Brain Malformation - Mild Lissencephaly - PACHYGYRIA Archives

November 2, 2014

Brain Growth in Teens Too

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July 14, 2014

Normal - Pachygyria - LIS Brain Sketch

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February 26, 2014

Updated Pachygyria Info
This information was updated on 2/20/14

What is pachygyria?

Pachygyria is a developmental condition due to abnormal migration of nerve cells (neurons) in the developing brain and nervous system.[1] With pachygyria, there are few gyri (the ridges between the wrinkles in the brain), and they are usually broad and flat. The condition is also known as "incomplete lissencephaly."[2][3] Pachygyria may occur alone (isolated) or as part of various underlying syndromes. Symptoms vary among affected people and may include moderate to severe developmental delay, seizures, poor muscle tone and control, feeding or swallowing difficulties, and small head size (microcephaly).[1][3] In most cases it is not inherited, but various inheritance patterns have been reported.[1][4] Treatment is symptomatic and supportive.[1][2]

Continue reading "Updated Pachygyria Info" »

February 24, 2014

Updated Information on Pachygyria and Resources

Thank you for contacting GARD. We invite you to visit the following link to view updated general information about pachygyria on our web site.

We have also identified additional information resources that you might find helpful. If any of the links we have provided do not work, please copy and paste the entire address into your browser. If you have other technical difficulties with this information, please contact or 888-205-2311 for technical assistance.

What is paracentral pachygyria?

A search of the resources available to us did not identify any information about paracentral pachygyria. It could be that this terminology is no longer in use.

Continue reading "Updated Information on Pachygyria and Resources " »

April 12, 2013

Genetics/MRI Update - New Findings

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.

Continue reading "Genetics/MRI Update - New Findings" »

November 3, 2012

How do you say Pachygyria?

Pronunciation: pak′ē-jī′rē-ă

This site makes it sound like Pak e jar e a:

June 30, 2012

Revision 21 for 'Lissencephaly - pachygyria spectrum'

Lissencephaly - pachygyria spectrum

Lissencephaly (also known as agyria) is a congenital cerebral malformation and it lies along a continuum of pachygyria; as such the term lissencephaly - pachygyira spectum is often used. It a on of many disorders of cortical formation 5, which results in a smooth cortical surface lacking the normal gyral convolutions.

Lissencephaly - pachygyria can be further divided into types I (classic) and type II, which differ in clinical presentation, underlying genetic abnormalities, and both microscopic and macroscopic (including imaging) appearances 2,6.

Continue reading "Revision 21 for 'Lissencephaly - pachygyria spectrum' " »

LIS Grading picture


Lissencephaly grading scale, with accompanying MRIs. This image shows grades 1-4, out of six total grades. Not shown, Grade 5 is mixed pachygyria and subcortical band heterotopia (SBH). Grade 6 is SBH only.

In 2006 Corey was diagnosed as mild (grade 4) posterior LIS or "paracentral pachygyria".


Normal Brain Axial View for Comparison


Corey's MRI

These are 2 views out of 1000 on the MRI CD. They may not be exact to the same view cuttings as above but close.



Continue reading "LIS Grading picture" »

May 14, 2012

2012 - 13yr with mild pachygyria in hippotherapy video

Quote from the news story by Fox16.

"It's just really fun to watch her enjoy therapy because we've done so many years of therapy where we've pushed and pushed and lots of tears," said Wendie Reaves.

Her 13-year-old daughter, Regan, is diagnosed with Pachygyria, a rare developmental disorder in the brain.

"They told us at that point that by the looks of the MRI films that she'd never walk and shed never be able to talk," said Reaves. "At this point doctors pretty just scratch their heads and say, 'She has Pachygyria? Well she's doing awesome!'"

This story is inspirational and it is here to give you all hope. Keep up the great work with your kids giving them all kinds of therapies and lots of love. You too can be amazed what your special child will accomplish in their own time.

