Mosaic Syndrome Research Articles

The vein of Galen aneurysmal malformation associated with Turner syndrome mosaicism -a case report

The vein of Galen aneurysmal malformation associated with Turner syndrome mosaicism -a case report

Mosaic Form of Turner Syndrome

Objective: To report a case of breast growth disorder in a mosaic form of Turner Syndrome. Turner syndrome is a chromosomal condition characterized by small height and primary ovarian insufficiency that affects one in every 2500 female births. Mosaicism is likely to occur when monosomy X develops in only a few cells during development. The clinical presentation of Turner syndrome mosaicism is atypical, with symptom severity varying based on the number of affected cells. This case discusses issues with secondary sex development, including mild hyperandrogenism, and explores how combination hormonal treatment can aid in enhancing secondary sex development.
 Method: Case Report.
 Case: A 21-year-old woman presented with chief complaint of the lack of breast enlargement. She exhibited normal genitalia internally and externally and had a regular menstrual cycle. Karyotyping revealed a mosaic pattern of 45, X/46, XX (1 percent/99%) with normal estradiol levels and elevated testosterone levels (indicating mild hyperandrogenism). The patient underwent two cycles of hormone therapy using Ethinyl Estradiol and Drospirenone, resulting in breast growth progression from Tanner stage 1 to Tanner stage 2.
 Conclusion: Mosaicism in Turner syndrome is plausible, and the severity of clinical symptoms correlates with the number of defective chromosomes. The presentation of Turner syndrome mosaicism varies, and therapy should be tailored to address specific symptoms. While breast development is observed in some girls with Turner Syndrome, instances of breast growth disorder may occur, involving estrogen activity and estrogen receptor sensitivity. Although the exact cause of impaired breast growth remains unknown, administering estrogen in such cases can improve secondary sexual characteristics.
 Keywords: mild hyperandrogenism, mosaicism, turner syndrome

Oocyte cryopreservation in mosaic Turner syndrome with polycystic ovaries

To report a case of a patient with Turner syndrome (TS) mosaicism and polycystic ovarian syndrome (PCOS), who underwent successful ovarian stimulation, oocyte retrieval, and cryopreservation. Case report. A female patient with mosaic TS (45,X [24%]/46,XX [76%]) and a paternally inherited balanced reciprocal translocation t(2:6) diagnosed with PCOS. Controlled ovarian stimulation, oocyte retrieval, and cryopreservation. Successful oocyte retrieval and cryopreservation. We report an interesting case of a patient with TS mosaicism 45,X [24%]/46,XX [76%] and a paternally inherited t(2:6) balanced reciprocal translocation, who was diagnosed with PCOS on the basis of oligomenorrhea and ultrasound polycystic ovary morphology (antral follicle count of 17 and >20, left and right ovaries, respectively), underwent 2 cycles of ovarian stimulation, oocyte retrieval, and cryopreservation, resulting in 19 cryopreserved oocytes. Our case highlights the importance of early counseling regarding fertility options in patients with mosaic TS and the need for careful monitoring of ovarian reserve during this process, which could be done by measuring the anti-müllerian hormone or antral follicle count. It also underscores the possibility of women with mosaic TS being affected by PCOS.

Sex chromosome aneuploidies and fertility: 47,XXY, 47,XYY, 47,XXX, and 45,X/47,XXX.

The overall incidence of sex chromosome aneuploidies is approximately 1 per 500 live-born infants, but far more common at conception. I shall review the fertility aspects of the sex chromosome trisomies, XXY, XYY, XXX, with special reference to the karyotype 45,X/47,XXX. Each has a "specific" (but variable) phenotype, but may be modified by mosaicism. Although the alterations in the hypothalamic-pituitary-gonadal axis are important (and discussed), the emphasis is on potential fertility. The reproductive axis is often affected in females with the 47,XXX karyotype with diminished ovarian reserve and accelerated loss of ovarian function. Fewer than 5 % of females with the Turner syndrome have the 45,X/47,XXX karyotype. They have taller stature and less severe fertility issues compared to females with the 45,X or other forms of Turner syndrome mosaicism. For the 47,XXY karyotype non-obstructive azoospermia is almost universal with sperm retrieval by micro-testicular sperm extraction possible in slightly fewer than half of the men. Men with the 47,XYY karyotype have normal to large testes and much less testicular dysfunction than those with the 47,XXY karyotype. They do have a slight increase in infertility compared to the reference population, but not nearly so severe as those with 47,XXY karyotype. Assisted reproductive technology, especially micro-TESE has an important role, especially for those with 47,XXY; however, more recent data show promising techniques for the in vitro maturation of spermatogonial stem cells and 3-D organoids in culture. Assisted reproductive technology is more complex for the female, but vitrification of oocytes has shown promising advances.

