u/Appropriate_Let631

Hi everyone,

Looking for input on outcomes for deletions involving the 5q35.2–q35.3 region including the NSD1 gene (Sotos syndrome confirmed).

A recurrent pathogenic deletion of approximately 1.8–2 Mb in this region (arr[GRCh37] 5q35.2–q35.3), where NSD1 is fully deleted and no additional CNVs are present, appears to be associated with a wide range of developmental outcomes.

There seems to be notable variability in motor development, language acquisition, and cognitive function across cases.

From a research and clinical genetics perspective, I’m curious about:

* Are there known modifiers (genetic, environmental, or epigenetic) that help explain variability in cognitive outcomes in NSD1 deletion cases? * Are there early developmental markers (e.g. motor, social, or attentional patterns in infancy) that correlate with later cognitive trajectories in Sotos syndrome? * Beyond NSD1, are there other genes in the 5q35.2–q35.3 region that are thought to meaningfully influence phenotype when co-deleted? * What does current evidence suggest about the impact of early intervention on developmental trajectories in overgrowth syndromes like Sotos? * Are there ongoing research efforts, registries, or longitudinal studies focused on NSD1 deletions that would be worth following?

I’m particularly interested in insights grounded in published data or clinical experience.

Thanks in advance.

Hi everyone,

I’m looking for insight from people familiar with 5q35 deletions / Sotos syndrome, especially cases involving NSD1 deletions.

Our daughter is 4 months old and has a confirmed pathogenic deletion:

* arr[GRCh37] 5q35.2–q35.3 (175,570,678–177,437,651) x1 * ~1.87 Mb deletion including NSD1 * No other CNVs identified

She has been diagnosed with Sotos syndrome.

What’s making this harder to interpret is that right now, she seems to be developing quite well:

* Cooing back and forth socially

* Smiling and engaging

* Good head control during tummy time

* Rolled from tummy to back

* Reaching for and grabbing objects

* Showing clear interest in her surroundings

* Strong anti-gravity movements

Physically, she is showing some Sotos features, but developmentally she doesn’t seem obviously delayed at this stage.

From what I’ve read, outcomes with NSD1 deletions can vary a lot. Some individuals have significant intellectual disability, while others seem to function much more independently.

I’m trying to understand what we can realistically expect and what we can do now to give her the best possible outcome.

Questions:

1. At this age (around 4 months), are there early signs that actually correlate with later cognitive outcomes in Sotos—especially for deletions?
2. Have you seen cases of children with full NSD1 deletions who track relatively well cognitively long-term?
3. Does early “typical” development at this stage tend to persist, or can gaps widen later?
4. What early interventions have made the biggest difference in real cases (PT, OT, speech, specific developmental models)?
5. Are there any medications, supplements, or emerging therapies (even experimental or adjacent fields like neuroplasticity research) worth looking into?
6. Are there any clinical trials, registries, or researchers (Canada/US) that families like ours should connect with early?

We’re already planning to pursue early intervention as much as possible, but we want to be as proactive and informed as we can.

I really appreciate any insights, whether clinical, research-based, or personal experience.

Thank you.

Hi everyone,

Looking for input on outcomes for deletions involving the 5q35.2–q35.3 region including the NSD1 gene (Sotos syndrome confirmed).

A recurrent pathogenic deletion of approximately 1.8–2 Mb in this region (arr[GRCh37] 5q35.2–q35.3), where NSD1 is fully deleted and no additional CNVs are present, appears to be associated with a wide range of developmental outcomes.

There seems to be notable variability in motor development, language acquisition, and cognitive function across cases.

From a research and clinical genetics perspective, I’m curious about:

* Are there known modifiers (genetic, environmental, or epigenetic) that help explain variability in cognitive outcomes in NSD1 deletion cases? * Are there early developmental markers (e.g. motor, social, or attentional patterns in infancy) that correlate with later cognitive trajectories in Sotos syndrome? * Beyond NSD1, are there other genes in the 5q35.2–q35.3 region that are thought to meaningfully influence phenotype when co-deleted? * What does current evidence suggest about the impact of early intervention on developmental trajectories in overgrowth syndromes like Sotos? * Are there ongoing research efforts, registries, or longitudinal studies focused on NSD1 deletions that would be worth following?

I’m particularly interested in insights grounded in published data or clinical experience.

Thanks in advance.