March 22, 2012

2012 Update to Classification of Cortical Malformations

A developmental and genetic classification for malformations of cortical development:
update 2012
A. James Barkovich,1 Renzo Guerrini,2,3 Ruben I. Kuzniecky,4 Graeme D. Jackson5,6 and William B. Dobyns7,8

Recent advances in the genetics of cortical development
Brain 2012: Page 3 of 22
Progress has been made in understanding neuronal migration....

Continue reading "2012 Update to Classification of Cortical Malformations" »

January 24, 2012

Will my next child have Pachygyria?

This has been a big question asked many times on this site and rightfully so.

We all want our children to be healthy and have the best outcome in life. Yet we would never not want our child who has Pachygyria. We love them dearly. Do we have another child or play it safe without? How will we know?

The best way to find out is to have genetics done on your child. Talk with the genetic specialist who will be able to look at your history and the genetic test outcome.

I was already pregnant with Ashley when we found out Corey had Cerebral Palsy. It wasn't till years later the final diagnosis was given or put into the words of Pachygyria. Ashley is a typical, healthy child.

We did do genetics on Corey to find out the likelihood Ashley would carry it on to her future children and I was interested in the research programs. Emory Genetics did the first test which was negative. Univ. of Chicago did the second test which was also negative. Dr. Dobyns research did several other tests which also came out negative. I think that was a good sign for Ashley being typical. It is likely that her children will also be typical. The doctors did not have information on what would happen if Corey had children.

Later we found it was reassuring to family members who were contemplating getting pregnant and wanted to know if they could also have a child with Pachygyria.

On the other side, there are families that do have multiple children with Pachygyria. From my conversations with the research doctors, it seems the families with multiple cases have genetic markers found in the first test or two. India families that are intermarried have many children with Pachygyria and large families, sometimes 6 children with Pachygyria in one family. That is mainly where the researchers go for candidates to test. I have heard of a family in the US with multiple members having Pachygyria but I do not know if it was a mild case or the genetic results.

From the current families with mild cases on this site, they all have typical children beforehand and/or after.

It would be interesting and helpful for other families to add their point of view and information they have gathered on this subject. Thank you!

PS. If you do go through genetic testing, consider signing up for one or more of the Pachygyria research programs. It would be wonderful to have a cure or more readily available information on Pachygyria. Check into the research requirements first prior to doing the genetic testing. They may offer it for free or need a sample of the blood along with the results from the lab.

March 2, 2011

What is Pachygyria & Treatment

This article was found with Google Alerts using "Pachygyria" as my key word. It isn't written by a doctor but is a good general idea of what pachygyria is about and some of the treatments. It is not all inclusive as there are other issues depending on where the brain is affected. Some children also have sight and hearing issues.

( submitted 2011-01-25 by Kirthy Shetty, Ezine Articles Expert Author)

Pachygyria is a kind of pre-natal developmental disorder which affects a child and his spontaneous mental growth process. Predominantly, the condition is recognized in a child by the bulky convolutions of the cerebral cortex.

This discrepancy gets originated probably due to unusual and abnormal neuron migration in brain and nervous system development process. In case of pachygyria, the concerned gyri are found flat and broad in nature. However, the problem of pachygyria hardly affects complete brain and therefore, the symptoms often are found variable in nature. As the condition often affect partial functionality of mental development process as well as brain development process, it is called incomplete lissencephaly.

There are three common symptoms of pachygyria and these three common symptoms are delay in usual development, mental problems, and seizures. Apart from these three common issues some other associated problems are observed here like small head size, serious feeding issues, and inadequate muscle control of the baby. However almost all cases related to pachygyria is isolated in its own way and therefore the symptoms often vary from one child to another affected child.

Continue reading "What is Pachygyria & Treatment " »

December 14, 2009

Corey's 4th Genetic Test by Dr. Dobyns Research

Dr. Dobyn's research lab tested the TUBA1A gene (previous name TUBA3) with normal results. He also came across a couple “cousin” genes that he will try to get tested in another round. This is a genetic test for Lissencephaly and pachygyria.

