Facts about L1CAM Syndrome

What is L1CAM Syndrome?


L1 CAM [Cell Adhesion Molecule] Syndrome: everyone has the L1CAM Gene which in turn creates the L1 Protein; the problem arises when amino acids fail to allow the gene to form correctly (1). L1 Syndrome accounts for approximately 2-15% of newborn males born with hydrocephalus(9), and according to the Genetic Home Reference HSAS seems to occur between 1/25,000 to 1/60,000 births. The prevalence of all L1 Syndrome cases is not known (10). Prenatal death is not uncommon (11).

The reason the L1 Gene is so critical in forming correctly is because it forms the L1 protein which is all over our entire nervous system. Our nervous systems have what are called myelin sheaths, synapses, and neurons. The L1 Protein affects these pieces of anatomy’s formation. The protein allows our body to send chemical signals. (1) When our protein cannot form correctly because the gene was created incorrectly, our nervous system cannot function properly. The L1 gene contains 1,256 amino acids… should any one of those amino acids be sequenced incorrectly, the nervous system cannot function properly. Thus, an L1 Syndrome affected boy is affected by so much more than just hydrocephalus. In summary: L1 Gene forms wrong. L1 Protein forms wrong. Nervous system cannot function correctly. Hydrocephalus develops. Hydrocephalus is truly a symptom of our boys’ overall condition.

Because the condition is passed through the x-chromosome, boys with one affected chromosome are affected while females with one affected chromosome are carriers. There are no known males, as of 2004, who have reproduced (5). Generally, mutations are unique to each family line, with very little cross-over, and each affected boy within a family is affected uniquely (2).  Most commonly seen symptoms include hydrocephalus, both low and high muscle tones, adducted thumbs, and mental and physical delays. Some boys lack attributes such as adducted thumbs and hydrocephalus severe enough for shunts, while other boys are non-verbal and wheelchair bound. Most adducted thumb boys are shunted, not all are (3).


Fun Fact of the Day ** the human L1 sequencing is 92% similar to that of a mouse! (4)



How Does X-linked Hydrocephalus Affect Our Boys?

When I explained L1 Syndrome the night before I delivered, I had no idea what to expect for my son. I didn’t really care about the science of L1 at the time (anything listed above). I cared about what my husband and I could do now, how it would affect our son, and how this genetic condition would change our family. All of my research left me with a bunch of new big long words. However, a few weeks prior to delivery,  I found an amazing support group of L1 Syndrome parents online. If you are reading this as a parent with an L1 child, please contact me and I can give you information to join this support team!

In the mean time, I hope this information can help you as well as people who care about L1CAM and our families begin, or add to, your own research into the L1 Syndrome world. Prenatally there is nothing you can do except monitor closely and deliver (possibly) early. You should come to terms with the fact that a surviving L1 Child will make a huge change in your life; you will become a medical expert and your entire life will revolve around appointments and therapies. You will learn to trust your doctors while questioning their every decision. Your life will be amazing.


The Real Deal: Details

The term Hydrocephalus means that there is extra cerebral spinal fluid on the brain that can not be absorbed like normal. Some of our L1 boys have enlarged ventricles (a part of the brain), but no shunt. Others have shunts. HSAS, hydrocephalus with stenosis of aqueduct of Sylvius, is the most common form of hydrocephalus for our boys (5); although, not all L1 boys’ aqueduct of Sylvius is affected. Most of the boys affected by HSAS will also exhibit adducted thumbs (8), but not all, and spasticity (5). Some will learn a shuffling gait. Others may be wheelchair bound.


Each L1 patient is different, and each family owns its own individual mutation, but typically the disruption caused by the mutation is a huge one that the body cannot completely compensate for. Each child will have their own individual strengths and weaknesses. Each will need their own therapists and specialists. Your child will have good days. He will have bad days. There is no way to predict what our boys will be able to accomplish, they are each one of a kind. (3) The severity of hydrocephalus, head circumference, and shunting is independent of intellectual ability (6). This is because increased ventricular pressure alone is not responsible for mental ability alone. Unlike a typical hydrocephalus patient, L1 boys have a genetic cause. As described above, the protein the gene creates affects the whole nervous system, not just the physical pressure of fluid (11). Studies are also clear that the location and type of mutation on the gene directly correlates to severity (7).

Some L1 Syndrome boys are diagnosed with MASA (now considered umbrella’ed by L1CAM diagnosis): mental delay, aphasia (delayed speech), spastic paraplegia [shuffling gait], and thumbs. Others are diagnosed with CRASH. Oftentimes, there is increased pressure in the third ventricle that varies patient to patient, and less severe physical and mental delays (5). Both of those diagnoses names are no longer used and considered L1CAM Syndrome of varying severity.


