The prevalence, incidence, and associated factors of liver disease (LD) in Turner syndrome (TS) remain uncertain. A meta-analysis was performed to quantify LD burden in TS. Four electronic databases were searched through June 2025 for observational studies involving karyotype-confirmed individuals with TS. LD was defined by raised serum liver enzymes (RLE), International Classification of Diseases codes, imaging, or histology. Pooled prevalence, incidence, and odds ratios (OR) with 95% confidence intervals (CI) were calculated. Forty studies from 19 countries with aggregate data on 9728 young TS individuals (median age 25.5 years, IQR 16.8-30.7) were included. Prevalences of RLE, steatotic LD (SLD), and significant/advanced liver fibrosis were 26.9% (95% CI 19.7-35.6), 22.3% (9.9-42.9), and 12.2% (2.6-41.7), respectively. Incidence of RLE was 16.7 per 1000 person-years (7.6-36.8). Compared to age-matched healthy controls, TS individuals had higher odds of RLE (OR 3.96 [95% CI 1.45-10.84]), SLD (OR 4.03 [1.86-8.70]), and significant/advanced fibrosis (OR 5.74 [2.99-11.01]). Compared to X monosomy, isochromosome Xq conferred a higher risk of RLE (OR 1.55 [1.15-2.10]), while mosaicism without structural abnormalities was protective (OR 0.54 [0.32-0.89]). Ring X or Y chromosome material carried risks like X monosomy. Hormone replacement therapy was not associated with an increased risk of RLE (OR 1.10 [0.79-1.53]). Liver disease is common in individuals with TS, with a 4-6 times higher risk than age-matched healthy females. X chromosome abnormalities are more strongly associated with an increased liver disease risk than hypogonadism.

Mixed gonadal dysgenesis is characterized by abnormal genital appearance and chromosomal mosaicism. A wide spectrum of clinical manifestations can occur, ranging from females (with or without Turner syndrome) to phenotypically normal males with some degree of genital ambiguity. In this context, uncommon mosaic karyotypes are associated with distinctive phenotypic characteristics. Here, we present the case of an 18-year-old girl with primary amenorrhea, delayed puberty, and a rare mosaic karyotype pattern. Clinical data were collected, and karyotyping was performed on peripheral blood samples. Polymerase chain reaction amplification for the sex-determining region Y protein (SRY) gene was also conducted. The patient presented with delayed puberty and primary amenorrhea. Her hormonal profile was consistent with hypergonadotropic hypogonadism. Pelvic magnetic resonance imaging revealed a small uterus. Echocardiography identified the presence of a bicuspid aortic valve. Karyotyping demonstrated a 46,XY/45,X/46,X,r(Y) pattern, indicating mosaicism for monosomy X and two cell lines: 45,X and 46,X,r(Y). The SRY gene was detected. Gonadal pathological investigation confirmed streak gonads consistent with gonadal dysgenesis and evidence of gonadoblastoma. Complicated cases with mosaic chromosomal patterns can exhibit a wide range of phenotypic features, from apparently normal males with variable external genitalia to females with or without characteristics of Turner syndrome. These phenotypic discrepancies are not directly related to the number of mosaic cells or the specific location of Y chromosome breakage. Therefore, in cases of primary amenorrhea with genotype-phenotype discrepancies, a multidisciplinary approach is essential to guide appropriate sex determination and management.

We report a 27-year-old male with a rare chromosomal anomaly involving a ring Y chromosome (RCY). Our patient presented with severe oligozoospermia in the absence of other overt phenotypic abnormalities and was ultimately found to have mosaicism involving a ring Y chromosome. This case highlights the importance of considering structural Y chromosome abnormalities in the evaluation of male infertility, even in individuals with otherwise normal pubertal development and secondary sexual characteristics. RCY is a rare but important genetic cause of male infertility and should be considered in the evaluation of severe oligozoospermia or azoospermia. The clinical phenotype of RCY ranges from a normal male phenotype with infertility to phenotypic females with features of Turner syndrome. This is influenced by the presence or absence of Y-linked genes and the degree of 45,X mosaicism. The presence of a 45,X cell line in individuals with RCY mosaicism has been associated with gonadal anomalies, particularly dysgenesis and cryptorchidism.

