Syngap could have an ICD-10 code (F78.A1) as soon as next year

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The cover slide of Dr. Smith-Hicks, PhD, presentation to the CDC
The cover slide of Dr. Smith-Hicks, PhD, presentation to the CDC

Mike is the co-founder & Managing Director of SRF.

There is important news in this article.  We have quoted liberally, with links, from other articles in the interest of not reinventing anything and also to point you to other articles if you want to learn more.  The punchline is that Syngap is making considerable progress and once this is finalized you should share this information with your clinicians.

What is an ICD code?

Per Wikipedia, the “International Classification of Diseases (ICD) is the code used for the purpose of documenting a person’s medical condition. It is usually important for health insurance reimbursement, administration, epidemiology, and research. Of the approximately 7,000 rare diseases, only about 500 have a specific code. An ICD code is needed for a person’s medical records—it is important for health insurance reimbursement, administration, epidemiology, and research. Finding the best ICD code for a patient who has a rare disease can be a challenge.”  

The history of the ICD up to the 10th revision is laid out in a eight page article from the WHO.  ICD-10 is what is in use in the US today.  You may have also heard of ICD-11 and this is coming in 2022, per the WHO.  The US, however, generally takes a number of years, if not a decade to adopt a new ICD, so even though ICD-11 will be in use in the rest of the world, ICD-10 is what we should expect for the foreseeable future Stateside.

Why do they matter?

The Atlantic did a piece on ICD codes for Angelmans (Q93.51)  in 2018, please read it.   An article about why they matter from Pompe disease (E74.02) makes the point is “without a diagnostic code within the ICD-10 system, it’s very difficult to track how many people have that disease, where they are, and all the characteristics of the disease”.  As any member of the Syngap Community knows, just figuring out how many of us there are is a struggle.  SRF began a #SyngapCensus that has been supported by the Syngap Global Network who now sponsors a map as well.  These initiatives are important and consume many volunteer hours.  Once we have an ICD code, getting an accurate current count will be much easier.  That matters at least 1,000 cases in the US is the minimum threshold for many biotechs and drug companies to invest in a disease.

But a count is not the only reason these matter, it also facilitates health insurance reimbursement, administration, epidemiology, and research.  Not to mention, frankly, being taken seriously.  Almost every parent today has had an experience where a provider has learned about the disease and then had to Google it for themselves.  Followed by awkward conversations where the practitioner says how little is known and then the parent has to point them to key papers like Dr. Scheffer’s to learn about the disease. Once Syngap has an ICD code, frankly, practitioners are more likely to realize that they need to study up.

Does Syngap have one?

No.  Not yet.  But we are close.  Angelmans got one – Q93.51 – in 2018. CDKL5 only recently got one – G40.42 – which is described in this excellent article by Dr. Ana Mingorance.  Similarly, Dravet aka SCN1A just got one – G40.83 as announced here by the Dravet Foundation.  Angelman’s, CDKL5 & Dravet are some of the best organized and well-funded rare disease organizations in existence .  SRF looks at all of these as models we can emulate to better serve our community.  The fact that two of them only recently got a code shows how quickly Syngap is being recognized as a significant rare disease.

Are we getting one?

Hopefully, soon, yes.  There was a meeting at the CDC/online last week on March 18th.  A number of SRF leaders were planning on going, but the Coronvavirus turned it into an online meeting and also prevented us from sharing this article sooner.  The full agenda and proposals are available at the CDC ICD page, but the bit that really matters is repeated at the bottom of this article.  Getting on this agenda and having a speaker present on behalf of our gene is the hardest part and this milestone was hit.  So now there is a comment period and then the committee at CDC will meet and we can expect a decision in approximately six months.

How did that happen?

Hans Schlecht, MD, MMSc, a Syngap parent and Medical Lead for SRF has been in conversation with the CDC for months.  His determined and ongoing advocacy for Syngap is remarkable.  He sent an early proposal and then after further discussion with CDC he submitted another, the text of which is at the end of this article.  A careful read of Hans’ proposal and that of the FDA will confirm that they went with one of his options, an F78 code.

In parallel, another US group had requested an ICD code and the CDC asked that both groups agree on one speaker to advocate for SynGAP.  Dr. Connie Smith-Hicks from Kennedy Krieger at Johns Hopkins kindly agreed to speak for SynGAP.  

What can we do now? What do we do when we get one?

