A Chinese girl with Turner syndrome and Duchenne muscular dystrophy: diagnosis and management of this “dual diagnosis”
Imagine a 9-year-old girl who can’t jump, struggles to stand from a squat, and tires after short walks. For years, her short stature was blamed on family genetics—but when muscle weakness worsened, doctors uncovered something extraordinary: a dual diagnosis of Turner syndrome (TS) and Duchenne muscular dystrophy (DMD). This combination is so rare—only seven cases have been reported worldwide since 1965—that a team from Beijing Children’s Hospital set out to share their experience, offering hope and guidance for families facing similar rare conditions.
The case, detailed by Jia-Jia Chen, Bing-Yan Cao, and colleagues from the Department of Endocrinology, Genetics and Metabolism at Beijing Children’s Hospital (Capital Medical University), was published in the Chinese Medical Journal in 2021. The family provided written consent for the case to be shared, with steps taken to protect the patient’s identity (though full anonymity can’t be guaranteed).
The Patient’s Journey
The 9-year-old from Hebei Province was referred for three key symptoms: short stature, muscle weakness, and a waddling gait. Since age 3, she’d been smaller than peers—by 4.75, her height was 91.8 cm (-4.21 standard deviation [SD], meaning far below average). As she grew, new challenges emerged: she couldn’t jump, struggled to climb stairs, and tired easily.
A physical exam revealed classic TS features—low posterior hairline, misshapen ears, pigmented nevi (moles), a short webbed neck, shield chest, inverted nipples, lordosis (curved lower back), cubitus valgus (elbows that turn outward), and lymphedema (swelling) in hands and feet. She also had traits unusual for TS: up-slanting eyes, strabismus (crossed eyes), and a small mouth. For DMD, she showed proximal muscle weakness, a positive Gowers’ sign (using hands to push up from the floor—common in muscle disorders), and calf hypertrophy (enlarged calves from scar tissue).
Testing Confirms a Dual Diagnosis
Lab results painted a clear picture of muscle damage: serum creatine kinase (CK)—a marker for muscle injury—spiked to 6566 IU/L (normal: 25–200 IU/L). Electromyography (EMG) showed myogenic lesions (damage to muscles, not nerves). Intellectual testing (Wechsler nonverbal scale) scored 66, indicating borderline mild impairment. Imaging ruled out heart or kidney issues.
Genetic testing was the breakthrough:
- TS: Karyotype analysis showed 45,X (no second X chromosome, the hallmark of TS). A single nucleotide polymorphism (SNP) array confirmed the missing X.
- DMD: A frame-shift variant (a missing “T” in the DMD gene’s 72nd exon, disrupting protein production) was found. The variant came from her mother, who had no symptoms and normal CK (136.4 IU/L). Her maternal grandmother did not carry the variant.
This combination is rare because DMD is typically X-linked recessive: males inherit one X from their mother, so a single faulty DMD gene causes disease. Females have two X chromosomes—usually, a healthy gene on the second X protects them. But in TS, females have only one X—removing that “backup,” allowing the inherited DMD variant to cause disease.
Balancing Treatments for Two Conditions
Managing both TS and DMD required a multidisciplinary approach:
- TS: Growth hormone (GH) is recommended early to boost height. The team used PEG-GH (polyethylene glycol-bound recombinant human GH) at 0.2 mg/kg/week—starting at 9.5 years (later than the ideal 4–6-year window, but still within the 12–13-year cutoff for TS GH use).
- DMD: Coenzyme Q10 (a supplement to support muscle health) and neurologist-guided physical rehab (ankle/knee stretching) to preserve mobility.
After one year, results were promising:
- TS: She grew 4.8 cm (to 115.8 cm, -3.86 SD). Insulin-like growth factor-1 (IGF-1)—a GH-related hormone—increased from 240 mg/L to 403 mg/L (normal: 88–452 mg/L).
- DMD: Muscle weakness and Gowers’ sign didn’t worsen—a positive sign, as DMD typically progresses. However, CK remained high (6478 IU/L), and liver enzymes (AST, ALT) were slightly elevated (common in DMD due to muscle damage).
Why This Case Matters
TS affects 1 in 2000 females; DMD affects 1 in 4560 males in China. Since 1965, only seven other TS+DMD cases have been reported—3 with 45,X, 2 with mosaic TS (45,X/46,XX), and 2 with an incomplete X chromosome (46,X,i(X)(q10)).
Challenges remain:
- TS: GH worked for height, but the ideal start is 4–6 years (this patient started at 9.5).
- DMD: There’s little data on GH safety in DMD. The patient’s DMD symptoms didn’t progress in a year, but long-term outcomes are unknown.
- Emotional: Her parents are understandably anxious about prognosis and reproductive counseling (TS patients are usually infertile).
The Bigger Picture: Recognizing Multiple Genetic Disorders
Historically, doctors might have blamed multisystem symptoms on one disorder. But better genetic tools now reveal complex causes—like this TS+DMD case. Atypical symptoms (e.g., the girl’s strabismus) shouldn’t be dismissed as “part of TS”—they might signal a second condition.
This case highlights the need for:
- Thorough genetic testing for patients with unusual symptoms.
- Multidisciplinary care (endocrinologists, neurologists, rehab specialists) to address both conditions.
- Early intervention (like GH for TS) to improve quality of life.
Looking Ahead
While there’s no cure for TS or DMD, this patient’s journey shows that personalized care can make a difference. She gained 4.8 cm in a year, and her DMD symptoms stayed stable. For her family, the diagnosis brought clarity—even amid uncertainty.
The original study was published in the Chinese Medical Journal in 2021 by Jia-Jia Chen, Bing-Yan Cao, Chang Su, Min Liu, Di Wu, Wen-Jing Li, and Chun-Xiu Gong.
The full study is available at doi.org/10.1097/CM9.0000000000001159
Was this helpful?
0 / 0