Research

The goal of this study is to learn more about tumors that form in and around the adrenal gland (pheochromocytoma and paraganglioma). Preliminary evidence suggests that inherited forms of these diseases are associated with mutations in genes involved in the succinate dehydrogenase pathways. We aim to characterize the relationship between these mutations and the disease, with the goal of improving diagnostic, prevention, and treatment techniques.

Qualifications

1. EITHER, the patient has both of the following:
   • At least one pheochromocytoma or paraganglioma 
   • Clinical or molecular exclusion of Multiple Endocrine Neoplasia type 2 and von Hippel-Lindau syndrome 
2. OR , the patient has a known mutation or variant of uncertain significance in any of the following genes:
   • SDHB
   • SDHC
   • SDHD

If you have questions about eligibility, please email  pten@ccf.org  or fax (216.636.0009 or 216.445.6798) the patient's pedigree and a clinical summary to the GC coordinator.

Study Description

We are enrolling patients with pheochromocytoma and paraganglioma to study succinate dehydrogenase genes SDHB, SDHC, and SDHD. MEN 2A and VHL must be ruled-out through molecular testing or clinical assessment. We are also interested in enrolling patients who have a known SDHB, SDHC, or SDHD variants even if they have not developed pheochromocytoma or paraganglioma. Mutation and deletion analyses are performed on the SDHB, SDHC, and SDHD genes.

Methodology

We will extract DNA from patient blood samples to look for mutations, deletions, and/or duplications in the succinate dehydrogenase genes SDHB, SDHC, and SDHD.

Results of the Study

Clinically relevant results are provided via confidential email to the referring healthcare provider. Per our institutional IRB requirements, the exact nomenclature cannot be disclosed. However, if a deleterious mutation is identified, we can share the exact mutation nomenclature with the clinical lab of your choice for site-specific analysis. At present site-specific MLPA analysis is not clinically available, but we are happy to share abnormal MLPA results with the clinical lab of your choice as well.

How to Enroll

Healthcare provider referral only (patients may not self-enroll)

Required documents
This study requires referral and completion of study enrollment packet by patient's healthcare provider 

This downloads page has been updated with new forms which will be effective from September 23, 2022 until September 22, 2023. We will not accept any previous versions of these documents. To access the new forms, please clear your browsing history and computer cache.

For all external referrals for enrollment, please forward: Enrollment packet (linked here), pedigree, and Requested medical records available to you.

For our Spanish speaking patients:
Permission to Contact (Spanish)  (PDF)
CCF Release Form (Spanish) (PDF)

The aim of this study is to learn more about susceptibility to cancer in patients with PTEN variants. The goal is to characterize the genetic changes that may increase an individual’s chances of developing cancer. The researchers are also looking to understand the relationship between microbes, cancer and autism spectrum disorder. For more information about this research study, view a summary (PDF).

If you are a patient who is interested in asking your healthcare provider for a referral, please  review the "The PTEN Study: Information for Prospective Participants" flyer (PDF) we wrote especially for you.

Qualifications

Inclusion criteria
Patients with the following will automatically qualify for study participation: 

• Meets one of following combinations of criteria from our Clinical Features Checklist  (PDF)
  • 2 major criteria
  • 1 major criteria + 2 minor criteria
  • 3 minor criteria

• Adult patients with a score of 10 or greater per the Cleveland Clinic PTEN Risk Calculator ( Calculate Risk)
• Pediatric patients with macrocephaly plus at least one of the following :
  • Autism/mental retardation/developmental delay 
  • Lipoma, biopsy-proven trichilemmomas, oral papilloma, or hemangioma 
  • Arteriovenous malformation 
  • One or more gastrointestinal polyps 

• Known PTEN pathogenic or likely pathogenic variant, or variant of uncertain significance 
• Lhermitte-Duclos disease 
• Pigmented macules of the glans penis 
• Clinical diagnosis of Proteus or Proteus-like syndrome 

Exclusion Criteria
Patients with the following will automatically be disqualified from study participation:

• Patients without a documented OFC (head circumference) measurement 
• Patients with non-PTEN genetic testing (i.e. BRCA1/2 testing) pending. 
• Patients with qualifying features that can be explained by existing non- PTEN -related test results

Note: While we do not strictly require that other diagnoses be ruled out prior to enrolling patients in this study, we do ask that you help us use our research funding as wisely as possible. Our genetic counselor coordinator is glad to discuss the differential diagnosis or testing strategy for any patient. 

If you have questions about eligibility, please email pten@ccf.org or fax (216.636.0009) the patient's pedigree and a clinical summary to our study staff.

Study Description

This is an integrated study with DNA, RNA, and protein studies of the PTEN gene and related pathways. We are studying the frequency of characteristics such as cancer diagnoses among those with PTEN alterations; working to clarify variants of uncertain significance; and exploring alternative mechanisms of disease in patients without identified variants. This is a multi-faceted research study that combines clinical patient information. We ultimately hope that this research will lead to the development of targeted molecular therapies for persons with PTEN alterations.