An unusual association of type II Mayer-Rokitansky-Kuster-Hauser syndrome, turner mosaic syndrome and tubo-ovarian inguinal hernia– case report and review of literature

BackgroundHerniation of ovaries and Mullerian structures into inguinal canal is usually reported in infants and is rare among adults. We are presenting a rare case of Mullerian agenesis and Turner mosaic syndrome with tubo-ovarian inguinal hernia.Case presentationA 17-year-old girl presented with complaints of primary amenorrhea, phenotypical features of Turner syndrome with left inguinal hernia and severe hypertension. Baseline hormonal analysis was normal. Karyotype revealed Turner mosaic with 46XX (85%); 45XO (15%). MRI showed Mullerian agenesis with normally located right ovary in pelvis and left ovary prolapsed through deep inguinal ring into the canal of Nuck. Anti-hypertensives were started and patient optimized for surgery. Laparoscopic hernia repair and repositioning of left ovary into the pelvis was done. Patient had uneventful post-operative course and was discharged in stable condition on anti-hypertensive medication. Future reproductive issues and need of passive vaginal dilatation or vaginoplasty before marriage were explained to the patient and family.ConclusionThis is the first ever reported case with unusual association of atypical MRKH, Turner mosaic syndrome and tubo-ovarian hernia into the inguinal canal. The case emphasizes the need and importance of complete work up of these atypical cases as patients may have more than one cause of primary amenorrhea and complete evaluation is must before any medical or surgical intervention.

A Comprehensive and Clinical Review of Chromosome 14 Mosaic Trisomy Syndrome

Chromosome 14 mosaic trisomy syndrome is a rare chromosomal disorder in which chromosome number 14 appears three times (trisomy) instead of twice in some cells of the body. Symptoms and physical findings associated with chromosome 14, Trisomy Mosaic may depend on the percentage of cells containing an extra chromosome 14. Trisomy mosaic syndrome of chromosome 14 may also be characterized by abnormal prenatal growth retardation (prenatal growth retardation) and failure to grow and gain weight at an expected rate (growth spurt) in infancy.

8995 Laparoscopic Hernia Repair in a Patient with Mayer-Rokitansky-Kuster-Hauser Syndrome, Turner Mosaic Syndrome and Tubo-Ovarian Hernia

<h3>Study Objective</h3> To report a rare case of Mullerian agenesis and Turner mosaic syndrome with tubo-ovarian inguinal hernia <h3>Design</h3> Case report. <h3>Setting</h3> Department of Obstetrics & Gynecology of a tertiary care referral center. <h3>Patients or Participants</h3> A 17-year-old girl presented with complaints of primary amenorrhea, phenotypical features of Turner syndrome with left inguinal hernia and severe hypertension. <h3>Interventions</h3> Baseline hormonal analysis was normal. Karyotype revealed Turner mosaic with 46XX (85%); 45XO (15%). MRI showed Mullerian agenesis with normally located right ovary in pelvis and left ovary prolapsed through deep inguinal ring into the canal of Nuck. Anti-hypertensives were started, and patient optimized for surgery. Laparoscopic hernia repair and repositioning of left ovary into the pelvis was done. <h3>Measurements and Main Results</h3> Patient had uneventful post-operative course and was discharged in stable condition on anti-hypertensive medication. Future reproductive issues and need of passive vaginal dilatation or vaginoplasty before marriage were explained to the patient and family. <h3>Conclusion</h3> This is the first ever reported case with unusual association of atypical MRKH, Turner mosaic syndrome and tubo-ovarian hernia into the inguinal canal.

Pathogenic TP53 variant allele frequency across different somatic tissues in two patients with mosaic Li-Fraumeni.

