Turner syndrome diagnostic study of choice
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Akash Daswaney, M.B.B.S[2]
Overview
The diagnostic study of choice for the diagnosis of Turner syndrome is karyotype analysis of 30 blood lymphocytes. Examination of additional cells , polymerase chain reaction, fluorescent in situ hybridization, Southern blotting, restricted fragment length polymorphisms and new generation gene sequencing techniques may be employed following the interpretation of the initial karyotype.
Diagnostic Study of Choice
- The diagnostic study of choice for the diagnosis of Turner syndrome is karyotype analysis of 30 blood lymphocytes.
- Examination of additional cells , polymerase chain reaction, fluorescent in situ hybridization, Southern blotting, restricted fragment length polymorphisms and new generation gene sequencing techniques may be employed following the interpretation of the initial karyotype.
Prenatal Visit – Ultrasound + Karyotype analysis
- Turner syndrome may be diagnosed or suspected prenatally because of an ultrasonography showing a left-sided cardiac defect, renal anomalies, growth retardation, relatively short limbs, fetal edema , cystic hygroma, polyhydramnios, brachycephaly. [1]
- A Turner syndrome karyotype may be discovered fortuitously when fetal chromosome analysis is performed for reasons not associated with an increased incidence of Turner syndrome, such as advanced maternal age.
- Noninvasive cell free fetal DNA has a low positive predictive value and is not recommended during a prenatal visit.
- A maternal serum screening with multiple markers (decreased maternal serum alpha fetoprotein, decreased unconjugated estriol , increased human chorionic gonadotropin, increased inhibin B) may suggest Turner syndrome.
- If an abnormality associated with Turner syndrome is diagnosed by ultrasonography or if multiple marker screening is positive, the recommended follow-up is fetal karyotyping using amniotic fluid cells obtained by amniocentesis or fetal blood obtained by percutaneous umbilical blood sampling when the karyotype is needed more rapidly.
- The karyotype does not determine the phenotype.
- A diagnosis of Turner syndrome made solely by fetal karyotyping should be followed up with careful ultrasonography to define the phenotypic abnormalities as accurately as possible.
- When a prenatal diagnosis of Turner syndrome, counseling is ordinarily provided for the family by a medical geneticist, a pediatric endocrinologist, or another physician with special knowledge of Turner syndrome.
Birth to 1 month of age – Confirmation of prenatal diagnosis OR New Karyotype analysis + Additional cytogenic studies
- If the diagnosis has not been made? [1]
- The standard 30 cell karyotype analysis should be performed if a single clinical feature (short stature, hydrops fetalis, cystic hygroma, characteristic facial features) or two commonly associated conditions (Madelung deformity, cardiac or renal anomalies, multiple nevi) are seen.
- In patients with virilization but absent Y chromosomal abnormalities on initial analysis, fluorescent in situ hybridization (FISH) or PCR techniques specific for cryptic Y material may e performed.
- Polymerase chain reaction can also be used to detect methylation sites indicative of inactivateded X chromosomes.
- Females with short stature and deletion of the distal region of the paternal X chromosome including the SHOX gene are generally not diagnosed with Turner syndrome.
- Similarly, individuals with deletions of Xq24, with primary or secondary amenorrhea and without short stature are diagnosed as premature ovarian failure.
- Small deletions of the long arm of the X-chromosome distal to Xq24 are not included in the diagnosis of Turner syndrome.
- Next generation sequencing technologies such as whole genomes, exomes and gene panel sequencing may be used in newborn screening.
- Does the diagnosis need to be confirmed?
- Perform a cytogenic study of a peripheral blood smear (blood mononuclear cells) or other tissue (e.g. skin biopsy for cell culture or buccal mucosa/ bladder epithelial cell smear for FISH) after consulting with the physician.
- In the presence of mosaicism, look for the presence of Y chromosome which may infer that there is an increase for gonadoblastoma.
- Ortolani and Barlow maneuvers for congenital hip dysplasia. [1]
- Hearing tests performed and compared with newborn hearing screening results.
- Consult with a pediatric cardiologist. Studies have shown that echocardiographs or ultrasonographies should be performed by pediatric cardiologists as their interpretation skills are better. Also discuss the need for antibiotic prophylaxis for bacterial endocarditis.
- Check for brachiofemoral delay and an auscultatory gap.
- Consult with an endocrinologist to discuss about estrogen replacement therapy, growth hormone therapy and the future need for hormone replacement therapy and assisted reproductive techniques.
- Renal Ultrasound for structural abnormalities such as horse-shoe shaped kidney, duplicate ureter.
- Inform that lymphedema may persist.
- Counsel regarding the cosmetic and functional effect of abnormalities and treatment for same.
