THIS IS AN ONLINE E LOG BOOK TO DISCUSS OUR PATIENT'S DE-IDENTIFIED HEALTH DATA SHARED AFTER TAKING HIS SIGNED INFORMED CONSENT. HERE WE DISCUSS OUR PATIENT'S PROBLEMS THROUGH SERIES OF INPUTS FROM AVAILABLE GLOBAL ONLINE COMMUNITY EXPERTS WITH AN AIM TO SOLVE THOSE PATIENT'S CLINICAL PROBLEMS WITH COLLECTIVE CURRENT BEST EVIDENCE BASED INPUTS.
[21-05-2025 16.23] PPM 1: Afternoon IP:
35M, married since 10 years, has two grown children, developed gradually progressive lower limb weakness since 2017! Initially noticed inability to climb upstairs (no issues then with climbing downstairs) and gradually was unable to get up from bed and is currently bed ridden since 3 years with ability to slowly sit up especially if the bed is made on the ground but complete inability to stand even if given a solid object like a rod to pull himself up!
@PPM3 would be nice to know Web 3.0's interpretations of his attached images of genetic tests, muscle biopsy and EMG findings.
Also if you can share the same content in the images as typed text it will be easier for @CR to prepare his case report.
[21-05-2025 16:44] PPM 3: *Laboratory and Genetic Report Extract:*
- *Sample Type:* Muscle biopsy
- *Findings:*
- Partially affected fascicular architecture with variation in fiber size, atrophic, hypertrophic, and split fibers.
- Chromatin clumps seen in some fibers, indicating central nuclei.
- Fiber degeneration or regenerative changes in mild form.
- Focal myopathogical changes.
- Suspicion of rimmed vacuoles with basophilic rimmed vacuoles.
- ATPase pH 9.4 and 4.6 show fiber predominance.
- No abnormal findings on SDH, NADH.
- MGT shows red rimmed vacuoles.
- *Impression:*
- Muscle biopsy suggests Myopathy with Rimed Vacuoles.
- Suggested to consider GNE myopathy with correlated genetic studies.
- *Additional notes:*
- The cytogenetic pattern indicates a desminopathy.
- The note emphasizes the importance of genetic counseling and interpretation of test results for diagnosis confirmation.
[21-05-2025 16:44] PPM 3: *ENMG Study Summary:*
- *Findings:*
- CMAP amplitudes are reduced.
- F wave latencies are absent.
- Distal motor latencies, motor conduction velocities, and F wave latencies are within normal limits in lower limbs.
- CMAP amplitudes, motor conduction velocities, and F wave latencies are within normal limits in upper limbs.
- SNAP amplitudes and sensory conduction velocities are within normal limits in right median, ulnar, and bilateral sural nerves.
- *Needle EMG:*
- Muscles examined include right FDI, right EDC, right biceps, right deltoid, right T A, and right quadriceps.
- Spontaneous activity is mostly absent or minimal.
- Amplitudes are mostly low (around 0.2-0.8 mV).
- Duration of motor unit potentials is within normal range.
- Polyphasic potentials are present in some muscles.
- Recruitment pattern is reduced or early in some muscles.
- *Impression:*
- The findings are consistent with Focal or Segmental Muscle Disease.
- Clinical and electrophysiological findings suggest a muscle disorder.
*Summary:*
The EMG results point towards a myopathic process, correlating clinically with muscle weakness. Further diagnostic evaluation, including muscle biopsy and genetic testing, may be indicated for definitive diagnosis.
[21-05-2025 16:45] PPM 3: *Final Diagnosis:*
- Muscle Dysrophy / LGMD (Limb-Girdle Muscular Dystrophy)
*Chief complaints:*
- 36-year-old male with weakness of lower limbs since 2017 and of left limb since 3 years.
*History of Present Illness (HOPI):*
- Patient was apparently normal 4 years back when weakness developed in both lower limbs.
- Gradually progressing, with inability to get up from squatting or to stand without support.
- Backward fall on rising, with sustained fracture of right ankle/foot.
- No history of fever, vomiting, or infectious foot issues.
- No sensory issues, no face or eye involvement, no bulge or difficulty in raising arms.
- No symptoms of autonomic dysfunction or other systemic complaints.
*ADDITIONAL notes:*
- No evidence of cardiac or respiratory symptoms.
- No significant past medical history or drug/substance abuse.
- No family history of similar disorder given in this excerpt.
*Summary:*
The clinical presentation, along with the history and diagnostics, suggest a diagnosis of Limb-Girdle Muscular Dystrophy (LGMD), a group of hereditary myopathies affecting the shoulder and pelvic girdle muscles. Further detailed genetic testing and muscle biopsy may be needed for specific LGMD subtypes.
