X: case report and review of the literature.

INTRODUCTION: Tectocerebellar dysraphia (TCD) is a rare sporadic malformation associated with severe neurodevelopmental morbidity and high infant mortality. The presence of other ciliopathies worsens the prognosis. Joubert syndrome (JS) is a ciliopathy associated with gene mutations, consisting of midbrain and cerebellum malformations, markedly lack fiber decussation at the level of the pontomesencephalic junction. CASE REPORT: We report the case of a child who was born term with occipital encephalocele (OE), diagnosed with TCD and JS spectrum through computed tomography (CT), magnetic resonance (MR), diffuse tensor imaging (DTI), and clinical findings. She had the OE surgically corrected after spontaneous rupture on the second day after delivery. She developed postoperative ventriculitis, meningitis, and hydrocephalus, successfully treated with intravenous antibiotics and cysto-ventriculostomy, cysto-cisternostomy, third ventriculostomy, and choroid plexus coagulation. G-band karyotyping showed 47, XXX, in all analyzed cells (trisomy X). The infant was followed up for 18 months, presenting, so far, a relatively good outcome. CONCLUSION: This is the first case reported in the literature of the association of TCD/OE/JS spectrum (JSS) with trisomy X (XXX).

Early neurodevelopmental and medical profile in children with sex chromosome trisomies: Background for the prospective eXtraordinarY babies study to identify early risk factors and targets for intervention.

Sex chromosome trisomies (SCT), including Klinefelter syndrome/XXY, Trisomy X, and XYY syndrome, occur in 1 of every 500 births. The past decades of research have resulted in a broadening of known associated medical comorbidities as well as advances in psychological research. This review summarizes what is known about early neurodevelopmental, behavioral, and medical manifestations in young children with SCT. We focus on recent research and unanswered questions related to the risk for neurodevelopmental disorders that commonly present in the first years of life and discuss the medical and endocrine manifestations of SCT at this young age. The increasing rate of prenatal SCT diagnoses provides the opportunity to address gaps in the existing literature in a new birth cohort, leading to development of the eXtraordinarY Babies Study. This study aims to better describe and compare the natural history of SCT conditions, identify predictors of positive and negative outcomes in SCT, evaluate developmental and autism screening measures commonly used in primary care practices for the SCT population, and build a rich data set linked to a bank of biological samples for future study. Results from this study and ongoing international research efforts will inform evidence-based care and improve health and neurodevelopmental outcomes.

Adaptive functioning in children and adolescents with Trisomy X: An exploratory analysis.

Identifying the factors related to adaptive functioning will improve the information available to families and providers of females with Trisomy X. Cognitive and behavioral features were assessed in 50 females ages 12.2 ± 3.6 years using the Behavior Assessment System for Children Second Edition (BASC-2) and Wechsler Scales of Intelligence. Executive functioning, social skills, and autistic traits were evaluated in a subset. Adaptive functioning was assessed using the BASC-2 adaptive skills composite score (ASC). Participants were classified as average adaptive skills (ASC T-score > 40) or deficits (ASC T-score < 40). Group comparisons were conducted. Multiple linear regression examined which factors contributed to ASC score. Twenty-eight females (55.6%) had adaptive skills deficits with functional communication being the most commonly affected adaptive domain. The group with ASC in the average range had higher verbal IQ (VIQ) and lower rates of numerous behavioral concerns. Internalizing behavior composite, DSM-IV inattentive symptoms score, and VIQ were significant predictors of ASC. Prenatally diagnosed females comprised over 70% of those with average adaptive skills. In this study, internalizing behaviors, inattentive ADHD symptoms, and VIQ were associated with poorer adaptive functioning. Early interventions targeting internalizing behaviors, attention/executive functioning, and communication skills may improve adaptive skills and deserve further study.

Manifestations of systemic lupus erythematosus in female patients with polysomy X: Possible roles of chromosome X.