- Feeding difficulties may be present due to inadequate sucking and swallowing reflexes.
- Patient education regarding Turner syndrome and how to approach society regarding this.
- Height weight and a complete physical examination.
- Complete blood count, fasting blood glucose, lipid profile, bone mineral density, and renal, liver and thyroid function tests.
1 month to 5 years of age
- Comparison of present weight with previous weights is important as lymphedema dissipates due to diuresis in the first month of the child’s life.
- Remember that Turner syndrome is the most common cause of short stature in an otherwise healthy girl. [2]
- Assess for indications for of growth hormone therapy. Discuss risks and benefits.
- Check for hypertension, brachiofemoral delay and auscultatory gap. If hypertension persists, treat aggressively. Consult with a pediatric cardiologist.
- If a cardiac anomaly is present, refer to a pediatric cardiologist and suggest antibiotic prophylaxis for infective endocarditis.
- If urinary tract abnormalities are present, perform a urinalysis and culture.
- Perform regular hearing screens. Discuss risk factors (bottle feeding, passive smoking, group child care) for otitis media and perform an evaluation for same. If present, refer to an otolaryngologist to discuss the placement of tympanostomy tubes and advise avoidance of loud noises.
- Evaluate for speech delays (which may be secondary to hearing loss).
- Refer to pediatric specialist and development intervention programs if indicated.
- Check for developmental delays and learning difficulties, especially visual spatial deficits. A thorough evaluation prior to entry into (and according to) preschool guidelines is warranted.
5 to 13 years of age
- As soon as the child is capable of understanding, Turner syndrome should be discussed with her. [3]
- Counselling regarding short stature and difficulties in school such as learning disabilities, attention deficits, hyperactivity and lack of social skills.
- Optimize bone mineral density and advise Vitamin D supplementation.
- Monitor growth and assess the need for adding oxandrolone to growth hormone therapy.
- Check for hypertension, brachiofemoral delay and an auscultatory gap. Treat accordingly and aggressively.
- Perform regular hearing screens. Discuss risk factors for otitis media and perform an evaluation for same. If present, refer to an otolaryngologist, discuss the placement of tympanostomy tubes and advise avoidance of loud noises.
- Screen thyroid function test at 1-2 year intervals.
- Screen for urinary tract abnormalities.
- Screen child’s dentition for malocclusion.
- Screen for kyphosis/scoliosis.
- Screen for type 2 diabetes mellitus – glycosylated hemoglobin and oral glucose tolerance test.
- Check ovarian reserve using serum lutenizing hormone, serum follicle stimulating hormone, serum gonadotrophin releasing hormone and anti Mullerian hormone levels.
13-21 years of age
- Monitor for increased incidence of pigmented nevi during adolescence and remove if they rub against clothing.[1]
- Check for hypertension, brachiofemoral delay and an auscultatory gap. Treat accordingly and aggressively.
- Screen for hyperlipidemia once during adolescence, with a fasting lipid profile.
- Screen for kyphosis/scoliosis annually.
- Perform regular hearing screens. Discuss risk factors for otitis media and perform an evaluation for same. If present, refer to an otolaryngologist, discuss the placement of tympanostomy tubes and advise avoidance of loud noises.
- Check ovarian reserve using serum lutenizing hormone, serum follicle stimulating hormone, serum gonadotrophin releasing hormone and anti Mullerian hormone levels.
- Refer to a pediatric endocrinologist to discuss sex hormone replacement therapy.[3]
- Refer to a cardiologist regardless of whether previous investigations suggested cardiac abnormalities or not.
- Screen thyroid function test at 1-2 year intervals.
- Performance in school, social adaptation, immaturity for their age , assisted reproductive techniques, sexual activity, sexually transmitted diseases and spontaneous pregnancies are issues that need to be discussed with the patient.
References
- ↑ 1.0 1.1 1.2 1.3 Shankar RK, Backeljauw PF (2018). "Current best practice in the management of Turner syndrome". Ther Adv Endocrinol Metab. 9 (1): 33–40. doi:10.1177/2042018817746291. PMC 5761955. PMID 29344338.
- ↑ Cui X, Cui Y, Shi L, Luan J, Zhou X, Han J (2018). "A basic understanding of Turner syndrome: Incidence, complications, diagnosis, and treatment". Intractable Rare Dis Res. 7 (4): 223–228. doi:10.5582/irdr.2017.01056. PMC 6290843. PMID 30560013.
- ↑ 3.0 3.1 Frías JL, Davenport ML, Committee on Genetics and Section on Endocrinology (2003). "Health supervision for children with Turner syndrome". Pediatrics. 111 (3): 692–702. doi:10.1542/peds.111.3.692. PMID 12612263.