ABSTRACT
Pentasomy X is a sex chromosome anomaly caused by the presence of three extra X chromosomes in females (49,XXXXX instead of 46,XX) and is probably due to a nondisjunction during the meiosis. So far, only five cases prenatally diagnosed were described. The main features in 49,XXXXX karyotype include severe intellectual disability with delayed speech development, short stature, facial dysmorphisms, osseous and articular abnormalities, congenital heart malformations, and skeletal and limb abnormalities. Prenatal diagnosis is often difficult due to the lack of a clear echographic sign like nuchal translucency (NT), and mostly cases were postnatally described. We report the first case of a 49,XXXXX female that was detected by non-invasive prenatal screening (NIPS), quantitative fluorescence polymerase chain reaction (QF-PCR) and a fetal karyotype.
ABSTRACT
Mutations in the HSD17B3 gene cause HSD17B3 deficiency and result in 46, XY Disorders of Sex Development (46, XY DSD). The diagnosis of 46, XY DSD is very challenging and not rarely is confirmed only at older ages, when an affected XY female presents with primary amenorrhea or develops progressive virilization. The patient described in this paper represents a case of discrepancies between non-invasive prenatal testing (NIPT) and ultrasound based fetal sex determination detected during prenatal screening. Exome sequencing was performed on the cell free fetal DNA (cffDNA), amniotic fluid, and the parents. Libraries were generated according to the manufacturer's protocols using TruSight One Kits (Illumina Inc., San Diego, CA, USA). Sequencing was carried out on NEXT Seq 500 (Illumina) to mean sequencing depth of at least 100×. A panel of sexual disease genes was used in order to search for a causative variant. The finding of a mutation (c.645 A>T, p.Glu215Asp) in HSD17B3 gene in amniotic fluid as well as in cffDNA and both parents supported the hypothesis of the HSD17B3 deficiency. In conclusion, we used clinical exome sequencing and non-invasive prenatal detection, providing a solution for NIPT of a single-gene disorder. Early genetic diagnoses are useful for patients and clinicians, contribute to clinical knowledge of DSD, and are invaluable for genetic counseling of couples contemplating future pregnancies.
Subject(s)
Cell-Free Nucleic Acids/genetics , Disorder of Sex Development, 46,XY/genetics , Gonadal Dysgenesis, 46,XY/genetics , Sexual Development/genetics , 17-Hydroxysteroid Dehydrogenases/genetics , Adult , Female , Genetic Testing/methods , High-Throughput Nucleotide Sequencing/methods , Homozygote , Humans , Mutation/genetics , Phenotype , Pregnancy , Prenatal Diagnosis/methods , Virilism/genetics , Exome Sequencing/methods , Young AdultABSTRACT
BACKGROUND: Identifying the cause of intracerebral hemorrhage (ICH) is relevant to optimize its management. We aimed to assess the applicability and utility of the Edinburgh CT criteria for cerebral amyloid angiopathy (CAA) in an unselected cohort of hospitalized patients. PATIENTS AND METHODS: We retrospectively applied the Edinburgh criteria to the first available brain CTs of patients hospitalized for a first-ever lobar ICH in the district of L'Aquila from 2011 to 2017. ICH characteristics and outcomes were compared according to the presence of the Edinburgh CT criteria, including associated subarachnoid hemorrhage (aSAH) and finger-like projections (FLPs). The outcome of ICH in-hospital mortality was assessed with multivariate logistic regression analysis. We adopted the Edinburgh criteria, age, NIHSS and Glasgow Coma Scale scores, systolic blood pressure, antiplatelet treatment, ICH volume, and intraventricular extension on admission as covariates. RESULTS: Of 178 patients with lobar ICH, 52 (29.2%) had aSAH+FLPs, 60 (33.7%) aSAH only, 1 (0.6%) FLPs, and 65 (36.5%) none. Patients with aSAH+FLPs were older (79.0 ± 9.2 years) than those with only one criterion or none (74.0 ± 15.3 and 72.2 ± 13.8 years, respectively; P = 0.020). Patients with aSAH+FLPs also had more severe ICH at onset, higher in-hospital case-fatality (log rank test P = 0.003) and higher mRS scores at discharge (P < 0.001) as compared to those fulfilling one or none of the Edinburgh criteria. Low Glasgow Coma Scale score was the only factor independently associated to in-hospital case-fatality (odds ratio per point increase 0.51; 95% confidence interval, 0.32-0.91; P = 0.021). DISCUSSION: Our data suggest the applicability of the Edinburgh CT criteria in a hospital setting. The presence of those criteria reflects ICH clinical severity. CONCLUSIONS: Applying the Edinburgh CT criteria might help refining the diagnosis and improving the management of patients with lobar ICH.