Clinical manifestations of systemic lupus erythematosus (SLE) in female patients with polysomy X have been less characterized as compared to those in male patients. Here, we describe a 28-year-old woman with trisomy X (47,XXX) who developed SLE. She had polyarthritis, hemolytic anemia, and was positive for anti-nuclear and anti-dsDNA antibodies. We discuss the common SLE manifestations with female polysomy X and the possible link between the development of SLE and the presence of extra X-chromosomes.

Novel biallelic ATM mutations coexist with a mosaic form of triple X syndrome in an 11-year-old girl at remission after T cell acute leukemia.

Ataxia-telangiectasia (AT) is a rare neurodegenerative disease characterized by an early onset ataxia, oculocutaneous telangiectasia, immunodeficiency, recurrent infections, radio-sensitivity, and a predisposition to malignancy. We present the case of a child with coexistent AT and trisomy X (47,XXX). We used fluorescent in situ hybridization (FISH) to confirm that this person had 47,XXX karyotype in blood cells, bone marrow, fibroblasts, and buccal smear. Standard cytogenetic studies (not banded) were conducted on blood cells. G-banding analysis was performed on bone marrow cells at the time of the leukemia diagnosis. Flow cytometric investigation of lymphocytes and Sanger sequencing of the ATM gene were used for diagnosis confirmation and description. We report the case of an 11-year-old girl at remission after having T cell acute leukemia for 7 years with progressive signs of ataxia-telangiectasia and with additional X chromosome since birth. At the age of 2 years and 7 months, she was diagnosed with pre-T acute leukemia. From the age of four, she had gait abnormalities. AT was established at the age of seven based on clinical signs and laboratory findings (increased alpha fetoprotein-AFP [227]) and confirmed by detecting compound heterozygous truncating mutations in the ATM gene (p.Y705X and p.L2312I). These genetic findings have not been previously reported in AT and our "double hit" case demonstrates the value of careful clinical evaluation of children with an established genetic diagnosis. Measurement of AFP levels should be considered in patients with neurologic abnormalities after leukemia treatment.

Phonemic and Semantic Verbal Fluency in Sex Chromosome Aneuploidy: Contrasting the Effects of Supernumerary X versus Y Chromosomes on Performance.

OBJECTIVES: Past research suggests that youth with sex chromosome aneuploidies (SCAs) present with verbal fluency deficits. However, most studies have focused on sex chromosome trisomies. Far less is known about sex chromosome tetrasomies and pentasomies. Thus, the current research sought to characterize verbal fluency performance among youth with sex chromosome trisomies, tetrasomies, and pentasomies by contrasting how performance varies as a function of extra X number and X versus Y status. METHODS: Participants included 79 youth with SCAs and 42 typically developing controls matched on age, maternal education, and racial/ethnic background. Participants completed the phonemic and semantic conditions of a verbal fluency task and an abbreviated intelligence test. RESULTS: Both supernumerary X and Y chromosomes were associated with verbal fluency deficits relative to controls. These impairments increased as a function of the number of extra X chromosomes, and the pattern of impairments on phonemic and semantic fluency differed for those with a supernumerary X versus Y chromosome. Whereas one supernumerary Y chromosome was associated with similar performance across fluency conditions, one supernumerary X chromosome was associated with relatively stronger semantic than phonemic fluency skills. CONCLUSIONS: Verbal fluency skills in youth with supernumerary X and Y chromosomes are impaired relative to controls. However, the degree of impairment varies across groups and task condition. Further research into the cognitive underpinnings of verbal fluency in youth with SCAs may provide insights into their verbal fluency deficits and help guide future treatments. (JINS, 2018, 24, 917-927).

Controlled ovarian stimulation and IVF pregnancy in a trisomy X carrier with associated hypogonadotropic hypogonadism.

We describe successful controlled ovarian stimulation (COS) and the first known IVF pregnancy in a trisomy X carrier with associated hypogonadotropic hypogonadism (HH) linked to a chromosome 4 double mutation in the allele of the Gonadotropins Releasing Hormone receptor (GnRHr) gene. Previous administration of low dose of gonadotropins, as recommended in patients with HH, led to poor follicular recruitment. Since trisomy X is a risk factor for diminished ovarian reserve (DOR) and premature ovarian insufficiency (POI), higher doses of gonadotropins led to better ovarian response. The report readknowledges the importance of a correct genetic evaluation in a competent laboratory as a reliable base for treatment planning in this kind of patients.

