What is the management approach for prenatal monosomy X (Turner syndrome)?

Management of Prenatal Monosomy X (Turner Syndrome)

Immediate Diagnostic Confirmation

When monosomy X is detected prenatally via noninvasive prenatal screening (NIPS), diagnostic testing with chorionic villus sampling (10-12 weeks) or amniocentesis (15-18 weeks) using chromosomal microarray, FISH, or MLPA is mandatory to confirm the diagnosis, as NIPS has high false-positive rates and low positive predictive value for sex chromosome anomalies. 1, 2

• A positive NIPS for monosomy X may represent fetal Turner syndrome, maternal Turner syndrome, or confined placental mosaicism—diagnostic testing distinguishes these possibilities 2
• Sophisticated genetic techniques can detect mosaicism in one-third of individuals previously thought to have monosomy X, making comprehensive chromosomal analysis essential 3, 4

Comprehensive Fetal Anatomic Evaluation

High-resolution ultrasound examination beginning at 18-22 weeks must evaluate for cardiac anomalies, polyhydramnios, intrauterine growth restriction, renal anomalies, and other structural defects, as congenital cardiovascular disease affects approximately 50% of individuals with Turner syndrome. 1, 5

• Fetal echocardiography at 18-22 weeks is mandatory to screen for bicuspid aortic valve (15-30% prevalence), aortic coarctation (7-18%), and other conotruncal defects 6, 5
• Cardiac magnetic resonance imaging provides precise measurement of aortic diameters and identifies congenital cardiovascular abnormalities that may be missed on echocardiography 6
• Fetuses with abnormal ultrasound findings have poor prognoses for survival, while those with normal ultrasounds and mosaic karyotypes have high survival rates and may have mild or no features of Turner syndrome 7

Maternal Evaluation When Fetal Karyotype is Discordant

If diagnostic fetal testing is negative for monosomy X but NIPS was positive, maternal karyotyping is required to evaluate for previously undiagnosed maternal mosaic Turner syndrome. 1, 2

• Maternal mosaic Turner syndrome carries increased risks for perinatal morbidities including cardiovascular complications 1
• Referral to maternal-fetal medicine specialist and cardiologist is mandatory if maternal mosaic Turner syndrome is confirmed 1

Genetic Counseling

Comprehensive genetic counseling must address the 50% recurrence risk if the mother has Turner syndrome, unpredictable phenotypic variability, implications for maternal-fetal health, and reproductive options including preimplantation genetic diagnosis. 1

• Discuss that intelligence is typically normal but neurodevelopmental differences may occur 3, 5
• Address that short stature is the most consistent feature and growth hormone therapy may optimize adult height 7, 3
• Explain that most affected individuals have gonadal failure requiring hormone replacement therapy, though spontaneous puberty occurs more commonly with XX mosaicism 3

Delivery Planning

Delivery at a tertiary care center experienced in neonatal Turner syndrome management is recommended, particularly when structural anomalies are identified, given the elevated prevalence of late preterm births and intrauterine growth restriction. 1

• Location and mode of delivery should be influenced by the diagnosis and presence of structural anomalies 1
• Close monitoring throughout pregnancy for cardiac function and polyhydramnios is essential 1

Cardiovascular Risk Stratification for Confirmed Cases

Baseline cardiovascular evaluation with cardiac MRI and transthoracic echocardiography is required at diagnosis due to Turner syndrome-related cardiovascular risks including aortic dissection, which is the major cause of premature mortality in adults. 6, 8, 5

• Calculate aortic size index (ASI = aortic diameter in mm / body surface area in m²) to account for typically smaller body size 6
• High-risk threshold is ASI >2.3 cm/m², requiring at least annual surveillance imaging 6
• Prophylactic aortic replacement is reasonable when ASI ≥2.5 cm/m² plus additional risk factors (bicuspid aortic valve, coarctation, uncontrolled hypertension, rapid growth >3mm/year) 6

Screening for Y Chromosome Material

Karyotype analysis must specifically evaluate for Y chromosome material, present in approximately 10% of Turner syndrome cases, as this increases gonadoblastoma risk and requires bilateral prophylactic gonadectomy. 8

Critical Counseling About Prognosis

Counsel that with modern medical management, survival to birth with normal ultrasound findings predicts good clinical outcomes, though lifetime cardiovascular surveillance and hormone replacement therapy will be necessary. 7, 3

• Emphasize that premature mortality in adults with Turner syndrome is unacceptably high, mainly from congenital heart disease complications, making lifelong cardiac surveillance non-negotiable 7, 5
• Low-dose estrogen replacement therapy initiated early can induce more physiological puberty onset and tempo, optimizing psychosocial adjustment 7, 3