Clinical and Genetic Aspects in Fetuses and Children With Sex Chromosome Disorders

N/AEnrolling By InvitationNCT07341412

University of Aarhus300 enrolled

Overview

The aim of the project is to: 1. Investigate organ development and growth in fetuses with sex chromosome disorders; 2. Investigate growth, development, and morbidity in children with sex chromosome disorders during the first years of life; 3. Delineate how variations in sex chromosome number affect the epigenetic and genetic mechanisms regulating gene expression in the placenta and in multiple tissues of the child after birth over time during early childhood; 4. Investigate the gut microbiome in children with sex chromosome disorders during the first years of life; 5. Identify the epigenetic and genetic mechanisms and placental and child-specific alterations underlying the phenotype observed in fetuses, children, and adults with sex chromosome disorders, using a deep phenotyping approach.

Study Type

OBSERVATIONAL

Enrollment

300

Conditions

Sex Chromosome Disorders

Eligibility

Sex: ALLMin age: 0 YearsMax age: 50 Years

Medical Language ↔ Plain English

Inclusion Criteria for pregnant participants in case group: Age ≥18 years Fetus with a genetically verified sex chromosome disorder Written informed consent Inclusion Criteria for pregnant participants in control group: Age ≥18 years Normal first- and second-trimester ultrasound examinations Fetal growth within the normal range Written informed consent Inclusion Criteria for mothers in the case group: Age ≥18 years at the time of pregnancy with the child Child with a genetically verified sex chromosome disorder Written informed consent Inclusion Criteria for mothers in the control group: Age ≥18 years at the time of pregnancy with the child Normal first- and second-trimester ultrasound examinations during the pregnancy Normal fetal growth during the pregnancy Written informed consent Inclusion Criteria for children in the case group: If parents share joint custody, written informed consent must be obtained from both parents Ability to undergo a physical examination Child with a genetically verified sex chromosome disorder (prenatally or postnatally diagnosed) Inclusion Criteria for children in the control group: If parents share joint custody, written informed consent must be obtained from both parents Ability to undergo a physical examination Exclusion Criteria for all groups: Severe claustrophobia Implanted magnetic material contraindicating MRI

Outcomes

Primary Outcomes

Level of DNA methylation

Levels of DNA methylation in placenta, blood, saliva, and urothelial cells

Time frame: 5 years

Level of RNA ekspression

Level of RNA ekspression in placenta, blood, saliva, and urothelial cells

Time frame: 5 years

Height

Height in centimeter (cm)

Time frame: 5 years

Weight

Weight in kilogram (kg) or gram (g)

Time frame: 5 years

Body mass index

Body mass index (BMI) in kg/m²

Time frame: 5 years

Head circumference

head circumference in centimeter (cm)

Time frame: 5 years

Fat mass and fat-free mass

Measure of fat mass and fat-free mass by PEA POD (kg)

Time frame: 5 years

Development

Bayley-4 will be used to measure development. Ages \& Stages Questionnaires will be used to measure development including social-emotional development drawing on the parents knowledge.

Time frame: 5 years

Fecal microbial diversity

Measure of fecal microbial diversity

Time frame: 5 years

Fecal microbial composition

Measurement of fecal microbial composition

Time frame: 5 year

Left ventricular ejection fraction

Left ventricular ejection fraction measured by echocardiography (%)

Time frame: 5 years

Left ventricular diameters

Left ventricular end-diastolic and end-systolic diameters measured by echocardiography (mm)

Time frame: 5 years

Interventricular septal wall thickness

Interventricular septal wall thickness measured by echocardiography (mm)

Time frame: 5 years

Heart rate

Heart rate (beats per minute) measured by electrocardiogram

Time frame: 5 years

PR interval

PR interval (ms) measured by electrocardiogram

Time frame: 5 years

QRS duration

QRS duration (ms) measured by electrocardiogram

Time frame: 5 years

Corrected QT interval

Corrected QT interval (ms) measured by electrocardiogram

Time frame: 5 years

Blood pressure

Systolic and diastolic blood pressure (mmHg)

Time frame: 5 years

Congenital heart malformation

Congenital heart malformation assessed by echocardiography

Time frame: 5 years

Aorta diameter

Aorta diameter (mm) measured by echocardiography

Time frame: 5 years

Aortic valve mean gradient

Measure of aortic valve mean gradient (mmHG)

Time frame: 5 years

Mitral valve mean gradient

Measure of mitral valve mean gradient (mmHg)

Time frame: 5 years

Transaortic doppler flow

Measure of transaortic doppler flow (m/s)

Time frame: 5 years

Fetal brain volume

Fetal brain volume measured by MRI (cm³)

Time frame: 5 years

Fetal heart volume

Fetal heart volume measured by MRI (cm³)

Time frame: 5 years

Fetal kidney volume

Fetal kidney volume measured by MRI (cm³)

Time frame: 5 years

Fetal lever volume

Fetal lever volume measured by MRI (cm³)

Time frame: 5 years

Fetal spleen volume

Fetal spleen volume measured by MRI (cm³)

Time frame: 5 years

Fetal gonadal volume

Fetal gonadal volume measured by MRI (cm³)

Time frame: 5 years

Secondary Outcomes

Left ventricular mass

Calculation of left ventricular mass (g)

Time frame: 5 years

Clinical and Genetic Aspects in Fetuses and Children With Sex Chromosome Disorders

Overview

Conditions

Eligibility

Locations (1)

Outcomes

Primary Outcomes

Secondary Outcomes