As of 2004, there were 15 reported cases of Hirschsprung disease in correlation with HSAS; however, it is not believed that a single mutation alone on the L1 Gene causes Hirshsprung disease (5). Additionally, Agenesis of the Corpus Collosum (ACC) affects some of our boys: complete or partial, hypoplasia, displasia, or aplasia (5). These boys also exhibit spasticity.


40% of males affected by L1 Syndrome are known as a de novo L1 variant (5), or a simple case, in which mom is not a carrier. And less than 5% of female carriers present with any clinical symptoms. Those that do are usually presented with adducted thumbs and/or sub-par mental intelligence. There was one case of severe hydrocephalus in a carrier female (6).


Just Remember

For those of you researching, it is important to remember that while some sources of information are great and reliable… they were written long ago. This 1997 article CRASH Syndrome: Mutations in L1CAM Correlate with Severity of the Disease is an excellent article packed with information. The acronym CRASH was coined in 1995, but is no longer used (10). However, there are certainly more than 70 mutations reported now in 2016. For L1 Syndrome boys who were diagnosed with MASA, this article explains how the term CRASH came about because it seemed to be more appropriate at the time. Medical scientists later realized that L1CAM Syndrome encompassed both MASA and CRASH and was more appropriate of an umbrella name, understanding that severity would vary (7). All of the once-thought-to-be separate conditions are now realized to be overlapping in the L1 CAM diagnosis (12).

What’s the Hardest Part?

The hardest part of L1 Syndrome is the waiting and the unknown. But what’s silly? I have a healthy daughter. Just like we don’t know if Noah’s shunt will ever fail and need revision (need surgery), we don’t know if Kara will ever fall and break an arm (need surgery). Its important to remember that everything in life God blesses us with is unknown. We are all waiting for the unknown. Our L1 boys are absolutely no different!

(1) Genetics Home Reference. L1CAM gene. 2016.
L1cammutationdatabase.info. l1camdatabase.info. 2016.
(3) Freshly Messy. Loveable L1 CAM Syndrome Boys & Families. 2016.
(4) Omim.org. [Giffin, McKusic] OMIM Entry – 308840 – L1 CELL ADHESION MOLECULE; L1CAM. 2016.
(5) Stumpel C, Vos Y. L1 Syndrome. University of Washington, Seattle. 2015.
(6) Stumpel C, Vos Y. L1 Syndrome. University of Washington, Seattle. 2015.
(7) Yamasaki M, Thompson P, Lemmon V. CRASH Syndrome: Mutations in L1CAM Correlate with Severity of the Disease. Neuropediatrics. 1997
(8) Goldfarb C. Congenital Hand and Arm Differences: L1 Syndrome and the Thumb. Congenitalhandwustledu. 2013.
(9) S Kenwrick D. X linked hydrocephalus and MASA syndrome. Journal of Medical Genetics. 1996;33(1):59.
(10) NORD (National Organization for Rare Disorders). L1 Syndrome – NORD (National Organization for Rare Disorders). 2016.
(11) Zumoto S, Yamasaki M, Arita N et al. A new mutation of the L1CAM gene in an X-linked hydrocephalus family. Child’s Nerv Syst. 1996.
(12) Fransen, VanCamp, Vets, Welliams. L1-associated diseases: clinical geneticists divide, molecular geneticists unite. Oxford University Press. 1997.



Photos of x-linked Hydrocephalus Babies


l1 baby corbin
l1 baby james
l1 baby jonah
l1 baby nathan
l1 baby riley
l1 baby noah
l1 baby clayton
l1 baby alfredo
l1 baby logan

l1 baby max

l1 baby noel


Noah’s Story
What is Wrong with Our Baby Boy?
Baby Boy Eagle Has A Name! He’s Born!
My Two Day Old Warrior
Totally In Love, Noah’s Improving at 5 days old
Noah’s Moving On Up
There’s Hope In Progressive
The First of the Setbacks
Back on the Road to Recovery
Slow and Steady Wins the Race
Steps Toward Home
Noah’s First Week Home
The Therapy Journey has Begun
7 Weeks Alive
Noah is Enabled; never DISabled
Noah’s Brain Development
My Little Family
L1 & The Pediatric Ophthalmologist
Really, What is L1? (this post)


  1. Pingback: A Frantic Day in the Life of: an L1 Family | Freshly Messy

  2. gigi

    Your son is beautiful and your photos are just gorgeous!

    1. freshlymessy (Post author)

      Thank you so much, Gigi! That really means a lot!

  3. Jake

    Thank you for your amazing writing talent and subject expertise.

    1. freshlymessy (Post author)

      Thank you for taking the time to learn about L1!

  4. Matthew Neal

    How can I become a part of an L1 syndrome community? My wife and I are expecting our boy in February.


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