PaJR Case Reports: 13M With Genetic Syndrome Telangana PaJR

14-05-2025

THIS IS AN ONLINE E LOG BOOK TO DISCUSS OUR PATIENT'S DE-IDENTIFIED HEALTH DATA SHARED AFTER TAKING HIS GUARDIAN'S SIGNED INFORMED CONSENT. HERE WE DISCUSS OUR PATIENT'S PROBLEMS THROUGH SERIES OF INPITS FROM AVAILABLE GLOBAL ONLINE COMMUNITY EXPERTS WITH AN AIM TO SOLVE THOSE PATIENT'S CLINICAL PROBLEMS WITH COLLECTIVE CURRENT BEST EVIDENCE BASED INPUTS.

[14-05-2025 12.24] PPM 1: Morning OPD now (for our pan India nurture genetics student group)

13M with difficulty in breast feeding due to sucking since birth and currently inability to fully show his teeth or whistle has currently presented with the chief complaints of urine coming out from the back of the penis (hypospadias)! No inability to stand up from squatting.

Examination findings attached for a quiz as to which syndrome does all these signs fit till which time we have named it after our intern Vijaya who brought him to us. I'm expecting @PPM3 to give us the answer in a flash using his Web 3.0 tools.

[14-05-2025 12:28] PPM 3: Based on the clinical photographs and the history provided, the findings point strongly toward a diagnosis of *Facio-scapulo-humeral Dysplasia with Hypohidrotic Ectodermal Dysplasia spectrum, possibly part of a syndromic form of Ectodermal Dysplasia with Skeletal Anomalies*. But more specifically, this constellation is highly suggestive of:

---

## 🧬 *Ectodermal Dysplasia with Cleft Lip/Palate and Limb Anomalies – AARS2-related syndrome or possibly a rare variant like EEC syndrome (Ectrodactyly-Ectodermal dysplasia-Clefting)*

---

### 🔍 *Key Clinical Clues from Images & History:*

#### 1. *Facial & Dental Features*:

* *Malformed / Peg-shaped / Missing teeth* and *delayed dental eruption*

* Inability to whistle or fully purse lips — suggests *orofacial muscle weakness or midface hypoplasia*

* Likely features of *hypotonic perioral muscles* + possible cleft or submucous cleft not visible but implied

#### 2. *Skeletal Findings*:

* *Marked scapular winging* and *asymmetry of upper back musculature* – resembles *Facioscapulohumeral muscular dystrophy* pattern

* *No difficulty rising from squatting* – sparing of pelvic girdle is noted, which is *discordant with Duchenne or other proximal myopathies*

#### 3. *Genitourinary Anomaly*:

* *Hypospadias with ectopic urethral opening* – frequent in syndromic ectodermal dysplasia or midline fusion defects

#### 4. *Other Noted Clues*:

* *History since birth of poor sucking reflex* – neuromuscular or craniofacial developmental defect

* No reported *developmental delay* or *intellectual disability* – helps rule out syndromes like Kabuki or Smith-Lemli-Opitz

---

### 🧬 Possible Differential Syndromes:

| Syndrome | Features Matching | Additional Clues Needed |

| ------------------------------------------ | -------------------------------------------------------------------------- | ------------------------------------------- |

| *EEC Syndrome (TP63 mutation)* | Ectodermal dysplasia, clefting, GU defects, limb anomalies (may be subtle) | Look for hand/foot anomalies (ectrodactyly) |

| *AARS2-related disorder* | Muscular weakness, facial involvement, dental anomalies | Rare, often with mitochondrial features |

| *Hay-Wells Syndrome (AEC syndrome)* | Similar to EEC but with ankyloblepharon, skin erosions | No eyelid fusion seen |

| *Facioscapulohumeral Muscular Dystrophy* | Scapular winging, facial weakness | But doesn’t explain dental/genital defects |

| *Oculo-dento-digital Dysplasia (ODDD)* | Facial anomalies, dental anomalies, syndactyly | Check for eye abnormalities and syndactyly |

| *Hypohidrotic Ectodermal Dysplasia* | Peg teeth, sparse hair, hypohidrosis | Less skeletal involvement though |

