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

NCT07341412 | Enrolling By Invitation

• 1 other identifier: 1-10-72-65-24
• Study Type: observational
• Target: 300
• Locations: 1 country
• Sites: 1

Brief Summary

The aim of the project is to:

1. 1.Investigate organ development and growth in fetuses with sex chromosome disorders;
2. 2.Investigate growth, development, and morbidity in children with sex chromosome disorders during the first years of life;
3. 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. 4.Investigate the gut microbiome in children with sex chromosome disorders during the first years of life;
5. 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.

Conditions

Sex Chromosome Disorders

Keywords

Turner syndrome; Klinefelter syndrome; Triple X syndrome; Double Y syndrome; 45,X/46,XY syndrome

Outcome Measures

Primary Outcomes (29)

• Level of DNA methylation

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

  5 years

• Level of RNA ekspression

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

  5 years

• Height

  Height in centimeter (cm)

  5 years

• Weight

  Weight in kilogram (kg) or gram (g)

  5 years

• Body mass index

  Body mass index (BMI) in kg/m²

  5 years

• Head circumference

  head circumference in centimeter (cm)

  5 years

• Fat mass and fat-free mass

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

  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.

  5 years

• Fecal microbial diversity

  Measure of fecal microbial diversity

  5 years

• Fecal microbial composition

  Measurement of fecal microbial composition

  5 year

• Left ventricular ejection fraction

  Left ventricular ejection fraction measured by echocardiography (%)

  5 years

• Left ventricular diameters

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

  5 years

• Interventricular septal wall thickness

  Interventricular septal wall thickness measured by echocardiography (mm)

  5 years

• Heart rate

  Heart rate (beats per minute) measured by electrocardiogram

  5 years

• PR interval

  PR interval (ms) measured by electrocardiogram

  5 years

• QRS duration

  QRS duration (ms) measured by electrocardiogram

  5 years

• Corrected QT interval

  Corrected QT interval (ms) measured by electrocardiogram

  5 years

• Blood pressure

  Systolic and diastolic blood pressure (mmHg)

  5 years

• Congenital heart malformation

  Congenital heart malformation assessed by echocardiography

  5 years

• Aorta diameter

  Aorta diameter (mm) measured by echocardiography

  5 years

• Aortic valve mean gradient

  Measure of aortic valve mean gradient (mmHG)

  5 years

• Mitral valve mean gradient

  Measure of mitral valve mean gradient (mmHg)

  5 years

• Transaortic doppler flow

  Measure of transaortic doppler flow (m/s)

  5 years

• Fetal brain volume

  Fetal brain volume measured by MRI (cm³)

  5 years

• Fetal heart volume

  Fetal heart volume measured by MRI (cm³)

  5 years

• Fetal kidney volume

  Fetal kidney volume measured by MRI (cm³)

  5 years

• Fetal lever volume

  Fetal lever volume measured by MRI (cm³)

  5 years

• Fetal spleen volume

  Fetal spleen volume measured by MRI (cm³)

  5 years

• Fetal gonadal volume

  Fetal gonadal volume measured by MRI (cm³)

  5 years

Secondary Outcomes (1)

• Left ventricular mass

  5 years

Study Arms (6)

Pregnant women carrying a fetus with a sex chromosome disorder

Pregnant women carrying a fetus without a sex chromosome disorder (Controls)

Mothers of a child with a sex chromosome disorder

MOthers of a child without a sex chromosome disorder (Controls)

Children with a sex chromosome disorder

Children without a sex chromosome disorder (Controls)

Eligibility Criteria

• Age: 0 Years - 50 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)
• Sampling Method: Non-Probability Sample

Study Population

Recruitment of cases will take place at obstetric departments, departments of clinical genetics, and pediatric departments throughout Denmark. Recruitment of controls will take place at the Department of Gynecology and Obstetrics and Department of Pediatrics, Aarhus University Hospital as well as via Facebook groups.

You may qualify if:

• Age ≥18 years Fetus with a genetically verified sex chromosome disorder Written informed consent
• Age ≥18 years Normal first- and second-trimester ultrasound examinations Fetal growth within the normal range Written informed consent
• Age ≥18 years at the time of pregnancy with the child Child with a genetically verified sex chromosome disorder Written informed consent
• 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
• 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)
• If parents share joint custody, written informed consent must be obtained from both parents Ability to undergo a physical examination

You may not qualify if:

• Severe claustrophobia Implanted magnetic material contraindicating MRI

Sponsors & Collaborators

• University of Aarhus: lead
• Aarhus University Hospital: collaborator

Study Sites (1)

Aarhus University Hospital

Aarhus, 8200, Denmark

Location

Biospecimen

Retention: SAMPLES WITH DNA

blood, saliva, urine, feces, placenta

MeSH Terms

Conditions

Sex Chromosome Disorders; Turner Syndrome; Klinefelter Syndrome; Triple X syndrome; XYY Karyotype

Condition Hierarchy (Ancestors)

Chromosome Disorders; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Genetic Diseases, Inborn; Gonadal Dysgenesis; Disorders of Sex Development; Urogenital Abnormalities; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Sex Chromosome Disorders of Sex Development; Male Urogenital Diseases; Heart Defects, Congenital; Cardiovascular Abnormalities; Cardiovascular Diseases; Heart Diseases; Gonadal Disorders; Endocrine System Diseases; Hypogonadism; Abnormal Karyotype; Chromosome Aberrations; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Sex Chromosome Aberrations

Study Officials

• Anne Skakkebæk, MD, PHD

  Aarhus University Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 12, 2025
• First Posted: January 14, 2026
• Study Start: September 1, 2024
• Primary Completion (Estimated): January 1, 2034
• Study Completion (Estimated): January 1, 2034
• Last Updated: January 14, 2026

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

DK (1)