December 12, 2009

Dr. Dobyns LIS Facts

Dr. Dobyns at the University of Chicago Medical Center is a recognized expert on birth defects of the brain, especially lissencephaly, or smooth brain disorder. Together with David Ledbetter, PhD, former director of the University of Chicago Center for Medical Genetics, Dr. Dobyns discovered the gene that causes lissencephaly in Miller-Dieker Syndrome and in other cases of isolated lissencephaly. Over the years, he has made significant contributions to the understanding and classification of many different brain malformations. To learn more about him go to

On December 7, 2009, Dr. Dobyns emailed me back with this current information.

For the classic, severe form of LIS, by age 10y about half are deceased and probably 10-20% live to age 20 years. The first 10 years are variable, sometimes hard and sometimes not. The 2nd decade gets much harder, and probably the next decade would be harder still but very few are still living. The oldest known patient with the severe classic form of LIS lived to about age 28-29 years. Children and adults with mild forms of lissencephaly may live much longer, and may even have a normal lifespan. In general, the less severe the developmental handicap and epilepsy, the longer the affected person is likely to live.

Ketogenic diet works depending on the individual child and their types of seizures.

Hyperbaric oxygen chamber therapy does not work for Lissencephaly - Pachygyria. Dr. Dobyns said hyperbaric is more effective for treating newly injured or dying tissue/nerves, and won't regenerate what is not there.

Finally, the GRADE of LIS and the TYPE of LIS are different. I used to classify LIS as “type 1” (isolated LIS, Miller-Dieker syndrome and related) or “type 2” (Walker-Warburg syndrome and related). Then other docs began writing about a “type 3” and then “type 4”. But the conditions they labeled as type 3 and 4 were basically not LIS at all. So I stopped using type 1 and 2 and use descriptors instead: type 1 is now “classic” LIS, and type 2 is “cobblestone” malformation or LIS.

I still use numbers for the severity or GRADE of LIS, at least for for kids with classic type of LIS. In this system, type 1 is the most severe, type 2 almost the same as type 1, and types 3 and 4 less severe. Types 5-6 are confusing, and refer to LIS with so-called band heterotopia.

Great Suggestion:

It is not unusual for parents to get most of the information exactly right, then mix up one or two phrases that end up making a huge difference. This is why Dr. Dobyns routinely allow parents to run tape recorders in clinic if they want.

November 21, 2009

Corey's MRI Findings by Dr. Dobyns and Dr. Walsh

Corey's MRI was originally read as Perisylvian Syndrome. However, I heard Dr. Dobyns and Dr. Walsh evaluated MRIs for free and knew we needed another opinion. Corey had received quite a few diagnoses by this time. If you are needing the results quickly you can pay for a full report.

I suggest to everyone who contacts me through this site to get a second opinion with the Dr. Dobyns and Dr. Walsh.

One, you need to know what your child really has as a diagnosis.

Two, these doctors are world experts on Pachygyria and Lissencephaly. It is very useful for them to know how many children have Pachygyria and Lissencephaly as it is so rare.

Three, it is possible your child can be in the studies and have further testing through one blood draw. We had 2 genetic tests done through our insurance and Katie Becket medicaid. The other 2 tests were done for free in the research studies. The other tests used blood drawn on the first genetic tests.


Email clippings from Dr. Dobyns at University of Chicago for Corey in 2006-2007

The correct diagnosis is "paracentral pachygyria", a mild form of Lissencephaly.

The term Perisylvan Syndrome refers to a similar malformation known as Polymicrogyria. So this is very similar, but not quite the same thing.

Hypotonic Cerebral Palsy is a non-specific label that could be used as a secondary diagnosis.

Continue reading "Corey's MRI Findings by Dr. Dobyns and Dr. Walsh" »

Lissencephaly Classifications

Lissencephaly comprises a group of malformations caused by altered neuronal migration. It pathologically involves agyria (total loss of gyri) and pachygyria (fewer, broadened gyri).

Lissencephaly is radiologically classified into six grades, depending on the relative amounts of agyria and pachygyria, and the presence or absence of heterotopy [6].

The most frequently used and revised classification of lissencephaly includes classical lissencephaly formerly called type I and cobblestone lissencephaly formerly called type II [6, 7 and 8].