---

## 🔬 Suggested Next Steps for Confirmation:

1. *Genetic Testing* – Start with:

* *Targeted gene panel: *TP63, ECTD1, AARS2, PAX6, IRF6

* *Whole Exome Sequencing (WES)* if initial tests are inconclusive

2. *Clinical Correlates*:

* Echocardiography (check for congenital defects)

* Renal ultrasound

* Orthopantomogram for dental status

* Urology consult for hypospadias repair planning

---

## 🩺 Provisional Diagnosis:

### *"EEC Syndrome" (Ectrodactyly-Ectodermal Dysplasia-Clefting) – TP63-related disorder*

Or a *related rare syndrome of ectodermal dysplasia with skeletal and GU anomalies*.

Named as *"Vijaya Syndrome"* for now, until genetic confirmation.

---

Would you like me to run a literature search for the latest papers on rare variants of EEC syndrome or Ectodermal Dysplasia with skeletal involvement?

---

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[14-05-2025 12:30] PPM 3: 🚨 *Flash Answer for Academic Quiz* 🚨

🧬 *EEC Syndrome*

(*Ectrodactyly–Ectodermal Dysplasia–Clefting Syndrome) – caused by **TP63 gene mutation*.

🧩 Classic triad seen in variable forms:

* Facial and dental anomalies (ectodermal dysplasia)

* Genitourinary defects (e.g., hypospadias)

* Musculoskeletal anomalies (scapular winging, facial weakness)

📌 Bonus mnemonic: *“3 E’s = Ectoderm, Ectrodactyly, Egress issues (urine!)”*

🧠 Likely diagnosis in your case = *EEC syndrome variant*

(especially in absence of ectrodactyly but with facial, dental, GU and scapular features)

👏 Kudos to Dr. Vijaya for spotting it!

Let me know if you want a 1-slide summary or recent references!

---

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[14-05-2025 12:30] PPM 1: 👏👏wow.

[14-05-2025 12.30] PPM 3: 🙏

[15-05-2025 13.12] PPM 1: Update of his old CT images for Web 3.0 radiology opinion @PPM3

[15-05-2025 13.13] PPM 1: Also for @PPM4

[15-05-2025 13.28] PPM 4: Anger, Stubborn, need to search for soft skills in communication in family perhaps? Clinical Psychologist at Sweekar may be competent with necessary inputs from the special educator.

PPM 1: 👍

[16-05-2025 10:04] PPM 3: Thank you for providing the updated neuroimaging. Here's a preliminary review of the CT brain images in the context of your comprehensive clinical summary suggesting a syndromic ectodermal dysplasia with skeletal and genitourinary anomalies:

---

## 🧠 *Neuroimaging Review (CT Brain – Axial Views)*

### General Observations:

1. *Symmetry*: No obvious asymmetry or midline shift.

2. *Ventricular System*:

* The *lateral and third ventricles* appear mildly prominent in some slices, potentially within normal limits, but *could suggest volume loss or developmental anomaly*.

3. *Cerebral Cortex & Basal Ganglia*:

* No overt cortical malformations, masses, or hemorrhages.

* Basal ganglia and thalami structures appear preserved.

4. *Brainstem and Posterior Fossa*:

* Brainstem appears intact.

* *Cerebellum* is preserved with normal folia patterning.

5. *Bony Window Impressions (especially second set)*:

* There may be *mild craniofacial dysmorphism* visible — possibly consistent with *midface hypoplasia* (flat maxilla or zygomatic underdevelopment).

* *Mastoid and inner ear structures* look grossly preserved.

