Children’s Clumsiness or Trusting Your “Parental Instinct”

Children often trip or fall during their process of learning to walk and which is totally normal since their balance and coordination skills are still in an early developmental stage. However, parents may notice that some children present several struggles for running, climbing stairs, getting up from the floor, or jumping which are often overlooked as motoric developmental delays, leading to underprioritized therapy and giving them additional time to develop their motoric skills as they grow older. Sadly, not all children’s mobility impairment are due to developmental delays since they can be a sign of muscle weakness disorders requiring early checkup.

The Tale of Two Systems: Nerves vs Muscles

Several types of diseases correlate with muscle weakness which might lead clinicians to misdiagnose them interchangeably, for example:

• Spinal Muscular Atrophy (SMA) – The “Wiring” Problem:
  • Imagine the brain is a power plant and the muscles are lightbulbs. Patient with SMA, the wires (nerves in the spine) are not working well. Because the signal can’t reach the bulb, the muscle stays “dark” and eventually shrinks (atrophies).
  • What to look for: A “floppy” child or a child who can sit but never stand. Muscle fatigue spread from lower body to upper body. Frequent falls increase with age.
• Duchenne Muscular Dystrophy (DMD) – The “Bulb” Problem:
  • The wires (nerves) are perfect, but the lightbulbs (muscles) are fragile. They are missing a “protective shock absorber” protein called Dystrophin. Every time the muscle works, it gets a bit damaged until it can no longer function.
  • What to look for: Large but weak calf muscles (Pseudohypertrophy), toe walking, frequent falls, and the “Gowers’ Sign”, using hands to “climb up” their own body to stand up.
• Limb Girdle Muscular Dystrophy (LGMD) – The “Hinges” (The Shoulders and Hips) Problem:
  • The hinges muscles are weak so other muscles cannot move freely because of heterogenous mutations.
  • What to look for: A “waddling” child with difficulty rising from a seated position and climbing stairs, toe walking, frequent falls, and pseudo hypertrophy of the calf. They can also face difficulties in stretching their arms or carrying heavy objects.

All of these muscular diseases can be misdiagnosed by doctors when only looking through clinical symptoms.

Why the “Traditional Way” of Testing is Stressful

Diagnosis for muscle dystrophies are usually performed through muscle biopsy which is invasive, causing discomfort for patients, or can produce a false negative result when there is sampling error. Targeted genetic testing can serve as an alternative approach for invasive testing if the diagnosis from clinical features by the doctor is highly reliable. However, since muscle weakness is associated with different types of disorders including heterogenous disease, guessing the suitable targeted genetic testing can be costly, inconclusive, and inefficient when trying different methods of diagnosis, extending the patient’s diagnostic journey.

How Genetic Testing Changes the Game

Hence, genetic testing using Clinical Whole Exome Sequencing (WES) represents the current diagnostic golden standard, providing diagnostic certainty and enabling informed, long-term clinical planning for affected individuals and their families. It proofreads every instruction manual of all 20,000 genes at once to find each single typo. The accurate diagnosis through a single blood draw can help patients and doctors to find the suitable treatment through:

• Targeted Therapy: Precision treatments like gene therapy only work if we know the exact mutation.
• Stopping the Guesswork: It ends the “trial-and-error” of ineffective invasive diagnostic procedures and physical therapies or medications.
• Family Planning: It helps parents understand the risk for future children or siblings.

NGI provides comprehensive Clinical Whole Exome Sequencing (cWES) and an even more detailed assessment of Clinical Whole Genome Sequencing (cWGS) services to help patients and healthcare providers gain a precise diagnosis through understanding the genetic cause behind complex or multisymptomatic diseases. These services can help prevent misdiagnosis merely based on clinical symptoms.

References:

1. Cleveland Clinic. 2023. “Limb-Girdle Muscular Dystrophy (LGMD).” Cleveland Clinic. December 12, 2023. https://my.clevelandclinic.org/health/diseases/limb-girdle-muscular-dystrophy-lgmd.
2. Dobrescu, M. A., G. Chelu, D. E. Tache, S. O. Purcaru, and I. O. Petrescu. 2015. “Differential Diagnosis between Duchenne Muscular Dystrophy and Limb Girdle Muscular Dystrophy 2a.” Current Health Sciences Journal 41 (4): 385–89. https://doi.org/10.12865/CHSJ.41.04.15.
3. Laverty, Chamindra . 2015. “Limb-Girdle Muscular Dystrophy (LGMD) – Signs and Symptoms | Muscular Dystrophy Association.” Muscular Dystrophy Association. December 18, 2015. https://www.mda.org/disease/limb-girdle-muscular-dystrophy/signs-and-symptoms.
4. Lim J, Eftimov F, Raaphorst J, Aronica E, van der Kooi AJ.2019. “Diagnostic value of additional histopathological fascia examination in idiopathic inflammatory myopathies.” Eur J Neurol.;26(12):1494-1496. doi: 10.1111/ene.14027. Epub 2019 Jul 18. PMID: 31220379; PMCID: PMC6916207.
5. Salort-Campana, E., and S. Quijano-Roy. 2020. “Clinical Features of Spinal Muscular Atrophy (SMA) Type 3 (Kugelberg-Welander Disease).” Archives de Pédiatrie 27 (7): 7S23–28. https://doi.org/10.1016/s0929-693x(20)30273-6.