Center for Brain Development


Undiagnosed Neurogenetic Disease Center

Mission

Rare and yet to be described diseases present many challenges to patients, families, and physicians. Some children seen at Rady Children's Hospital, San Diego, and elsewhere wait years for a diagnosis due to medical complexity or symptoms that cannot be explained by standard medical knowledge.  In some cases, a diagnosis never comes.  Frequently these children have undergone expensive, and often, painful diagnostic procedures, and families are still left without an answer, and therefore lack definitive treatment or an understanding of their disease. The Undiagnosed Neurogenetic Disease Center aims to use cutting edge technologies and a focus on undiagnosed diseases to identify rare and yet to be described disorders.

Summary

The advent of genome sequencing now makes it possible to evaluate Rady Children's Hospital patients for nearly all known neurogenetic conditions with a single genomic sequencing test. Genomic medicine has the potential to change lives through improved diagnosis and care. Nowhere is this more apparent than in conditions affecting the children involving disorders of nervous system function, collectively termed "neurodevelopmental disorders". We aim to identify and recruit patients that have already undergone an extensive medical and/or genetic evaluation yet the diagnosis, and therefore definitive therapy, remain elusive.

Although this is a research study currently, we expect that this technology will be introduced into routine medical care in the near future. Thus we wish to open access to patients referred by their primary doctor or specialist with an undiagnosed disease for medical DNA sequencing.

Brief Overview of Services

Of the total number of cases that are referred to this program, a very limited number will be invited to proceed in the study following careful application review by the program’s medical team. In general, it takes 8-12 weeks for the UNDC staff to evaluate an application, and then 4-6 months for genetic evaluation. Families will need to agree to the terms of the study, and provide a saliva sample from the child as well as siblings and parents. Our goal is to enroll 50-100 patients over the next year.

Team

Dr. Joseph G. Gleeson, Professor, Neuroscience and Pediatrics, Senior Staff, Neurology, Rady Children's Hospital

Dr. Bruce Barshop, Professor, Pediatrics and Genetics, Senior Staff, Biochemical Genetics, Rady Children's Hospital

Dr. Keith Vaux, Professor, Pediatrics and Hospital Medicine, Dysmorphology and Teratology, Rady Children's Hospital

Services

Families agreeing to the terms of the study will provide a saliva sample from the child as well as siblings and parents. Our goal is to enroll 50-100 patients over the next year. If you are a medical doctor treating a child where the genetic cause is uncertain, or if you are a parent caring for a child with a likely neurogenetic condition where the medical system provides no answers, please consider contacting us for more information.

For Parents

Following careful application review by the program’s medical team, a very limited number will be invited to proceed in the study. The referral is best coordinated through your child’s doctor but we also will consider applications from parents or family members. In general, it takes 8-12 weeks for the UNDC staff to evaluate an application, and then 4-6 months for genetic evaluation. Families will need to agree to the terms of the study, and provide a saliva sample from the child as well as siblings and parents. Our goal is to enroll 100 patients over the next year.

For Professionals

Genomic medicine has the potential to change lives through improved diagnosis and care. Nowhere is this more apparent than in conditions affecting the children involving disorders of nervous system function, collectively termed "neurodevelopmental disorders". We aim to identify and recruit patients that have already undergone an extensive medical and/or genetic evaluation yet the diagnosis and therefore definitive therapy remain elusive.

In some cases it will be impossible to differentiate between environmental causes such as prematurity, previous infections, toxins, and underlying genetic mechanisms. However, for our study, we seek to limit our recruitment to patients with likely genetic causes of disease, and have put in place an expert team of specialists to pour over each case individually to determine the likelihood of benefit from our program. This evaluation will include a detailed review of medical records, physical examination, and in some instances suggestions to the referring physician of additional standard medical testing.

Once the patient passes through this initial phase and is invited to participate in the genetic phase of the study, the family will agree to participate through a standard ethically-approved consenting process, then saliva or blood samples will be obtained to extract DNA. The DNA samples will undergo detailed genome-wide sequencing, either "whole exome" or "whole genome" sequencing. The results will be analyzed with cutting edge research technology and compared with all of the available genome sequencing worldwide in order to identify a likely genetic cause. Referring physicians will be notified of any pertinent genetic findings, and will seek to have any relevant results validated in a clinically-certified (CLIA certified) laboratory.

Contact

Referring physicians and parents can contact <gleesonlab@ucsd.edu> or call 858-822-3786 for patient referral. Please indicate if the family has agreed to be contacted for participation in this study.