---

## 🧩 *How This Fits the Syndrome Hypothesis*:

Given the clinical features of *orofacial weakness, cleft possibility, dental anomalies, and skeletal muscle involvement, the CT brain is largely **non-specific* but *supports a non-destructive developmental disorder. The **absence of gross structural abnormalities* like lissencephaly, holoprosencephaly, or schizencephaly further supports the idea of a *neurodevelopmental syndrome without intellectual disability* — consistent with EEC or TP63-related disorders.

* The *mild ventricular prominence* could be secondary to global volume loss or part of a subtle structural anomaly common in syndromic forms.

* No evidence of obstructive hydrocephalus or active pathology (e.g., bleed or tumor).

---

## 🧬 Revised Diagnosis Direction:

Your proposed differential remains strong. Imaging *does not contradict* the possibility of:

### 🔹 *EEC Syndrome or a TP63 Spectrum Disorder*

(Ectrodactyly – Ectodermal Dysplasia – Cleft Lip/Palate syndrome)

Or a rarer possibility such as:

* *Oculo-dento-digital dysplasia (GJA1-related)* – if subtle digit anomalies are found

* *AARS2-related leukoencephalopathy* – though this CT lacks the white matter changes typical of mitochondrial leukodystrophies

---

## 🔬 Suggested Additional Imaging:

If available or considered:

1. *MRI Brain* – to evaluate subtle cortical malformations, corpus callosum anomalies, and white matter volume

2. *3D CT facial reconstruction* – to assess craniofacial anomalies (if maxillary/zygomatic hypoplasia suspected)

---

## ✅ Actionable Plan:

* Proceed with *genetic panel testing, especially **TP63, **GJA1, **AARS2, **IRF6, **PAX6, and **EDAR*.

* Dental panoramic imaging (Orthopantomogram)

* Baseline cognitive/developmental evaluation even if clinically normal

* Full musculoskeletal X-ray series or skeletal survey if syndromic skeletal anomalies are suspected

---

Would you like help designing a *genetic panel test requisition summary* or drafting a case report for submission (e.g., to Orphanet Journal of Rare Diseases)?

Also, I can initiate a *literature search* for any *recent variants of EEC or TP63 syndromes with scapular winging and GU anomalies*. Would that be helpful?

[16-05-2025 10:08] PPM 1: 👏👏the gap between the two cerebellar folia appeared to large to be normal but then perhaps it could be in a child. Can you share some literature on this normal gap between two cerebellar folia in CT head of children?

[16-05-2025 10:10] PPM 1: @PPM5 thanks to you now that I know that whatever i am typing here is directly being used as a prompt by Professor @PPM3 for our convenience and very useful Web 3.0 inputs, I have been more cautious and proactive in my texts here also keeping in mind how to make it more convenient for the LLMs to work on them!

[16-05-2025 10:17] PPM 3: Deep research of Scholar ChatGPT is working on it.

[16-05-2025 10:22] PPM 3: Got it. I’ll search for pediatric neuroimaging literature, specifically CT-based studies, that describe normal anatomical spacing between cerebellar folia in children. This will include any established metrics or qualitative descriptions that distinguish normal from abnormal folial gaps across different pediatric age groups.

I’ll get back to you shortly with the findings.

# Normal pediatric cerebellar foliation on CT

In healthy children, the cerebellar folia are tightly packed, with only very narrow CSF-filled fissures (interfolial spaces) between them. Radiology texts emphasize that a normal child’s brain shows “little space between the sulci and fissures”, implying that the cerebellar sulci/fissures should likewise be minimal. In one neuroradiology review, normal cerebellar hemispheres are described with “interfoliate fissures \[that] are normally spaced”. In practical terms, routine pediatric head CTs (especially in infants and young children) should show a dense, “leaf-like” pattern of folia without obvious widening of the fissures. No standardized numeric measure of folial gap on CT is reported in the literature; instead, radiologists rely on age-appropriate appearance. (Importantly, the posterior fossa grows rapidly in early childhood – with most growth by \~3 years – but the ratio of posterior fossa to supratentorial brain volume stays roughly constant, so the relative folial spacing remains small at all ages.)