10582 Background: The integration of germline genetic testing, frequently from blood, into routine oncological care has increased the frequency at which pathogenic TP53 mutations are found in a variant allele frequency (VAF) range suggestive of either mosaic Li-Fraumeni Syndrome or clonal hematopoiesis of indeterminate potential (CHIP). Mosaic LFS is a rare and poorly described phenomenon wherein a pathogenic TP53 mutation is dispersed in low levels through multiple somatic tissues after stochastically developing during early embryogenesis. In comparison, CHIP is restricted to the bone marrow niche. Germline mosaicism in Li-Fraumeni Syndrome (LFS) is inferred when genomic DNA from a second source recapitulates the exact same TP53 mutation. Given the challenges with sample acquisition, mosaicism has not been previously described in depth in the medical literature. Methods: Two pediatric patients with LFS-associated cancers (glioblastoma, osteosarcoma &amp; ALL respectively) underwent clinical genetics evaluation and were found to have pathogenic TP53 mutations. Initial genetic testing was performed in a CLIA/CAP environment through a send out test or internally. A broad array of somatic tissues was collected at autopsy with subsequent DNA isolation and amplicon sequencing in triplicate to determine the mean VAF of the pathogenic TP53 allele. Results: For both patients, the initial germline test suggesting mosaic LFS had a VAF between 20-30%. Confirmatory intent fibroblast culture in Patient 1 was reported as negative by an external clinical lab and Patient 2’s VAF was much lower. The VAFs for the rest of the somatic tissues as well as in their corresponding cancers are reported below (Table) as means and standard error of the triplicate. Despite the negative fibroblast culture, Patient 1 did demonstrate mutant TP53 in other tissues, confirming mosaicism. Conclusions: The proportion of pathogenic alleles is highly heterogeneous amongst different somatic tissues in mosaic LFS patients. Although CHIP exclusion through germline testing of cultured skin fibroblasts is common, our patients’ skin samples were amongst the tissues with the lowest VAFs. Mosaicism should be highly suspected when tumor sequencing demonstrates an identical mutation to the putative germline mosaic one even with equivocal fibroblast culture results. [Table: see text]

Klinefelter syndrome mosaicism in boys with neurodevelopmental disorders: a cohort study and an extension of the hypothesis

BackgroundKlinefelter syndrome is a common chromosomal (aneuploidy) disorder associated with an extra X chromosome in males. Regardless of numerous studies dedicated to somatic gonosomal mosaicism, Klinefelter syndrome mosaicism (KSM) has not been systematically addressed in clinical cohorts. Here, we report on the evaluation of KSM in a large cohort of boys with neurodevelopmental disorders. Furthermore, these data have been used for an extension of the hypothesis, which we have recently proposed in a report on Turner’s syndrome mosaicism in girls with neurodevelopmental disorders.ResultsKlinefelter syndrome-associated karyotypes were revealed in 49 (1.1%) of 4535 boys. Twenty one boys (0.5%) were non-mosaic 47,XXY individuals. KSM was found in 28 cases (0.6%) and manifested as mosaic aneuploidy (50,XXXXXY; 49,XXXXY; 48,XXXY; 48,XXYY; 47,XXY; and 45,X were detected in addition to 47,XXY/46,XY) and mosaic supernumerary marker chromosomes derived from chromosome X (ring chromosomes X and rearranged chromosomes X). It is noteworthy that KSM was concomitant with Rett-syndrome-like phenotypes caused by MECP2 mutations in 5 boys (0.1%).ConclusionOur study provides data on the occurrence of KSM in neurodevelopmental disorders among males. Accordingly, it is proposed that KSM may be a possible element of pathogenic cascades in psychiatric and neurodegenerative diseases. These observations allowed us to extend the hypothesis proposed in our previous report on the contribution of somatic gonosomal mosaicism (Turner’s syndrome mosaicism) to the etiology of neurodevelopmental disorders. Thus, it seems to be important to monitor KSM (a possible risk factor or a biomarker for adult-onset multifactorial brain diseases) and analysis of neuromarkers for aging in individuals with Klinefelter syndrome. Cases of two or more supernumerary chromosomes X were all associated with KSM. Finally, Rett syndrome-like phenotypes associated with KSM appear to be more common in males with neurodevelopmental disorders than previously recognized.

