CHD7 disorder is a multiple congenital anomaly syndrome with a highly variable phenotypic spectrum, and includes CHARGE syndrome. Internal and external genital phenotypes frequently seen in CHD7 disorder include cryptorchidism and micropenis in males, and vaginal hypoplasia in females, both thought to be secondary to hypogonadotropic hypogonadism. Here, we report 14 deeply phenotyped individuals with known CHD7 variants (9 pathogenic/likely pathogenic and 5 VOUS) and a range of reproductive and endocrine phenotypes. Reproductive organ anomalies were observed in 8 of 14 individuals and were more commonly noted in males (7/7), most of whom presented with micropenis and/or cryptorchidism. Kallmann syndrome was commonly observed among adolescents and adults with CHD7 variants. Remarkably, one 46,XY individual presented with ambiguous genitalia, cryptorchidism with Müllerian structures including uterus, vagina and fallopian tubes, and one 46,XX female patient presented with absent vagina, uterus and ovaries. These cases expand the genital and reproductive phenotype of CHD7 disorder to include two individuals with genital/gonadal atypia (ambiguous genitalia), and one with Müllerian aplasia.
Background: Intracerebral schwannomas are rare tumors resembling their peripheral nerve sheath counterparts but localized in the CNS. They are not classified as a separate tumor type in the 2021 WHO classification. This study aimed to compile and characterize these rare neoplasms morphologically and molecularly.
Background: Kallmann syndrome (KS) is a rare genetic disorder marked by hypogonadotropic hypogonadism and either anosmia or hyposmia. It exhibits genetic heterogeneity, with mutations identified in only 30 % of cases, involving various genes such as KAL1, FGFR1, FGF8, CHD7, and SOX10. Here, we present a case of gonadotropin deficiency associated with KS, observed in both a mother and her daughter, the latter conceived through assisted reproductive technology using the mother's ovum.
The study aimed to explore the genetic basis and pathogenic variants associated with autism spectrum disorder (ASD) by performing whole-genome sequencing on 57 Japanese ASD patients and their parents.
Researchers identified potentially pathogenic variants in about 31.6% of the patients, with a higher rate (43.5%) among those with comorbid intellectual developmental disorder (IDD), highlighting specific genes like PTEN and CHD7 linked to recognized ASD phenotypes.
The findings emphasize the importance of understanding the genetic underpinnings of ASD to aid in clinical diagnosis and treatment, though no significant results were found regarding short tandem repeats or polygenic risk scores.
Kallmann syndrome is a rare disorder characterized by hypogonadotropic hypogonadism and an impaired sense of smell (anosmia or hyposmia) caused by congenital defects in the development of the gonadotropin-releasing hormone (GnRH) and olfactory neurons. Mutations in several genes have been associated with Kallmann syndrome. However, genetic testing of this disorder often reveals variants of uncertain significance (VUS) that remain uninterpreted without experimental validation.
* Despite treatment efforts including ventilator support and surgery, her condition did not improve, leading to genetic testing which revealed a mutation linked to CHARGE syndrome.
* Ultimately, the family chose to stop treatment due to the infant's poor prognosis, highlighting the importance of early diagnosis and informed decision-making in complex genetic disorders.