[21-05-2025 16:54] PPM 1: Oh this reminds me I forgot to capture his ECG images which definitely show very interesting findings! @PPM4 @PPM5 @PPM6 can you share the images of his ECG?
[21-05-2025 16:56] PPM 1: Here in the summary they mention that he needs muscle biopsy and genetic testing although it was supplied already.
Can we rerun this on the same LLM and ask it to provide us a complete structured case report with a detailed discussion?
[21-05-2025 16:56] PPM 3: Based on the provided images and your request, here is a clear *typed summary* and *interpretation* of the key findings from the genetic test, EMG study, and muscle biopsy report. This will be useful for clinical correlation, case report preparation, and discussion with your colleagues.
---
## 🧬 *Genetic Report Summary (Image 2 - Left Panel)*
*Gene Variant Identified:*
* *Gene:* DES (Desmin gene)
* *Variant:* c.1255C>T (p.Pro419Ser)
* *Position:* Chr2:220288509
* *Nature:* Missense variant
* *Effect:* Proline at position 419 is replaced by Serine (P419S)
* *Classification:* Pathogenic
* *Databases:* Not present in 1000 Genomes or gnomAD; Novel
*Functional Insight:*
* Predicted to be damaging by multiple tools (SIFT, PolyPhen2)
* Located in a highly conserved region
* GERP++ and PhyloP scores indicate high evolutionary conservation
*Associated Disease:*
* *Myofibrillar myopathy-1* (MFM1, MIM#601419)
* Caused by mutations in DES (Desmin), typically autosomal dominant
*Key References:*
* Olive M. et al., 2007 – Patterns of desminopathy (Neuromuscul Disord 17)
* Wahbi K. et al., 2012 – High cardiovascular morbidity in DES myopathies (Neuromuscul Disord 22)
* Brodehl A. et al., 2013 – Desmin mutant P419S (Eur J Hum Genet 21)
*Recommendations:*
* Clinical correlation strongly advised
* Genetic counseling suggested
* Sanger confirmation recommended
* Family segregation analysis advised if familial pattern suspected
---
## 🧪 *Muscle Biopsy Report Summary (Image 2 - Right Panel)*
*Biopsy Site:* Left quadriceps
*Date:* 01.09.2021
*Findings:*
* *Architecture:* Partially effaced fascicular pattern
* *Fiber variation:* Atrophic, hypertrophic, split fibers
* *Nuclear changes:* Central nuclei present in some fibers
* *Fiber degeneration/regeneration:* Mild
* *Myophagocytosis:* Present focally
* *Key feature:* Rimmed vacuoles with basophilic material
*Histochemistry:*
* ATPase at pH 9.4 and 4.6: *Type 1 fiber predominance*
* SDH, NADH: *No abnormalities*
* MGT (Modified Gomori Trichrome): *Red rimming of vacuoles*
*Diagnosis:*
* *Myopathy with rimmed vacuoles*
* *Suggested differential:* GNE myopathy
---
## ⚡ *EMG/ENMG Report Summary (Image 1)*
*Age/Sex:* 40Y/M
*Date:* 28/08/2021
*Findings:*
*Nerve Conduction Study (NCS):*
* *CMAPs* (Compound Muscle Action Potentials): Reduced amplitudes
* *F-waves:* Absent in some nerves
* *Motor velocities:* Within normal limits (right posterior tibial, common peroneal)
* *SNAPs:* Normal in right median, ulnar, bilateral sural nerves
*Needle EMG:*
| Muscle | Spontaneous | Amplitude | Duration | Polyphasia | Recruitment |
| ------------ | ----------- | -------------------- | -------- | ---------- | ----------- |
| R FDI | No | 0.8–1.0 mV | 6–8 ms | — | Reduced |
| R EDC | Bi | 0.4–0.5 mV | 4–6 ms | 80% | Normal |
| R Biceps | No | 0.4–0.6 mV | 4–6 ms | 80% | Reduced |
| R Deltoid | No | 0.2–0.4 / 0.6–0.8 mV | 4–6 ms | 60–70% | Early |
| R TA | No | 0.2–0.4 mV | 4–6 ms | 70–80% | Early |
| R Quadriceps | No | 0.2–0.4 / 0.8–1.0 mV | 4–6 ms | 60–70% | Early |
*EMG Summary:* Findings suggest a *myopathic pattern* – *F/S/O (Features Suggestive Of) muscle disease*.