Right now, a period for public comments is open until May 18th. please send a letter to  describing your support for a SYNGAP1 code to nchsicd10CM@cdc.gov If the CDC committee grants us a code it will be implemented for use October 1, 2021 so be patient but please tell your doctors that a SYNGAP1 specific code is coming and they will need to enter that code into your Syngapian’s medical record.

Text of the CDC proposal

Here is the text from the CDC proposals that is available online at the CDC ICD page where there is also a WebEx Recording (Recording password: XepnhPB5 ) the excellent 10 minutes presentation from Dr. Smith-Hicks starts at the 2:30 (2 hour and 30 minutes, it’s a 6 hour meeting).  Here are her slides:

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ICD-10 COORDINATION & MAINTENANCE COMMITTEE MEETING – MARCH 17-18, 2020

Pages 54 & 55 of https://www.cdc.gov/nchs/data/icd/March-2020-Proposals.pdf

SYNGAP1-RELATED INTELLECTUAL DISABILITY, OTHER GENETIC RELATED INTELLECTUAL DISABILITY

There are a number of specific genes which have been found to be related to intellectual disability. One of the more common such genes is SYNGAP1. There is a SYNGAP1-related intellectual disability, and this is also frequently associated with other disorders, including epilepsy and autism. Although it is considered rare, based on prevalence data, SYNGAP1-related intellectual disability is expected to affect over one million individuals worldwide. This proposal is based on two separate requests to create a code for SYNGAP1-related intellectual disability, one from the Bridge the Gap – SYNGAP1 Education and Research Foundation, and another from Hans P. Schlecht, MD, of Springfield, MA, together with the Syngap Research Fund. Also, other requests were received from Dr. Schlecht, with support from others, to create specific codes for certain other genetic related intellectual disabilities, and related genetic syndromes (those noted are not exhaustive).

The SYNGAP1 protein is an essential contributor to function of the postsynaptic density of neurons and critical to overall neurodevelopment. SYNGAP1 insufficiency is a rare, genetic autosomal dominant disorder resulting in reduced expression of SYNGAP1 with disabling resulting conditions. Pathogenic variants of SYNGAP1 are characterized by intellectual disability and developmental delay along with varying penetrance of autism, hypotonia, sleep disturbance, maladaptive behaviors, and epilepsy (Vlaskamp 2019). While a rare disease, prevalence data demonstrate that variants are common in nonsyndromic intellectual disability with >1 million individuals predicted to be affected world-wide, making pathogenic SYNGAP1 variants more prevalent than fragile X syndrome (Hamdan 2011, Krupp 2017).

Since SYNGAP1 encephalopathy has intellectual disability as a fundamental condition—in contrast to the variable penetrance of autism and epilepsy– and is also categorized as a nonsyndromic intellectual disability, it is proposed to classify SYNGAP1-related intellectual disability within F78 “Other intellectual disabilities,” but to also note that other associated issues which may be present should also be coded separately, such as autism and epilepsy.

Creation of a specific ICD-10-CM code for SYNGAP1-related intellectual disability, as well as one for other genetic related intellectual disability, would have a number of benefits, and the submitter believes this would aid: epidemiologic monitoring, assessment of disease-associated medical costs, retrospective studies comparing best practices, encouragement of pharmaceutical research, and recruitment of subjects for clinical trials and patient registries, as well as enabling improvement of assessment of resource requirements (Valdez 2016).

REFERENCES

  • —. SYNGAP1-related intellectual disability. Genetics Home Reference. National Library of Medicine, National Institutes of Health. 2016. https://ghr.nlm.nih.gov/condition/syngap1-related-intellectual-disability
  • Hamdan FF, Daoud H, Piton A, et al. De novo SYNGAP1 mutations in nonsyndromic intellectual disability and autism. Biol Psychiatry. 2011 May 1;69(9):898-901. PubMed PMID: 21237447.
  • Krupp DR, Barnard RA, Duffourd Y, et al. Exonic Mosaic Mutations Contribute Risk for Autism Spectrum Disorder. Am J Hum Genet. 2017 Sep 7;101(3):369-390. PubMed PMID: 28867142; PubMed Central PMCID: PMC5590950.
  • Valdez R, Ouyang L, Bolen J. Public Health and Rare Diseases: Oxymoron No More. Prev Chronic Dis. 2016 Jan 14;13:E05. PubMed PMID: 26766846; PubMed Central PMCID: PMC4714940.
  • Vlaskamp DRM, Shaw BJ, Burgess R, et al. SYNGAP1 encephalopathy: A distinctive generalized developmental and epileptic encephalopathy. Neurology. 2019 Jan 8; 92(2):e96-107. PubMed PMID: 30541864; PubMed Central PMCID: PMC6340340

