Family Walking On the Beach

What Is SKS (or MINDS)? What is mTOR?

Smith Kingsmore Syndrome, also known as MINDS (Macrocephaly-Intellectual disability-Neurodevelopmental Disorder-Small thorax syndrome)

Finding out that your child has a rare disease is devastating, but we need to stay focused on what we can do now and what's ahead of us.

Although SKS presents a variety of tough symptoms to cure, there are things we can do now and in the future.  Here is the big picture I see.

 
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 1. Name, Symptoms, Prognosis

*Citation and links are coming later.  **My observation

Smith Kingsmore Syndrome is a rare neurological disorder mainly characterized by large head (macrocephaly), intellectual disability and (or) seizures.  It was only recently named, but so far, patients are found in up to age 30s.  It is caused by mutation of mTOR gene, usually resulting in "overactive" mTOR, affecting many cell functions.  MTOR gene has many variants under some subcategories, and a set of symptoms and severity vary, even within the same variant**.

The definition of the syndrome for the mTOR mutation or its subcategories might need some clarification in the future.

 

On my web site, for convenience, I talk about mTOR mutations resulting in overactive mTOR in general. On top of medical articles, I'm including updates of the general idea I get from talking and meeting other parents and patients.   

More accurate updated data is currently being collected through the registry set up by the excellent members of SKS Foundation, Dr. Carlos Prada and Cincinnati Children's Hospital.  

If you are a patient, please join the registry to support their effort to understand this rare disease.  This will also help setting up the universal coding of symptoms (IDC10/11) and find more patients.

Although mTOR has many functions in our body, most of problematic symptoms are neurological, behavioral and developmental issues.  It also seem to affect metabolism and sleep (circadian clocks) in some cases.

The most common features seems to be large head, intellectual disability and autism spectrum disorder (impaired communication and social interaction).  Overgrowth of head starts before or after birth and together with overgrowth of body, it usually slows down around age 5.  (That's why I wanted Elizabeth to try Rapamycin as soon as possible.) Body size seems to become average as they grow. 

 

Autism might start earlier in life and when it starts, language and social skills might regress.  Some of their stemming is a little different from typical Autistic stimming.  Applied Behavior Analysis Therapy (ABA Therapy) has been very helpful to Elizabeth.   

Common symptoms are epilepsy, behavioral conditions of attention-deficit/hyperactivity disorder ADHD, sleep issueslow muscle tone, flexible joints, club feet, a strange way of walking, curly hair, and special facial features.  Some starts epilepsy as infants, toddlers or teenagers, but others don't have it at all.  Epilepsy level can be mild or very hard to manage. 

Other common feature is brain abnormality. 

Examples are hemimegalencephaly or megalencephaly (one or both sides of the brain may be enlarged),  Polymicrogyria (too many wrinkles), and ventriculomegaly, ( the fluid-filled spaces near the center of the brain may be bigger than normal), less white matter in brain (hypomyelination).

Elizabeth has less common brain abnormality such as less white matter of brain, malformation of corpus callosum (mid divider part of brain), hydrocephalus (It's similar to ventriculomegaly, but evidence of intracranial pressure was found by ophthalmologists and some tests), etc.,

Other issues are: swallowing difficulty, small thorax, tongue tie, elevated optic nerve without intracranial pressure, fail to thrive (undergrowth), etc.   

 

Symptoms to be Cautious:  Uncontrolled Epileps, pneumonia caused by swallow problem and aspiration of food and drink, low blood glucose level.  Although mTOR mutation is one of the common genetic mutation in cancer cells and well studied in oncology, there seem to be no need to worry about cancer for SKS patients.

Elizabeth's mTOR variation might not exactly fit in the current definition of SKS. 

 

Dr. Mirzaa has categorized many mTOR variants, mainly by brain abnormalities and intellectual disability levels (*2019).

 

About 20 SKS families met in Cincinnati in 2019, and data was collected by Dr. Prada.   

 

A large portion of SKS patients belong to one variant, and  its symptom sets are described in Dr. Kate-Tatton's article. (2021*)

The second largest group includes two Mosaic variants, and one of them is Elizabeth's.  The details of her variant are in Dr. Mirzaa's 2 articles (*)and her case study by a team of Undiagnosed Diseases Network.(*2018)

 

Most other variant have 1-2 each patients diagnosed, but more and more patients are diagnosed these days.

In rare cases, mTOR is under-activated, causing small head and short height, but it also causes intellectual disabilities. (Dr. Prada) 

See Description of SKS at Med Line Plus of National Institute of Health 

https://medlineplus.gov/genetics/condition/smith-kingsmore-syndrome/#description

Many people with Smith-Kingsmore syndrome have unusual facial features, such as a triangular face with a pointed chin, a protruding forehead (frontal bossing), widely spaced eyes (hypertelorism) with outside corners that point downward (downslanting palpebral fissures), a flat nasal bridge, or a long space between the nose and upper lip (long philtrum). However, not everyone with Smith-Kingsmore syndrome has distinctive facial features.

Brain

*Citation and links are coming later.  **My observation

Smith Kingsmore Syndrome is a rare neurological disorder mainly characterized by large head (macrocephaly), intellectual disability and (or) seizures.  It was only recently named, but so far, patients are found in up to age 30s.  It is caused by mutation of mTOR gene, usually resulting in "overactive" mTOR, affecting many cell functions.  MTOR gene has many variants under some subcategories, and a set of symptoms and severity vary, even within the same variant**.

*Citation and links are coming later.  **My observation

Smith Kingsmore Syndrome is a rare neurological disorder mainly characterized by large head (macrocephaly), intellectual disability and (or) seizures.  It was only recently named, but so far, patients are found in up to age 30s.  It is caused by mutation of mTOR gene, usually resulting in "overactive" mTOR, affecting many cell functions.  MTOR gene has many variants under some subcategories, and a set of symptoms and severity vary, even within the same variant**.

 
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2. mTOR
Homeopathic Medicine
3. mTORC1 and mTORC2

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DNA
4. Network of Signaling Pathways

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Pipetting Samples and Test Tube
5.    

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