Turner syndrome (TS) is a sex chromosome disorder affecting phenotypic females who have one intact X chromosome and a completely or partially missing second sex chromosome. It was first described approximately a century ago by Seresevskij, Ullrich and Turner. However, the cytogenetic basis of TS was only reported by Ford in 1959 following Tjio and Levan's optimisation of chromosome visualisation. TS karyotypes include classic monosomy X (40%-50%); monosomy X mosaicism (3%-25%); isochromosome X (10%-18%); ring X (10%-16%); mosaicism for monosomy X and a normal or structurally abnormal Y chromosome (6%-12%); deletion Xp (< 5%) and unbalanced X-autosome translocation (< 2%). While parental age does not affect the complete loss of one X chromosome, the paternal X chromosome is absent in three-quarters of patients with TS. Clinically, detecting the parental origin of the remaining X chromosome is not currently useful in routine TS care. Recurrence risk is low for phenotypically normal parents with a child diagnosed with TS. Pregnancy loss is the outcome for the majority (~99%) of TS cases; however, prenatal ultrasound findings for foetuses with TS may include abnormalities like cystic hygroma and hydrops. Postnatal phenotype for patients with TS includes short stature, delayed puberty, ovarian dysgenesis, hypergonadotropic hypogonadism, infertility, cardiac defects, endocrine, metabolic and autoimmune disorders. This review aims to outline clinical indications for testing, describe test methodologies, provide genetic test result examples that highlight complex TS karyotype diagnoses, summarise clinical management options and discuss the phenomenon of 'normal' sex chromosome loss with advancing age.

When a chromosome undergoes 2 distal breaks and the broken ends join together, they form a ring chromosome. Ring 21 syndrome is described with a phenotype with minor dysmorphisms, thrombocytopenia, psychomotor and language delay. The objective of this work is to display 2 cases of male patients with ring chromosome 21. The first case was a 5-year-old male patient, with psychomotor and language delay. Broad forehead with prominent metopic suture, bilateral epicanthic fold, hypotelorism, left esotropia, low-set asymmetrical pinnae, micrognathia, lower extremities with deep plantar folds. Karyotype 46,XY,r(21)(p11.2q21)[25]. The second case was an 8-year-old male patient with psychomotor and language delay. Skull with flattened occiput, triangular facies, midfacial flattening, palpebral fissures directed downwards, bilateral epicanthic fold, low-set and asymmetrical pinnae, micrognathia, prominent asymmetrical thorax on the right side, hands with irregular palmar folds. Karyotype: 46,XY,r(21)(p11q22)[25]. Craniofacial dysmorphisms with psychomotor and language delay were the most relevant clinical data in both cases. Cuando un cromosoma sufre 2 rupturas distales y los extremos rotos se unen, forman un cromosoma en anillo. El síndrome del anillo 21 se describe con un fenotipo con dismorfias menores, trombocitopenia, retraso psicomotor y del lenguaje. El objetivo de este trabajo es presentar 2 casos de pacientes del sexo masculino con cromosoma 21 en anillo. el primer caso fue un paciente de 5 años con retraso en el desarrollo psicomotor y del lenguaje, frente amplia con sutura metópica prominente, pliegue epicántico bilateral, hipotelorismo, endotropia izquierda, pabellones auriculares asimétricos de baja implantación, micrognatia, extremidades inferiores con pliegues plantares profundos. Su cariotipo fue 46,XY,r(21)(p11.2q21)[25]. El segundo caso fue un paciente de 8 años con retraso en el desarrollo psicomotor y del lenguaje, cráneo con occipucio aplanado, facies triangular, aplanamiento mediofacial, fisuras palpebrales dirigidas hacia abajo, pliegue epicántico bilateral, pabellones auriculares de implantación baja y asimétricos, micrognatia, tórax asimétrico prominente del lado derecho y manos con líneas palmares irregulares. Su cariotipo fue 46,XY,r(21)(p11q22)[25]. las dismorfias craneofaciales con retraso psicomotor y del lenguaje fueron los datos clínicos más relevantes en ambos casos.