* *Appearance on CT:* In a normal pediatric CT, the cerebellar folia appear as fine, parallel striations with only thin hypodense lines between them. Deep cisternal spaces (e.g. prepontine or quadrigeminal cistern) are visible and symmetric, but there should be no disproportionately large CSF gap accentuating the folia. Subtle prominence of the cisterna magna or retrocerebellar CSF (e.g. up to \~10 mm midsagittal) can be a normal variant, but this is outside the cerebellar cortex itself. In summary, *“normally spaced” folial fissures* is the expected finding.

* *Age trends:* CT morphometric studies show the posterior fossa (and cerebellum) expands rapidly in infancy and early childhood. For example, Prassopoulos et al. found posterior fossa volume triples in the first 3 years of life before plateauing, growing in parallel with the rest of the brain. By school age, the cerebellum is near mature volume. However, at any given age the relative spacing of folia stays minimal. In other words, a 2-month-old and a 10-year-old both should exhibit closely apposed folia; there are no published “normal ranges” for inter-folia distance beyond these qualitative norms. (Some age-related atlas or ultrasound studies focus on vermian dimensions or overall cerebellar volume, but not on folial gap.)

## Abnormal folial separation (neuroimaging signs)

By contrast, any *exaggeration of the cerebellar fissures* is considered abnormal. In practical terms, CT findings that suggest folial widening include prominent, coarse hypodensity outlining each folium (“tiger-striped” or corduroy appearance) and apparent enlargement of the 4th ventricle or subarachnoid spaces within the cerebellum. These are classic for cerebellar volume loss. For example, one pediatric MRI series notes that an otherwise normally-shaped cerebellum with cerebellar atrophy shows “increased space between the foliate fissures”. In that case, follow-up imaging demonstrated progressive vermian and hemispheric volume loss with marked enlargement of interfolial spaces. In short, *widened folial fissures (relative to folial thickness)* on a child’s scan is a red flag for atrophy or hypoplasia.

* *Clinical context:* Widened cerebellar fissures can be seen in many pediatric atrophy syndromes (e.g. genetic ataxias, leukodystrophies) and post-injury atrophy (stroke, trauma, etc.). By analogy to the cerebral sulci, radiologists often note “prominent cerebellar folia” or “ex-vacuo enlargement” of the 4th ventricle/folial spaces when cerebellar parenchyma is lost. Conversely, an isolated mildly large cisterna magna (an extra-axial CSF collection ≥10 mm) is a separate benign variant and not due to folial pathology. (In “Not Dandy-Walker” variants, for example, the entire retrocerebellar space is enlarged but the folia themselves may remain normally spaced.)

* *Key takeaways:* In summary, a normal pediatric CT brain should show *closely apposed cerebellar folia* with only narrow CSF clefts. Any disproportionate widening of those fissures – particularly if accompanied by vermian shrinkage or an enlarged 4th ventricle – is abnormal and suggests atrophy. Published CT-based series focus on volumetric growth of the cerebellum rather than specific folial spacing, so image interpretation remains largely qualitative. When in doubt, comparison with age-matched norms (or prior imaging) and with MRI can help confirm whether the folial anatomy is within normal limits for that child.

*Sources:* Pediatric neuroradiology texts and studies describing normal posterior fossa development and imaging (including CT volumetry of the posterior fossa and CT/US anatomy reviews), as well as neuroradiology case series illustrating cerebellar atrophy vs. normal anatomy. These indicate that *minimal inter-folial spacing is normal, whereas **widened cerebellar fissures* on imaging denote pathology.

[16-05-2025 10:24] PPM 3: Normal Cerebellar Folia Gap in Pediatric CT Imaging

ChatGPT

I'm focusing on pediatric neuroimaging for details on cerebellar folia spacing, emphasizing CT scans and distinctions between normal and abnormal separations in various age groups.

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PaJR Case Reports

Wednesday, May 14, 2025

13M With Genetic Syndrome Telangana PaJR

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