Test 1: 12/22/06 testing for deletions of chromosome17 by FISH analysis was completed and normal. See Genetic Testing report by Emory University, Dr. Daniel Gruskin, MD.
Test 2: 5/07 LIS1 sequencing = normal. See report completed by University of Chicago.
( Corey has real LIS with a LIS1 pattern, although less severe than typical. Since LIS1 sequencing was normal, suggest MLPA-based dup/del testing. The yield is high, at least 1/3 chance of finding an abnormality.)
Test 3: 7/2007 MLPA-based dup/del testing = normal. Dr. Dobyns research. Do not have report.
Test 4: 2008 TUBA3 – Dr. Dobyns research – Normal – do not have report. Dr. Dobyns research lab tested the TUBA1A gene (previous name TUBA3) with normal results. He has come across a couple “cousin” genes that he will try to get tested in another round.
Summer of 2012 Update:
1) When doing an MRI ask for the 3T scanner. This is not at all hospitals and they are quite expensive. However, they can give more details than the 1.5T scanner and can tell better the extent and degree of pachygyria. (We were not able to get a 3T at this time.)
2) Dr. Dobyns has been working with new forms of Lissencephaly.
Corey’s brain scan pattern resembles the form of LIS seen with mutations of another new gene: DYNC1H1. This gene also may cause problems with peripheral nerves.
Mike and I sent in our DNA for research. Corey is one of 3 Dr. Dobyns has ever seen with this type of brain image and it matches DYNC1H1 gene. If it is Corey has a chance of losing his feeling in his hands and feet due to peripheral nerve damage. I asked if it would come and go and he said no it is a gradual loss and permanent. Corey had a nerve conduction velocity study done. He didn’t need the 2nd part with the needle but needed the nerve impulse part of the test. Corey’s test was normal and we have a good baseline. Corey is most affected in the perisylvian region under his ear area.
3) Walsh Lab wrote to me with a possible DCX gene to consider.
DYNC1H1 gene mutations are an established cause of some types of muscle disorders but has recently also been shown to be associated with cases of brain malformations, that would be why it was not thought of until this year. It looks like a lab in Germany is the only lab offering clinical testing for DYNC1H1 and it is very expensive, so perhaps starting with DCX, which is available at a number of labs in the US, might be the first place to start.
7/3/2014 – DYNC1H1 is normal. Corey was included in the NCHIP study. His scans very clearly show posterior predominant mild-mod LIS.
5/22/2015 SCN9A gene – Dr. Dobyn, Dr. Mirzaa research team came up with SCN9A gene – Febrile seizures and congenital inability to experience pain – mild. This was found in a study for mental delays, autism and seizures. Calcium channel gene. This gene happens when both mom and dad carry the variant and the child gets 2 defective/variant copies. It is more common for European descent to have one copy of the variant gene and no problems – 1 out of 1000 people. Having 2 defective /variant copies is rare. This SCN9A gene however may give some answers to the type of seizure med to use with the febrile seizure component. This component also may be the reason his seizures are more resistant to treatment and I’m wondering if it also has to do with him having seizures when he gets hot. Mike and I both had a close relative with febrile seizures, one being my dad. We will have another conference call in a month with results they will find from networking with genetic epidemiologist around the world studying this gene, most prominent in England. Corey is being added to another LIS research project as the LIS gene has not been found yet for him.
The congenital inability to experience pain is luckily mild but we have experienced it with Corey and it is a safety concern. He does not feel intense “internal” pain immediately and can take a day to react to an injury or sickness. He sprained his ankle and ran on it for an hour without knowing and never said anything to the teacher or me. I found it swollen like a baseball about 5 hours later, still no reaction to pain till the next day. Third degree burn on hand after he put his hand on a light bulb at school. No reaction and I found it at dinner time with his palm of his hand swollen and blistered badly the size of a 60watt light bulb. He was not able to tell us what happened till next afternoon with speech help and teacher being a sleuth. Pain only when changing dressing – surface. He had an emergency appendectomy at 12 which was about to rupture with only minor stomachache and he was pale. He fell on his face when he was young and permanently dented his cheek without much fuss. He fell down the stairs, another fall, etc. Corey does feel surface pain more intensely such as a scratch. Written by Candice Lange from phone conversation. Since this was done in a research setting we will need to go to a local geneticist for the gene to be run and a professional report written. William B. Dobyns, MD, Professor of Pediatrics and Neurology University of Washington, and Principal Investigator Center for Integrative Brain Research, Seattle Children’s Research Institute 1900 Ninth Avenue, M/S C9S-10, Seattle WA 98101, firstname.lastname@example.org
7/31/15 – GENE TUBG1 Lissencephaly mutation mild… Not carried by parents. Developmental handicap and epilepsy. Need confirmation by clinical lab. 1 of 5 kids. 3 published. One little girl took 22 yrs to find. Corey took 9 (2006 entered research). This gene was IDd 2 years ago 2013.
Hot water exposure is a minor trigger for seizures generally. It is a major trigger for seizures in children with mutations of a gene known as SCN1A (a.k.a. Dravet syndrome). One paper suggests that Corey’s gene – SCN9A – may also be a cause for a variant of Dravet syndrome.
2017 – Corey remains in Dr. Dobyns research program. We are truly grateful for his team and his dedication to pachygyria.