TABULAR MODIFICATIONS

F78 Other intellectual disabilities

New Subcategory F78.A Other genetic related intellectual disabilities

New code F78.A1 SYNGAP1-related intellectual disability

Add Code also, if applicable, any associated:

Add Autistic disorder (F84.0)

Add Autism spectrum disorder (F84.0)

Add Epilepsy and recurrent seizures (G40.-)

Add Other pervasive developmental disorders (F84.8)

Add Pervasive developmental disorder, NOS (F84.9)

Here is the text of Dr. Schlecht’s proposal to CDC

SYNGAP1 Encephalopathy

A coding system for SYNGAP1 Encephalopathy is proposed by Hans P. Schlecht, MD, MMSc and the SYNGAP Research Fund.

The SYNGAP1 protein is an essential contributor to function of the postsynaptic density of neurons and critical to overall neurodevelopment. SYNGAP1 insufficiency is a rare, genetic autosomal dominant disorder resulting in reduced expression of SYNGAP1 with disabling resulting conditions. Pathogenic variants of SYNGAP1 are characterized by intellectual disability and developmental delay along with varying penetrance of autism, hypotonia, sleep disturbance, maladaptive behaviors, and epilepsy (Vlaskamp 2019). While a rare disease, prevalence data demonstrate that variants are common in nonsyndromic intellectual disability with >1 million individuals predicted to be affected world-wide, making pathogenic SYNGAP1 variants more prevalent than fragile X syndrome  (Hamdan 2011, Krupp 2017).

As it is viewed as a developmental encephalopathy, we propose to tabulate it in the G93.4 “Other and unspecified encephalopathy” section (Option 1). Alternatively, since SYNGAP1 encephalopathy has intellectual disability as a fundamental condition—in contrast to the variable penetrance of autism and epilepsy– and is also categorized as a non-syndromic intellectual disability, we offer to tabulate SYNGAP1 encephalopathy within F78 “Other intellectual disabilities” (Option 2).

Receiving a specific ICD-10 code would be a momentous step forward for the study of this rare disease as coding would aid: epidemiologic monitoring, assessment of disease-associated medical costs, retrospective studies comparing best practices, encouragement of pharmaceutical research, and recruitment of subjects for clinical trials and patient registries, and guidance of proper reimbursement (Valdez 2016). Upon reception of an ICD-10 code, the SYNGAP1 community will then submit an analogous ICD-11 code request to insure ongoing tracking of SYNGAP1 encephalopathy.

REFERENCES

  • Hamdan FF, Daoud H, Piton A, et al. De novo SYNGAP1 mutations in nonsyndromic intellectual disability and autism. Biol Psychiatry. 2011 May 1;69(9):898-901. PubMed PMID: 21237447.
  • Krupp DR, Barnard RA, Duffourd Y, et al. Exonic Mosaic Mutations Contribute Risk for Autism Spectrum Disorder. Am J Hum Genet. 2017 Sep 7;101(3):369-390. PubMed PMID: 28867142; PubMed Central PMCID: PMC5590950.
  • Valdez R, Ouyang L, Bolen J. Public Health and Rare Diseases: Oxymoron No More. Prev Chronic Dis. 2016 Jan 14;13:E05. PubMed PMID: 26766846; PubMed Central PMCID: PMC4714940.
  • Vlaskamp DRM, Shaw BJ, Burgess R, et al. SYNGAP1 encephalopathy: A distinctive generalized developmental and epileptic encephalopathy. Neurology. 2019 Jan 8; 92(2):e96-107. PubMed PMID: 30541864; PubMed Central PMCID: PMC6340340.

TABULAR MODIFICATIONS

Option #1

Diseases of the nervous system (G00-G99)

Other disorders of the nervous system (G89-G99)

G93 Other disorders of brain

G93.4 Other and unspecified encephalopathy

G93.49 Other encephalopathy

New code G93.4902 SYNGAP1 Encephalopathy

Option #2

Mental, Behavioral and Neurodevelopmental disorders (F01-F99)

Intellectual Disabilities (F70-F79)

F78 Other intellectual disabilities

New code         F78.02 Intellectual disability secondary to pathogenic SYNGAP1 variant