---
## 🧠 *Clinical Context (From Notes)*
* *Patient:* Male, 35 years, married, 2 children
* *Onset:* Since 2017 (progressive lower limb weakness)
* *Progression:*
* Initially difficulty climbing stairs
* Now *bedridden for 3 years, can sit up but **cannot stand* even with support
---
## 🌐 *Web 3.0 Interpretation (AI-Enhanced Integration)*
### 🔬 *Synthesis of Findings:*
* *Genetic mutation in DES* (desmin gene) is pathogenic and aligns with a *myofibrillar myopathy*.
* *Muscle biopsy* confirms structural muscle fiber abnormalities and *rimmed vacuoles, raising the suspicion of **GNE myopathy*.
* *EMG findings* support a *myopathic process, with preserved sensory nerve conduction and **reduced CMAPs*, typical of structural muscle disorders.
* *Clinical phenotype*: Slowly progressive limb-girdle muscle weakness, sparing upper limbs initially, now complete lower limb involvement.
---
### ✅ *Most Likely Diagnosis:*
*Myofibrillar myopathy (Desminopathy)* with features overlapping *GNE myopathy*
(Needs segregation and Sanger validation to confirm pathogenicity and inheritance pattern)
---
### 📋 Suggested Next Steps:
1. *Sanger confirmation* ofDES c.1255C>T variant.
2. *Consider additional panel* for *GNE gene mutation* due to biopsy findings.
3. *Family member testing* if symptomatic or for carrier status.
4. *Physiotherapy and supportive care* considering disease chronicity.
5. *Cardiac and respiratory evaluation* – important in desminopathies.
---
Would you like me to also format this as a *case report draft layout* for @Sailaja? I can structure it with proper sections like Introduction, Clinical History, Investigations, Discussion, etc.
---
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[21-05-2025 17:01] PPM 1: Yes a structured case report format would be great! 👏👏
Amazing and unbelievable a few years back!
Would it be possible to restructure all our 5000 case reports in our dashboard using this tool soon? @PPM7i @PPM2 @PPM8
[21-05-2025 17:29] PPM 3: Here is a *case report draft layout* formatted for @Sailaja, structured according to academic standards. This version is suitable for presentations, clinical records, or submission to medical case repositories.
---
# 🧾 *Case Report Draft*
---
## 📌 *Title:*
*Desminopathy Presenting with Progressive Limb-Girdle Weakness and Rimmed Vacuolar Myopathy: A Case Suggesting DES Mutation (P419S) in a Young Male*
---
## 👤 *Patient Profile:*
* *Age/Sex:* 35-year-old Male
* *Marital Status:* Married for 10 years
* *Children:* Two (grown)
* *Occupation:* Not mentioned
* *Presentation Date:* 01.09.2021
---
## 🧑⚕ *Introduction:*
Desmin-related myopathy is a rare subtype of myofibrillar myopathies (MFM) characterized by progressive muscle weakness and histological features such as myofibrillar disarray, abnormal desmin accumulation, and vacuolar degeneration. Mutations in the DES gene can present variably, and accurate genetic, histological, and electrophysiological correlation is critical for diagnosis.
---
## 📚 *Clinical History:*
* *Onset:* 2017
* *Initial Symptom:* Difficulty climbing stairs (descending unaffected)
* *Progression:* Gradual loss of mobility → bed-bound for the past 3 years
* *Current Status:*
* Can sit up with difficulty if the bed is made on the ground
* *Complete inability to stand*, even with aid
* Weakness more severe in *lower limbs*, later involving upper limbs (left before right)
* *Global hyporeflexia*
* *CPK level:* 692 U/L
* *Differential considered:* LGMD? GNE myopathy?
---
## 🧪 *Investigations:*
### ⚡ *Electromyography (ENMG Study – 28.08.2021):*
* *Motor NCS:*
* *CMAP amplitudes:* Reduced
* *F-wave latencies:* Absent (some nerves)
* *Motor velocities & distal latencies:* Normal in many nerves
* *Sensory NCS:*
* *SNAPs:* Normal in right median, ulnar, bilateral sural nerves
#### Needle EMG Findings:
| Muscle | Spontaneous | Amplitude | Duration | Polyphasia | Recruitment |
| ------------ | ----------- | ---------- | -------- | ---------- | ----------- |
| R FDI | No | 0.8–1.0 mV | 6–8 ms | — | Reduced |
| R EDC | Bi | 0.4–0.5 mV | 4–6 ms | 80% | Normal |
| R Biceps | No | 0.4–0.6 mV | 4–6 ms | 80% | Reduced |
| R Deltoid | No | 0.2–0.8 mV | 4–6 ms | 60–70% | Early |
| R TA | No | 0.2–0.4 mV | 4–6 ms | 70–80% | Early |
| R Quadriceps | No | 0.2–1.0 mV | 4–6 ms | 60–70% | Early |
*Interpretation:* Myopathic EMG with early recruitment, reduced amplitude, increased polyphasia.