Expanding the phenotype of Triple X syndrome: A comparison of prenatal versus postnatal diagnosis.

Triple X syndrome (47, XXX) occurs in approximately 1:1,000 female births and has a variable phenotype of physical and psychological features. Prenatal diagnosis rates of 47, XXX are increasing due to non-invasive prenatal genetic testing. Previous studies suggest that prenatal diagnosed females have better neurodevelopmental outcomes. This cross-sectional study describes diagnosis, physical features, medical problems, and neurodevelopmental features in a large cohort of females with 47, XXX. Evaluation included review of medical and developmental history, physical exam, cognitive, and adaptive testing. Medical and developmental features were compared between the prenatal and postnatal diagnosis groups using rate calculations and Fisher's exact test. Cognitive and adaptive tests scores were compared using t-tests. Seventy-four females age 6 months-24 years (mean 8.3 years) participated. Forty-four (59.5%) females were in the prenatal diagnosis group. Mean age of postnatal diagnosis was 5.9 years; developmental delay was the most common indication for postnatal genetic testing. Common physical features included hypertelorism, epicanthal folds, clinodactyly, and hypotonia. Medical problems included dental disorders (44.4%), seizure disorders (16.2%), genitourinary malformations (12.2%). The prenatal diagnosis group had higher verbal (P < 0.001), general ability index (P = 0.004), and adaptive functioning scores (P < 0.001). Rates of ADHD (52.2% vs. 45.5%, P = 0.77) and learning disabilities (39.1% vs. 36.3%, P = 1.00) were similar between the two groups. These findings expand on the phenotypic features in females with Triple X syndrome and support that prenatally ascertained females have better cognitive and functional outcomes. However, prenatally diagnosed females are still at risk for neurodevelopmental disorders. Genetic counseling and treatment recommendations are summarized. © 2016 Wiley Periodicals, Inc.

Hypogonadotropic hypogonadism in a trisomy X carrier: phenotype description and genotype correlation.

We report on a 31-year old female who presented at genetic counseling for a small uterus, secondary amenorrhea and sterility. Gonadotropic hormone levels were low, suggesting a Hypogonadotropic Hypogonadism (HH) condition. Cytogenetic analysis demonstrated the presence of Trisomy X associated to an interstitial deletion of chromosome 4q13.2, resulting in the complete loss of a copy of the GNRHR gene. As GNRHR is known to be responsible for an autosomal recessive form of HH, we checked the status of the undeleted allele and we found the Q106R substitution. In conclusion, the results of our cytogenetic and molecular analyses have allowed us to clarify the etiology of the patient's condition.

Development of mixed connective tissue disease and Sjögren's syndrome in a patient with trisomy X.

Increased risk of developing systemic lupus erythematosus (SLE) has been reported in patients with Klinefelter syndrome. Here, we describe a 16-year-old Japanese patient with trisomy X (47,XXX) who developed mixed connective tissue disease (MCTD) and Sjögren's syndrome. She had polyarthritis, edematous fingers with Raynaud's phenomenon, sicca syndrome, interstitial lung disease, possible myositis, and was positive for anti-nuclear antibody, anti-nRNP antibody and rheumatoid factor. This is the first report in the literature of a case of MCTD with female polysomy X, which further supports the link between the presence of extra X chromosome(s) and the development of autoimmune diseases.

Bladder exstrophy-epispadias complex and triple-X syndrome: incidental finding or causality?