Methodology

Gene sequence abnormalities for the PTEN gene (coding region, exon/intron boundaries, flanking intronic sequences) are analyzed: 

• Legacy samples (2005-2020) have all undergone mutation scanning and MLPA (large rearrangement) analysis of all nine PTEN exons.
• The majority of research participants accrued beyond 2020 have already had clinical genetic testing in CLIA certified labs.
• Research participants without genetic testing results who are interested in participating will be referred for clinical PTEN mutation and deletion/duplication testing, if warranted, after discussion of such cases during weekly family review meetings.

Results of the Study

Results will be shared with the patient in the form of publication summaries upon completion of the study. If, in the course of lab analysis, clinically relevant results become available, they will be reported to the medical provider of record.

How to Enroll

Healthcare provider referrals only (Patients may not self-enroll)

Please complete and forward the five documents in our enrollment packet, as well as all requested medical records ( see clinical features checklist).

If you have questions about eligibility, please email  pten@ccf.org  or fax (216.636.0009) the patient's pedigree and a clinical summary to our study staff.

Scheduling with the Cleveland Clinic PTEN Multidisciplinary Clinic

New or returning patients interested in scheduling with the Cleveland Clinic PTEN Multidisciplinary Clinic should contact the PTEN Navigator by phone at 216.444.4044 or by email at claytoi@ccf.org. In the event the PTEN Navigator is assisting another caller, please leave a message with your name, return phone number and reason for your call. The PTEN Navigator will get back to you within 48 hours.

New PTEN Patient Scheduling
If you are a new patient scheduling with PTEN Multidisciplinary Clinic, please contact the PTEN Navigator by phone 216.444.4044 or by email at claytoi@ccf.org. You will be asked to forward insurance information as well as pertinent medical records and then you will be scheduled for a phone intake appointment with the PTEN Research Nurse. During the intake, the nurse will ask you about your medical history, clinical genetic testing and any specialists that you may need to see. After the intake call is completed, the PTEN Navigator will begin scheduling your appointments during your identified date(s) of availability.

Established PTEN Patient Scheduling
If you are a returning patient to the PTEN Multidisciplinary clinic, the PTEN Navigator will schedule a brief check-in call with the PTEN Research Nurse, and will schedule you with Dr. Charis Eng according to available dates. During the busiest seasons for the PTEN Clinic (spring, summer and fall) we may ask that you schedule your own specialist appointments so the PTEN Navigator can fully assist brand new PTEN Clinic patients. Please call 866.320.4573 to schedule non-GMI appointments.

The purpose of this study is to learn more about the symptoms and characteristics of individuals with autism and PTEN alterations, with the goal of informing risk management guidelines. The researchers may also learn new things about the genetic, biochemical, cognitive and/or behavioral problems associated with autism and/or PTEN alterations that may help diagnosis and treatment of individuals in the future.

Qualifications

Patients qualify for this study if they

• Individuals ages 18 months old and older at the time of consent who have a confirmed PTEN mutation [required]
• Have been diagnosed with Autism Spectrum Disorder [optional]
• Primary communicative language must be English or Spanish

Study Description

The goals of the study are to better understand molecular, brain, and behavioral differences and their development, identify markers of PTEN mutations with autism that can be used in future clinical trials, and to build a biorepository to continue to study patients and move toward better treatments.

For more information about this research study, please  view a summary  (PDF).

Methodology

This study has a two-year duration and involves three onsite visits for children and two onsite visits for adults. Study assessments may include medical history/family history, physical exam, neurobehavioral/cognitive evaluations, questionnaires/interviews, blood sample(s), optional seizure tracking, and, if applicable, electroencephalogram (EEG).

Results of the Study

Results will be shared with the patient in the form of publication summaries upon completion of the study. If, in the course of lab analysis, clinically relevant results become available, they will be reported to the medical provider of record.

How to Enroll

Patient opt-in and healthcare provider referrals accepted (Patients may self-enroll)

Please contact the PTEN clinical research team at 216.445.5850 or  pten@ccf.org . You will be contacted by a member of the research staff who can explain what is involved with study participation as well as the informed consent and appointment scheduling process.

The purpose of this study is to validate a new online neurobehavioral evaluation tool (NET) with both parent/informant questionnaire scales and webcam-collected patient performance measure data that can be collected from home.

Qualifications

Participants will be recruited in pairs, according to the criteria

1. Either of the following:
• Individuals aged 3-45 with diagnosed PHTS
• OR Individuals aged 3-45 with diagnosed PHTS and diagnosed neurodevelopmental disorder(s)
2. Participant #1’s caregiver or a key informant

Study Description

We are recruiting approximately 60 individuals with PHTS, ages 3-45. The anticipated sample will include approximately 30 people with PHTS without NDD (neurodevelopmental disorder), approximately 30 people with PHTS with NDD, and possible sibling controls. Along with participants, we will recruit their caregiver or a key informant. Data from the final survey and performance measures will be collected online from each participant pair at baseline and at 1-month and 4-month follow-up time points. We anticipate that results from this study will provide key data for all measures so that they can be included in future longitudinal studies and clinical trials.

For more information about this research study, please  view a summary  (PDF).

Results of the Study

No results will be returned to participants

How to Enroll

Patient opt-in and healthcare provider referrals accepted (Patients may self-enroll)

Please contact the PTEN clinical research team at 216.445.5850 or pten@ccf.org. A member of the research staff will get in touch to explain what is involved in study participation and how we conduct informed consent.