Turner syndrome mosaicism: Challenges in identification and management in primary care.

The spectrum of Turner syndrome (TS) includes Turner syndrome mosaicism (TSM), which is typically a nonhereditary chromosomal abnormality. Turner syndrome mosaicism presents uncommonly to primary care providers (PCPs), who often fail to recognize the subtle signs. The average age at diagnosis for common TS and TSM karyotype is 5.4 years, averaging 7.3 years. Often genetic confirmation, management, and recommended surveillance are delayed. Oftentimes, the PCP suspects a genetic etiology of an unusual phenotype, such as pinna placement or other unusual ear configurations, webbed neck with low posterior hairline, wide-spaced nipples, or short stature among other presentations. The PCP or geneticist orders diagnostic studies to confirm the diagnosis, such as a karyotype. After diagnosis, the PCP refers to the geneticist who initiates surveillance and makes recommendations for management. There are potential neurocognitive, cardiovascular, renal, reproductive, and endocrine issues. Treatment literature is vague and parental concerns are linked to quality mental health and quality of life for the family member with TS or TSM. The purpose of this article was to use a case study to introduce the topic of TS and TSM and to assist the PCP in the identification and management of patient and family concerns.

Retinoblastoma and mosaic 13q deletion: a case report

BackgroundPatients with 13q-syndrome are at risk of retinoblastoma when the RB1 gene, located in the chromosomal band 13q14.2, is deleted. This syndrome is frequently associated with congenital malformations and developmental delay, although these signs could be mild. Mosaic 13q-deletion patients have been previously reported in the literature; their phenotype is variable, and they may not be recognized.Case presentationRetinoblastoma diagnosed in a child with 13q-mosaicism confirmed in blood, oral mucosa, healthy retina and retinoblastoma. A second RB1 hit is present exclusively in the retinoblastoma sample (RB1 c.958C>T p.Arg320Ter). Other detected molecular events in retinoblastoma are 6p12.3pter gain and 6q25.3qter loss. Clinical examination is unremarkable except for clinodactyly of the right fifth finger.Discussion and conclusionsWe describe a case of mosaic 13q deletion syndrome affected by retinoblastoma. Molecular data obtained from the tumor analysis are similar to previous data available about this malignancy. High clinical suspicion is essential for an adequate diagnosis of mosaic cases.

P–462 First live birth after fertility preservation using vitrified oocytes in a woman with mosaic Turner syndrome

Abstract Study question Is oocyte vitrification an option for preserving the fertility of women diagnosed with Turner syndrome (TS)? Summary answer We report the first live birth achieved using cryopreserved oocytes in a woman diagnosed with mosaic Turner syndrome. What is known already Women with TS are at extremely high risk for premature ovarian insufficiency (POI) and infertility. Although the desire of becoming parents may be fulfilled through egg donation or adoption, fertility preservation using ovarian tissue cryopreservation or oocyte vitrification has been offered to adolescents with TS before complete exhaustion of their follicular stockpile. However, women with TS exhibit higher rates of pregnancy loss and obstetric complications, and the feasibility of fertility preservation in TS is hampered by the reduced follicular pool and by concerns about the X chromosomal content of oocytes and follicular cells. Study design, size, duration Case report in a university hospital. Participants/materials, setting, methods A 25-year-old woman with Turner syndrome mosaicism (45,X0[14]/46,XX[86]) was referred for fertility preservation (FP) counseling. Serum antimüllerian hormone (AMH) level was normal (6.4 µg/L). In view of parenthood postponement and because of the unpredictable rate of follicle loss, the woman underwent two cycles of ovarian stimulation using recombinant follicle stimulating hormone (rFSH), 200–250 IU/day for 8 resp. 12 days, in a GnRH antagonist protocol. Main results and the role of chance In total, 29 metaphase II oocytes (MII) were vitrified. Five years later, the patient returned to the clinic with a desire for pregnancy. Because of evidence of considerable AMH decline (–56% in an interval of four years), the patient was advised to utilize her cryopreserved oocytes for in-vitro fertilization with preimplantation genetic testing for aneuploidy screening (PGT-A). All 29 MII oocytes were thawed; 26 oocytes survived (89.7%) and were inseminated using intracytoplasmic sperm injection (ICSI). Thirteen oocytes were fertilized normally. Three good quality blastocysts ensued and were vitrified after trophectoderm biopsy for PGT-A using array-CGH. Two blastocysts were found euploid. One was thawed and transferred into the uterus using a HRT priming protocol. An uneventful pregnancy occurred. The patient delivered a healthy baby girl weighing 3490 g at 40 weeks of gestation. Limitations, reasons for caution Cryopreservation of oocytes and/or ovarian tissue in selected postmenarchal girls or young women with Turner syndrome is an investigational FP approach that may result in genetic parenthood. The feasibility of FP in TS individuals is limited to those with evidence of ovarian function, before POI occurs. Wider implications of the findings: Cryopreservation of mature oocytes after ovarian stimulation is a realistic option for FP in selected postmenarchal individuals with mosaic TS. Whether PGT-A may reduce the risk of pregnancy loss in TS has to be confirmed by further studies. Trial registration number Not applicable