BACKGROUND: Bladder exstrophy is a rare malformation. Prenatal diagnosis is usually an incidental finding on routine ultrasound examination. Triple-X syndrome (karyotype 47,XXX) is the most frequent sex chromosome aneuploidy in live-born females (approximately 1 in 1000). The diagnosis is often not made because women with 47,XXX karyotype have no or hardly any clinical symptoms during life. METHODS: Prenatal diagnosis of triple X karyotype is usually an incidental finding when an invasive prenatal diagnosis is performed for other reasons. RESULTS: Here, we report on two cases with bladder exstrophy and triple-X syndrome, one in a fetus and one in an adult. In view of two previous reports of this association in literature, causality of these two conditions should be considered. CONCLUSION: A gene dosage effect as possible underlying mechanisms will be discussed.

Research Priorities of Individuals and Families with Sex Chromosome Aneuploidies.

Sex chromosome aneuploidies (SCAs) are chromosomal variations that result from an atypical number of X and/or Y chromosomes. Combined, SCAs affect ~1/400 live births, including individuals with Klinefelter syndrome (47,XXY), Turner syndrome (45,X and variants), Double Y syndrome (47,XYY), Trisomy X (47,XXX), and rarer tetrasomies and pentasomies. Individuals with SCAs experience a wide variety of physical health, mental health, and healthcare experiences that differ from the standard population. To understand the priorities of the SCA community we surveyed participants in two large SCA registries, the Inspiring New Science in Guiding Healthcare in Turner Syndrome (INSIGHTS) Registry and the Generating Advancements in Longitudinal Analysis in X and Y Variations (GALAXY) Registry. 303/629 (48.1% response rate) individuals from 13 sites across the United States responded to the survey, including 251 caregivers and 52 self-advocates, with a range of ages from 3 weeks to 73 years old and represented SCAs including Turner syndrome, XXX, XXY, XYY, XXYY, and combined rare tetrasomies and pentasomies. Results demonstrate the priorities for physical health and emotional/behavioral health identified by the SCA community, as well as preferred types of research. All SCA subtypes indicated intervention studies as the top priority, emphasizing the need for researchers to focus on clinical treatments in response to priorities of the SCA community.

A mathematical framework for genetic relatedness analysis involving X chromosome aneuploidies.

The unique features of the X chromosome can be crucial to complement autosomal profiling or to disentangle complex kinship problems, providing in some cases a similar or even greater power than autosomes in paternity/maternity investigations. While theoretical and informatics approaches for pairwise X-linked kinship analyses are well established for euploid individuals, these are still lacking for individuals with an X chromosome aneuploidy. To trigger the fulfilment of this gap, this research presents a mathematical framework that enables the quantification of DNA evidence in pairwise kinship analyses, involving two non-inbred individuals, one of whom with a non-mosaic X chromosome aneuploidy: Trisomy X (47, XXX), Klinefelter (47, XXY) or Turner (45, X0) syndrome. As previously developed for a regular number of chromosomes, this approach relies on the probability of related individuals sharing identical-by-descent (IBD) alleles at one specific locus and it can be applied to any set of independently transmitted markers, with no gametic association in the population. The kinship hypotheses mostly considered in forensic casework are specifically addressed in this work, but the reasoning and procedure can be applied to virtually any pairwise kinship problem under the referred assumptions. Algebraic formulae for joint genotypic probabilities cover all the possible genotypic configurations and pedigrees. Compared with the analyses assuming individuals with a regular number of chromosomes, complicating factors rely on the different possibilities for both the parental origin of the error (either maternal or paternal), and the type of error occurred (either meiotic or post-zygotic mitotic). These imply that a non-inbred female with Triple X or a male with Klinefelter syndrome may carry two IBD alleles at the same locus. Thus, and contrarily to what occurs for the standard case, IBD partitions depend not only on the kinship hypothesis under analysis but also on the genotypic configuration of the analyzed individuals. For some cases, parameters of interest can be inferred, while for others recommended values based on the available literature are provided. This work is the starting point to analyze X-chromosomal data under the scope of kinship problems, involving individuals with aneuploidies, as it will enhance the quantification of the DNA evidence not only in forensics but also in the medical genetics field. We hope it will trigger the development of approaches including other complicating factors, as a greater number of individuals, possibility of the occurrence of mutations and/or silent alleles, as well as the analysis of linked markers.