Late to Diagnosis: Turner Syndrome

A 9-year-old girl presents for annual well visit. Mother expresses a concern for her daughter’s short stature. By mother’s report, the girl has always been petite and is the shortest in her class. Family genetics for height indicate tall stature; she is notably small for the family.

Her past medical history is unremarkable other than an ongoing issue of reoccurring otitis media. Birth history indicates that she was born full term, SVD. Birth weight was 6 lbs., 6 ozs., and length was normal. Review of systems is unremarkable. Overall, she is described as very healthy. She denies any medical complaints. School performance is good but she requires additional support with math.

Physical examination reveals she is well appearing though short for age. Height is 2.5th percentile, and weight is 30th percentile. She is prepubertal. Her cardiac and respiratory exams are normal. Mild high arched palate is noted. Mild cubitus valgus is noted. The remainder of examination is unremarkable.

Discussion: The diagnosis is Turner syndrome (TS).

Turner syndrome is a syndromic condition resulting from complete or partial absence of the second sex chromosome. Diagnosis is made by chromosome analysis. The most common features of Turner syndrome include significant short stature, gonadal dysgenesis and ovarian failure leading to lack of or incomplete puberty, cardiac anomalies, and renal anomalies. Since short stature is the most common presenting sign of Turner syndrome, a chromosome analysis is indicated in all girls <5th percentile for height. Turner syndrome occurs in 1 of 2500 live female births. Other common phenotypic features include webbed neck, low hair line, low-set ears, high arched palate, pigmented nevi, dysplastic nails, ptosis, strabismus, shortened 4th and 5th metacarpals and metatarsals, and cubitus valgus (wide carrying angle). While 95% of girls with Turner syndrome have short stature, many have few or no other phenotypic features, often resulting in late or missed diagnosis.

Mosaicism can occur, leading to a milder presentation and often making recognition of the condition more difficult. Patients with mosaicism may have less significant short stature and may experience spontaneous pubertal onset but may not have enough ovarian function to complete the pubertal process. In such cases, failure to progress completely through the puberty process and achieve menarche often leads to medical attention.

Coarctation of the aorta and bicuspid aortic valves are the most common cardiac anomalies. Hypertension is also common. Renal anomalies include horseshoe kidneys or duplication of the collecting system. Urinary tract infections can be common if renal anomalies are present. Patients may also experience frequent/reoccurring otitis media. Pigmented nevi (benign) are common in girls with TS. Scoliosis is common, requiring ongoing screening. There is a higher incidence of autoimmune disorders, including acquired hypothyroidism, celiac disease, and diabetes. Screening for these conditions will be required every 1 to 2 years depending on age. Learning differences can occur at slightly higher incidence and may include visual spatial deficits, nonverbal learning disability, and attention deficit. Psychosocial issues may include difficulty with social skills and interactions with age-matched peers.

Newly diagnosed patients with TS require endocrinology, genetics, and cardiology evaluations and a baseline renal ultrasound. Patients are managed by the Division of Endocrinology for treatment of growth and pubertal issues but also for overall disease management and surveillance. Treatment of short stature includes growth hormone therapy, which can improve final height. Hormonal therapy to initiate and maintain puberty is indicated if gonadal dysgenesis results in lack of spontaneous pubertal onset or incomplete puberty. Gonadal dysgenesis puts girls with TS at significant risk for infertility. Counseling and psychosocial support may be indicated to address issues related to short stature, delayed puberty, adjustment to diagnosis, and peer relationships. Support groups are valuable for patients and parents.

Common Findings/Features of Turner Syndrome

Pertinent findings on review of systems

History of:

• Reoccurring otitis media (past the age of 6-7)
• Hearing loss
• Urinary tract infection
• Cardiac anomaly
• Learning issues: non-verbal learning disability, visual spatial deficits, attention deficit
• Social skills deficits

Phenotypic features

• Short stature
• Lack of pubertal onset
• Low hair line
• Low set ears
• High arched palate
• Dental overcrowding
• Ptosis
• Strabismus
• Webbed neck
• Broad chest
• Hypoplastic nipples
• Cubitus valgus (wide carrying angle)
• Dysplastic nails
• Shortened 4th and 5th metacarpals and metatarsals
• Pigmented nevi

Subspecialty evaluations required

• Endocrinology
• Genetics
• Cardiology
• Renal ultrasound
• Audiology
• ENT
• Ophthalmology
• Dental/Orthodontia
• Orthopedics
• Dermatology
• Learning Evaluation

Laboratory evaluation

• Thyroid function tests
• Hemoglobin A1c
• Celiac panel
• Lipid panel

Clinical Diagnosis/ Presentation of Turner Syndrome by Age

In utero

• Genetic testing:  amniocentesis, CVS
• Cardiac defect noted on fetal ultrasound

Newborn period

• Lymphedema of hands or feet
• Webbed neck
• Cardiac anomaly

School age

• Short stature
• Other phenotypic features

Adolescent

• Short stature
• Lack of pubertal onset
• Pubertal onset but lack of progression
• Primary amenorrhea

Patient-family education and support programs

• Turner Syndrome Society: turnersyndrome.org
• Patient/family Educational Day
  “Spring Fling for Turner Syndrome,” hosted by the Division of Endocrinology Turner Syndrome Program at CHOP, is scheduled for May 18, 2013.
• Learn and Connect
  Learn and Connect sessions are held twice in the fall at the Voorhees, New Jersey, Specialty Care Center, and twice in the spring at our King of Prussia, Pennsylvania, Specialty Care Center. The sessions are for parents of girls with Turner syndrome. The goal is to bring parents together to network with other parents and provide an opportunity to learn about medical issues and parenting issues common in TS.

References and Suggested Readings

Bondy CA. Care of girls and women with Turner syndrome: a Guideline of the Turner Syndrome Study Group. JCEM. 2007;92(1):10-25.

Donaldson, MDC et al. Optimising management in Turner syndrome: from infancy to adult transfer. Arch Dis Child. 2006;91:513-520.

Referral Information

To refer a patient or more information about Turner syndrome, visit the Turner Syndrome Program or contact Denise Gruccio, MSN, CRNP, at 215-590-3174.