Classical lissencephaly is characterized by the presence of agyria and represents as Miller–Dieker and Norman–Roberts syndromes. Agyric regions of the cerebral cortex pathologically reveal a loosely organized four-layer cortex compared to normal six layers. It usually represents as absent or hypoplastic corpus callosum, decreased size of cerebellar hemispheres and specific craniofacial anomalies.

Cobblestone lissencephaly includes a group of syndromes, Fukuyama congenital muscular dystrophy, Walker Warburg syndrome and muscle-eye-brain disease. It is characterized by an almost complete absence of cortical layer formation and associated with hydrocephalus, brain stem and cerebellum hypoplasia, congenital eye malformations and muscular dystrophy.

The term of formerly classified type IV lissencephaly is revised (Corey was given grade 4) and divided into microlissencephaly and LCH [7, 8 and 9].

LCH involves a heterogeneous group of cortical malformations without severe congenital microcephaly (>−3 SD), but some overlap between these two groups is also expected [1]. The major cause of this heterogeneity is different gene mutations, which are responsible for gross brain malformation involving both cerebral and cerebellar cortices [8, 9 and 10]. LCH was classified into six subgroups due to phenotypic and genetic properties [1, 9 and 11]. Although existence of some distinctive phenotypic features of these subgroups, there is also some overlap between them.

Continue reading "Lissencephaly Classifications" »

MRI change possible with Lissencephaly - Pachygyria

MR imaging of a patient with epilepsy and psychomotor retardation at 5 months revealed parieto-occipital pachygyria with almost normal cortical appearance and thickness in the frontal region; this appearance evolved into diffuse pachygyria at 7 years.

The change of the MR imaging findings may have resulted from myelination in the intracortical and subcortical fibers. It is important for clinicians to be aware of the longitudinal changes of the cerebral cortex in lissencephaly.

Continue reading "MRI change possible with Lissencephaly - Pachygyria" »

Ocular findings in lissencephaly

Ocular findings in lissencephaly

Journal of American Association for Pediatric Ophthalmology and Strabismus, Volume 7, Issue 3, June 2003, Pages 178-184
Naeem U. Nabi, Eedy Mezer, Susan I. Blaser, Alex A. Levin, J. Raymond Buncic

Abstract Purpose

To report our retrospective study of 20 cases with lissencephaly and describe ocular and visual abnormalities associated with this disorder.


Patients with lissencephaly were identified and classified into classic (type I) or cobblestone (type 2) lissencephaly on the basis of a review of clinical records and neuroimaging studies. Only patients examined by an ophthalmologist were included in the study.


Only 1 patient had a normal ocular examination. Ocular abnormalities included optic nerve hypoplasia and atrophy, retinal dysplasia, retinal nonattachment, macular hypoplasia, anterior segment malformation, and strabismus.


Ocular abnormalities in classic (type 1) lissencephaly are less severe. Central, steady, and maintained fixation may be present despite the presence of optic nerve hypoplasia, optic atrophy, macular hypoplasia, strabismus, or refractive errors.

Retinal and anterior segment abnormalities were observed only in cobblestone (type 2) lissencephaly. These patients often have severe visual impairment because of retinal or cortical disease.

Continue reading "Ocular findings in lissencephaly" »

The MR evaluation of pachygyria and associated syndromes.

Eur J Radiol. 1991 Jan-Feb;12(1):53-9.
The MR evaluation of pachygyria and associated syndromes
Byrd SE, Osborn RE, Radkowski MA.

Department of Radiology, Children's Memorial Hospital, Northwestern University Medical School, Chicago, IL.

A retrospective study of 40 children with some form of pachygyria was performed at the Children's Memorial Hospital in Chicago. All 40 children had MR brain scans. We analyzed the MR findings, and correlated these findings with the clinical symptoms and course in all the children. We have autopsy findings in 15% these children. Based on our clinical, MR and autopsy findings, in conjunction with the medical literature, we found the following:

(1) Pachygyria can occur as an isolated entity without an association with lissencephaly. The MR findings in these children consisted of a brain that demonstrated normal opercularization with either focal or diffuse areas of pachygyria without areas of agyria. These children live longer and have less severity of symptoms than the children with lissencephaly.