Andrological and cytogenetic investigations of an infertile Przewalski's stallion.

The case of an 8-year-old, sexually active but infertile Przewalski's stallion (Equus ferus przewalskii) was studied. Besides the infertility, the stallion also showed permanent problems with its body condition, being obviously weaker than all the other group members. The horse was kept in a separate place for two years with 12 mares in its harem group (six mares had foals earlier); however, none of the mares covered got pregnant. Andrological and cytogenetic investigations revealed underdeveloped testes, arrested spermatogenesis, azoospermia, and XY/XXY/X0 mosaicism. We classify the case as a mosaic Klinefelter syndrome, the first reported case in Przewalski's horse.

A rare cause of progressive gait abnormality in a case of Turner syndrome

Turner syndrome is a commonly encountered chromosomal disorder affecting females, while Duchenne muscular dystrophy is a severe X-linked recessive disorder affecting males. Although theoretically possible, very few cases of DMD associated with Turner syndrome have been reported. We report an 8 year old girl who presented with a rare association of Turner syndrome mosaicism (45X/46XringX) with Duchenne muscular dystrophy.

An ultra-rare case of 47,XXY/48,XXXY/49,XXXXY mosaic Klinefelter syndrome associated with diabetic ketosis and foot ulcer

Klinefelter syndrome (KS) is the most common chromosome aneuploidy and a common cause of infertility in males. KS patients have at least one extra X chromosome, and about 80% of patients have the karyotype 47,XXY. Twenty percent of KS patients have higher-grade aneuploidies (48,XXXY, 48,XXYY, 49,XXXXY) and exert some clinical manifestation different from those with 47,XXY. Here we report the case of a young man who initially presented with diabetic ketosis and foot ulcer and was later diagnosed as having an extremely rare mosaic variant of KS (47,XXY/48,XXXY/49,XXXXY). Clinical and laboratory features are summarized. The patient developed a severe foot ulcer with an 18-month history of diabetes. Learning disability was noted since early childhood. The patient had typical manifestations of KS, including increased height, sparse beard and body hair, and small penis. He also had some characteristic features of patients with additional sex chromosomes, including epicanthal folds, narrow palpebral fissures, prominent elbows, and undescended testicles. Severe myopia and myopic macular degeneration was also found. Lab tests revealed low testosterone and elevated FSH but normal LH levels. Chromosome analysis on lymphocytes revealed an aberration of 47,XXY/48,XXXY/49,XXXXY. This case provides information on KS patients with the extremely rare karyotype 47,XXY/48,XXXY/49,XXXXY, and also emphasizes the importance of considering KS in the differential diagnosis of a sterile male with diabetes.

Turner\u2019s syndrome mosaicism in girls with neurodevelopmental disorders: a cohort study and hypothesis