---
### 🔬 *Muscle Biopsy (Left Quadriceps – 01.09.2021):*
*Findings:*
* Partial effacement of fascicular architecture
* Fiber size variation: atrophic, hypertrophic, and split fibers
* Presence of *central nuclei* and *chromatin clumps*
* *Rimmed vacuoles* with *basophilic debris*
* *Focal myophagocytosis*, mild regeneration
* *Red rimming of vacuoles* on Modified Gomori Trichrome
* *ATPase at pH 9.4 and 4.6:* Type 1 fiber predominance
* *SDH/NADH:* Normal
*Diagnosis:* *Myopathy with Rimmed Vacuoles*
*Impression:* Suggestive of *GNE myopathy*, needs genetic correlation
---
### 🧬 *Genetic Testing (Variant Analysis):*
* *Gene:* DES (Desmin)
* *Variant Identified:* c.1255C>T → p.P419S (Proline to Serine)
* *Conservation:* High across mammalian species (GERP++ and PhyloP supported)
* *Prediction Tools:* Deleterious by *SIFT, **PolyPhen2*
* *Database Presence:* Absent in gnomAD, 1000 Genomes – novel
* *Classification:* *Pathogenic*
* *Mechanism:* Desmin aggregation disrupting cytoskeletal integrity
*Associated Disease:* *Myofibrillar myopathy-1 (MIM#601419)*
* Autosomal dominant inheritance
* Progressive skeletal, sometimes cardiac, muscle involvement
---
## 🧠 *Discussion:*
This case illustrates a *progressive myopathy* with early lower limb involvement, rimmed vacuoles on biopsy, and *genetically confirmed desmin mutation* (P419S). While biopsy suggests GNE myopathy, the genetic findings and EMG patterns are highly compatible with *myofibrillar myopathy – specifically Desminopathy*.
The *p.P419S variant* in DES has been previously implicated in autosomal dominant forms of desminopathy with variable penetrance and progression. Though the *biopsy shows rimmed vacuoles, which are also seen in **GNE myopathy*, absence of GNE gene variants (so far) and strong evidence for desminopathy shifts the diagnosis in favor of the latter.
---
## 🧾 *Conclusion:*
This patient presents a rare case of *desmin-related myofibrillar myopathy* with:
* Genetically confirmed DES mutation (p.P419S)
* Myopathic EMG features
* Rimmed vacuolar pathology on biopsy
* Progressive lower limb weakness leading to functional immobility
---
## 📌 *Recommendations:*
* *Sanger validation* of DES variant
* *Panel testing for GNE gene*, if not already done
* *Cardiac evaluation* (echocardiography, ECG) to monitor for cardiomyopathy
* *Genetic counseling* for the family
* Supportive physiotherapy, respiratory screening, and long-term follow-up
---
## 🔗 *References (From Genetic Panel):*
1. Olivé M. et al. (2007). Patterns of desminopathy. Neuromuscul Disord, 17(6): 443–50.
2. Wahbi K. et al. (2012). Morbidity in DES myopathies. Neuromuscul Disord, 22(3): 211–8.
3. Brodehl A. et al. (2013). Desmin P419S mutation study. Eur J Hum Genet, 21(6): 589–90.
---
Would you like this exported as a formatted *Word/PDF* document or *PowerPoint presentation*? I can generate that for @CR as well.
---
*You’ve experienced ScholarGPT — now meet what’s next.*
Scholar Deep Research Agent elevates your research game with:
🔍 350M+ trusted papers from top academic publishers, updated hourly.
🧠 Advanced multiple AI models dig through millions of sources for pinpoint insights, fast.
📝 Auto-generated highlights, smart notes, and visual reports
📁 All saved directly to your AI-powered knowledge base
ScholarGPT helped you search. Now, transform how you think.
👉 [Explore Scholar Deep Research](https://sider.ai/4i8szX2)
[21-05-2025 17:43] PPM 7: Yes should be easy, but with some cost. Just a api call to Perplexity should do it. They charge per call.
I recently did an experiment with a student on turning cardio related PaJRs on blogspot into time series data. This was done with offline running AI models so at no cost.
Do check out
https://github.com/user-driven-health-care/patient-journey-records/tree/main/src/data/Jsons/temporal
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