(2) The MR findings in children with lissencephaly consisted of a brain that demonstrated abnormal opercularization with areas of total agyria or areas of agyria with pachygyria.

(3) The MR findings in 25% of our children with polymicrogyria simulated pachygyria. The MR findings of the brain in these children consisted of a 'nubby' appearance to the outer surface of these abnormal gyri which resembled pachygyria but on histologic exam was polymicrogyria.

PMID: 1999213 [PubMed - indexed for MEDLINE]

Continue reading "The MR evaluation of pachygyria and associated syndromes." »

October 11, 2009

Missing protein in rare genetic brain disorder restored

The Times of India ANI7 September 2009, 04:51pm IST

By using protease inhibitors, researchers at the University of California-San Francisco (UCSF) have restored to normal levels a key protein that

Missing protein in rare genetic brain disorder restored (Getty Images) is involved in early brain development, and causes the rare brain disorder lissencephaly.

Reduced levels of the protein called LIS1 have been shown to cause lissencephaly, which is characterized by brain malformations, seizures, severe mental retardation and very early death in human infants.

The findings in mice offer a proof-of-principle that the genetic equivalent to human lissencephaly, also known as "smooth brain" disease, can be treated during pregnancy and effectively reversed to produce more normal offspring.

The researchers are hoping that this approach could also be used to treat other defects in utero, or even those manifesting after birth, when caused by a partial deficiency in one gene, according to Dr. Anthony Wynshaw-Boris.

"Researchers have not considered it possible to treat such a pervasive, early developmental brain disorder as lissencephaly. Not only were we able to show a clear cellular effect from using these protease inhibitors, but also were able to treat the disorder in utero," Nature quoted Wynshaw-Boris as saying.

The work is the culmination of 15 years of collaborative research into the cause and mechanisms of lissencephaly, which is caused by a deletion or loss of one copy of the LIS1 gene, and affects an estimated one in 50,000-100,000 infants.
In 1998, the researchers reported of producing a mouse with the same mutation that displayed defective brain development.

The current research used these mice, and found that the protein calpain degrades the LIS1 protein to less than half its normal levels near the surface of the cells. The team then used a specific small-molecule protease inhibitor of calpain in these mice.

At a cellular level, the protease inhibitors enabled LIS1 protein to be expressed at near-normal levels. The team then gave daily injections of a calpain inhibitor to pregnant mice whose foetuses had the mouse-model of this defect. They observed that the resulting offspring had more normal brains and showed no sign of mental retardation.

"This study is really a proof-of-principle not only for treating complex developmental brain disorders, but also for any disorder with reduced protein levels where proteases normally play some role in breaking down that protein. This will be much more difficult to apply to humans, because of the safety issues involved, but it could lead to new therapies that might be effective for a wide range of developmental disorders," said the researchers.
The findings have been published in the journal "Nature Medicine".

March 18, 2009

Lissencephaly - Pachygyria Brain information

The variant of lissencephaly or pachygyria that Corey has is mild and does not relate to most of the lissencephaly information listed on the internet and that is why we have this website to let other parents in our situation know:

The mild variety of pachygyria has a full life expectancy.

The lissencephaly sites we found state the life expectancy is up to 20 years of age.

I ran across this site with an actual picture of a pachygyria brain. It states it is fatal but I was told Corey's variant is not. A total of 13 brain malformations are included.

For description and resources:

Brain scans of Lissencephaly and information visit:
Lissencephaly is the most severe of the migrational anomalies. Affected individuals are profoundly mentally retarded and usually have severe seizure disorders. A global migrational abnormality is postulated, occurring between 11-26 weeks. The cortex is abnormally thickened and sulcation largely absent, with 2-4 instead of the normal 6 cell layers of cortex. Colpocephaly is usually present.
I-Miller-Deiker- assd with 17p-

Genetic Testing for Pachygyria - Lissencephaly

What is Genetic Testing?