BackgroundTurner’s syndrome is associated with either monosomy or a wide spectrum of structural rearrangements of chromosome X. Despite the interest in studying (somatic) chromosomal mosaicism, Turner’s syndrome mosaicism (TSM) remains to be fully described. This is especially true for the analysis of TSM in clinical cohorts (e.g. cohorts of individuals with neurodevelopmental disorders). Here, we present the results of studying TSM in a large cohort of girls with neurodevelopmental disorders and a hypothesis highlighting the diagnostic and prognostic value.ResultsTurner’s syndrome-associated karyotypes were revealed in 111 (2.8%) of 4021 girls. Regular Turner’s syndrome-associated karyotypes were detected in 35 girls (0.9%). TSM was uncovered in 76 girls (1.9%). TSM manifested as mosaic aneuploidy (45,X/46,XX; 45,X/47,XXX/46,XX; 45,X/47,XXX) affected 47 girls (1.2%). Supernumerary marker chromosomes derived from chromosome X have been identified in 11 girls with TSM (0.3%). Isochromosomes iX(q) was found in 12 cases (0.3%); one case was non-mosaic. TSM associated with ring chromosomes was revealed in 5 girls (0.1%).ConclusionThe present cohort study provides data on the involvement of TSM in neurodevelopmental disorders among females. Thus, TSM may be an element of pathogenic cascades in brain diseases (i.e. neurodegenerative and psychiatric disorders). Our data allowed us to propose a hypothesis concerning ontogenetic variability of TSM levels. Accordingly, it appears that molecular cytogenetic monitoring of TSM, which is a likely risk factor/biomarker for adult-onset multifactorial diseases, is required.

A Novel Case of Gorlin Syndrome Mosaicism Involving an SMO Gene Mutation: Clinical, Histological and Molecular Analysis of Basaloid Tumours.

A Novel Case of Gorlin Syndrome Mosaicism Involving an SMO Gene Mutation: Clinical, Histological and Molecular Analysis of Basaloid Tumours.

Ring chromosome 20: A further contribution to the delineation of epileptic phenotype

Introduction. Ring chromosome 20 [r(20)] syndrome is a rare genetic abnormality where two arms of the 20th chromosome fuse forming a ring chromosome, resulting in intractable epilepsy and wide range of behavioral problems and cognitive deficits. Case report. We presented four patients with r (20) syndrome diagnosed between the years 2000?2018. In all patients we analyzed clinical epilepsy features (seizure semiology, seizure frequency/drug response, the presence of nonconvulsive status epilepticus), cognitive status and the phenotype characteristics. The average age of epilepsy onset was 6 years. All four patients had nocturnal epileptic events and normal brain magnetic resonance (MR) imaging. Dysmorphism was present in two children, behavioral problems also in two children and intellectual disabilities were observed in three children. R(20) syndrome mosaicism ranged between 17% and 83% of blood lymphocytes. Conclusion. Despite the small size of our group, we think that our findings have clinical relevance. Refractory child-hood onset epilepsy and especially the occurrence of nocturnal epileptic events should help physicians to recognize this chromosomopathy. Routine karyotyping can be employed to identify the patients easily.

Bypassing physiological puberty, a novel procedure of oocyte cryopreservation at age 7: a case report and review of the literature

To report the first successful oocyte cryopreservation in a prepubertal girl. Case report and review of the literature. Tertiary medical center. A 7-year-old prepubertal girl with Turner syndrome mosaicism (45,X[37]/47,XXX[15]) who underwent a novel fertility preservation procedure after fertility preservation counseling and informed decision of the parents. Controlled ovarian hyperstimulation with daily administration of 100 IU recombinant human follicle-stimulating and 50 IU recombinant human luteinizing hormone per milliliter, injection of 250 μg human chorionic gonadotropin was given 36 hours before the follicular aspiration procedure, and oocytes retrieved by a transabdominal ultrasound guided approach. Mature oocyte cryopreservation. The first cryopreservation cycle with use of a gonadotropin-releasing hormone agonist trigger failed to yield oocytes. The second cycle with human chorionic gonadotropin trigger was successful. Six oocytes were retrieved, and all were mature metaphase 2. The patient was discharged in good condition with no complications. This novel procedure bypasses the timely physiologic progression of pubertal maturation of the hypothalamic-pituitary-ovarian axis to directly target the ovaries and achieve mature ovarian follicles. This innovative approach offers a new treatment modality for prepubertal girls who need fertility preservation such as in Turner syndrome or in cases that ovarian tissue cryopreservation is contraindicated.

Trisomy 9 Mosaicism Syndrome in a Female Child

Trisomy 9 Mosaic syndrome is one of many rare syndromes. Less than 100 cases is known to date. Our case is the only one we’re aware of in the Panhandle region. We present this case to bring awareness of this rare syndrome to providers in how to facilitate management.