A genetic test is the analysis of human DNA, RNA, chromosomes, proteins, or certain metabolites in order to detect alterations related to a heritable disorder. This can be accomplished by directly examining the DNA or RNA that makes up a gene (direct testing), looking at markers co-inherited with a disease-causing gene (linkage testing), assaying certain metabolites (biochemical testing), or examining the chromosomes (cytogenetic testing). Selected methodology terms are used in the GeneTests Laboratory Directory.

Genetic Tests for PACHYGYIA or Lissencephaly 1 (LIS1)

These tests were completed on Corey through Emory and Univ. of Chicago.

TEST 1: Lissencephaly Type 1: Miller-Dieker is the first Chromosome 17 testing done on Corey at Emory University. This test came back normal for Corey. 2006 (If normal do test 2)

TEST 2: Sequencing of the LIS1 gene can only be done at the University of Chicago or at two labs in Germany. This test came back normal for Corey. 2007 (If normal do test 3)

TEST 3: MLPA-based dup/del test - The yield is high, at least 1/3 chance of finding an abnormality. This test came back normal for Corey. 2007 (He is now a candidate for the research program with Dr. Dobyns.)

All the testing required just one blood draw at Emory in Atlanta. It was about 4-5 vials of blood but went quickly. Emory was very helpful working with Univ. of Chicago and the billing. The in state work on test 1 was covered by insurance and medicaid. The other 2 tests out of state are billed to my insurance and the remainder paid by us.


Chromosome 17 has the "address" to LIS 1. To learn more about chromosomes and genetic testing visit

Syndromes with lissencephaly. I:
Miller-Dieker and Norman-Roberts syndromes and isolated lissencephaly.


Although genetic testing shares some features in common with other kinds of laboratory testing, in many ways it is unique and requires special considerations.

Continue reading "Genetic Testing for Pachygyria - Lissencephaly" »

September 25, 2006

Dr. William Dobyns - Human Genetics

Since this posting was created Dr. Dobyns has moved to Seattle to continue research.

New address:

Please send all samples and records to:

Seattle Children's Research Institute
1900 Ninth Avenue, 10th Floor
Seattle, WA 98101

To schedule a clinic appointment with Dr. Dobyns:

Family Service Coordinators for Genetics

William B. Dobyns, M.D.
Seattle Children's Research Institute
Center for Integrative Brain Research
1900 Ninth Avenue
M/S C9S-10, Room 1020
Seattle, WA 98101
Office: 206-884-1025
Fax: 206-884-1210



See this site also for a listing of his publications and research funding.

Board Certification(s): Medical Biochemical Genetics and Psychiatry
Mayo Medical School, Rochester
Residency: Gundersen Medical Foundation - La Crosse Lutheran, La Crosse, Pediatrics
Fellowship: Baylor College of Medicine, Houston, Neurology
Mayo Graduate School of Medicine - Mayo Foundation, Rochester, Medical Biochemical Genetics

Research Description
William Dobyns, MD, has made major contributions to the field of human genetics, particularly the nature and genetic causes of developmental disorders including mental retardation, autism and brain malformations.

As both a medical geneticist and pediatric neurologist, Dr. Dobyns offers a rare combination of expertise. He examines patients with all types of genetic diseases, emphasizing children with complex developmental problems. He also offers genetic counseling for families of these children.

Dr. Dobyns is a recognized expert on many complex developmental disorders of the brain including mental retardation, autism, birth defects of the cerebellum such as Dandy-Walker malformation, and birth defects of the cerebral hemispheres such as microcephaly and megalencephaly (small and large brain size), lissencephaly or "smooth brain" disorder - (also pachygyria), and polymicrogyria (pebbled brain surface).

He has made significant contributions to the understanding, classification and genetic cause of many different developmental disorders.

Research Focus Area
Genetics and Developmental Biology, Developmental Cognitive Neuroscience, Neuroscience / Neurodevelopment

Continue reading "Dr. William Dobyns - Human Genetics " »

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