Evidence-based Guidelines and Systematic Evidence Reviews currently in development


Title

Cancer Risk in Intersex/Differences of Sex Development (SER and EBG)

Workgroup Members

SER: Ina Amarillo (Chair), Aya Abu-El-Haija (PP&G Committee Liaison), Karen David, Mohammad Eldomery, Carmen Garrido, Joanna Gell, Shivani Golem, Xiaolin Hu, Tiffany Guess, Camilia Kamoun, J Whitehead


EBG: Louisa Pyle (Chair), Aya Abu-El-Haija (PP&G Committee Liaison), Margaret Adam, Marissa Adams, Sara Akhavanfard, Barbara Chubak, Veronica Gomez-Lobo, Frances Grimstad, Fen Guo, Charu Kaiwar, Wahab Khan, Esther Knapp, Jun Liao, Deqiong Ma, Stephan Mills, Chanika Phornphutkul, Sam Sharpe

Description

Differences of Sex Development/Intersex (DSD/I) traits is a broad diagnosis including individuals with atypicality of any of the four parameters of biological sex: sex chromosomes, sex hormones, gonads, and internal or external genitalia. A subset of these individuals have a predisposition to germ cell tumor (GCT) of the gonads. More than 90% of cases have a genetic cause of which 50-60% can be identified in practice. Emerging evidence has been able to link genetic cause with general DSD/I phenotypes and GCT predisposition. Some associations are clear – e.g., no association between 46,XX classical congenital adrenal hyperplasia with ambiguous/nonbinary genitalia and GCT – whereas other associations are less clear – e.g., NR5A1, DMRT1, or MAP3K1 46,XY DSD/I and GCT – possibly because most cases are included in large cohort studies with limited phenotyping and genetic evaluation. In the case of some genes (e.g., 46,XY DSD/I with AR loss-of-function), there was historically thought to be a clear association with high risk of GCT, but modern genotype-phenotype evaluations suggest a variant/risk correlation that results in decreased gonadectomy for these individuals.

Status: SER is in title and abstract screening training. EBG is in GRADE training.

 

Title

Diagnosis and Management of Fatty Acid Oxidation Disorders (SER and EBG)

Workgroup Members

SER: Amarilis Sanchez-Valle (Chair), Jerry Bedoyan, Amy Calhoun, Mari Mori (PP&G Committee Liaison), Wendy Smith, Elaine Spector, Ting Wen


EBG: Chanika Phornputkul (Co-chair), Ayper Tolun (Co-chair), Josh Baker, Kristina Cusmano-Ozog, Melanie Gillingham, Stephanie Harry, Yu Leng Phua, Rong Mao, Mari Mori (PP&G Committee Liaison), Alexandra Salser, Zohra Shad, Jerry Vockley

Description

The Topic Selection Committee (TSC) approved this topic to move forward following methodological review and consensus by the TSC. This topic was originally proposed to evaluate only long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency (LCHAD). Preliminary methodological review of the topic identified two potentially relevant systematic evidence reviews and several randomized controlled trials. Given the evidence base, it was determined there would be sufficient evidence to move forward with a SER/EBG encompassing all fatty acid oxidation disorders (FAOD), using the published SERs to streamline the process and serve as templates for the other FAODs.

Status: SER is finalizing full text review. EBG is in GRADE training.

 

Title

Diagnosis and Perinatal Management of Fetal Skeletal Dysplasias (SER and EBG)

Workgroup Members

SER: Mythily Ganapathi (Chair), Amal Alhashem, Lorraine Dugoff (PP&G Committee Liaison), Kristen Miller, Raul Pina-Aguilar, Marwan Shinawi, Monica Wojcik


EBG: Julie Hoover-Fong (Chair), Neha Bhatia, Jane Corteville, Lorraine Dugoff (PP&G Committee Liaison), Colleen Gioffreda, Kelsie Hankins, Nancy Hendrix, Erica Macke, Jessica Smith, Lea Tuzovic

Description

"Guidelines for the prenatal diagnosis of fetal skeletal dysplasias” (FSD) was published in 2009 and focused on prenatal diagnosis, pregnancy management, and delivery for individuals with FSD. Since the 2009 document was published, additional research has identified nearly 100 additional FSDs and refined the genetic contributions to the disorder. Newer prenatal and diagnostic testing methods are available and there are clinical trials underway for new treatments for some forms of FSD (e.g., achondroplasia). Following preliminary methodologist review, there is sufficient evidence to update the existing guideline to a systematic evidence review (SER) and evidence-based guideline (EBG) project.

Status: SER is conducting the literature search. EBG is in GRADE training.

 

Title

Diagnosis of Patients with Autism Spectrum Disorder (SER and EBG)

Workgroup Members

SER: Mafalda Barbosa (Co-chair), Elizabeth Spiteri (Co-chair), Danielle Baribeau, Abigail Kacpura, Jaime Lopes, Sonal Mahida, Dee McKnight, Mark Orland, Priya Prasad (PP&G Committee Liaison), Laura Sack, Michael Segal, Sherin Shaaban, Madina Sukhanova, Mary Wong, Catherine Ziats


EBG: Melissa Crenshaw (Co-chair), John Graham (Co-chair), Pam Feliciano, Philip Giampietro, Nathan Leu, Deqiong Ma, David Murdock, Priya Prasad (PP&G Committee Liaison), Beth Sheidley, Siddharth Srivastava, Kristen Wigby, Valerie Willis

Description

The Topic Selection Committee (TSC) approved this topic to move forward following methodological review and consensus by the TSC. This topic was originally proposed to evaluate only the use of chromosomal microarray (CMA) in patients with autism spectrum disorder (ASD), given the difficulty of clinicians to obtain insurance reimbursement for CMA. After significant discussion, the TSC determined that broadening the topic to evaluate the diagnostic and clinical utility of genetic testing more generally (e.g., including exome and genome sequencing and multigene panels) would be of greater benefit to ACMG membership, treating providers, and patients. Of note, the exclusion of patients with ASD was a significant limitation identified by both SER workgroup members and reviewers of the 2020 ACMG exome and genome sequencing for pediatric patients with congenital anomalies evidence review, which this SER/EBG will address. Preliminary methodological review of the topic identified multiple potentially relevant SERs and evidence-based guidelines which the SER and EBG workgroups can use to streamline the SER and EBG process; however, the SER team is larger than normal given the substantial amount of literature the workgroup will need to screen.

Status: SER is in title and abstract screening training. EBG is in GRADE training.

 

Title

Genetic Diagnosis and Clinical Management of Inherited Retinal Disorders (SER and EBG)

Workgroup Members

SER: Bin Guan (Chair), Sucheta Bhatt (PP&G Committee Liaison), Avinash Dharmadhikari, Arlene Drack, Abdallah Elias, Kristy Lee, Brittni Scruggs, Rachel Yiu


EBG: Robert Hufnagel (Chair), Sucheta Bhatt (PP&G Committee Liaison), Kari Branham, Milam Brantley, Carleton Bulkin, Robin Clark, Erin Conboy, Natario Couser, Alina Dumitrescu, Lonneke Haer-Wigman, Jun Liao, Cassie Mintz (PP&G Committee Liaison), Debarshi Mustafi, Kaitlin O’Connell, Tamara Roman, Lisa Schimmenti, Panagiotis Sergouniotis, Alpa Sidhu, Anne Slavotinek

Description

The purpose of this project is to systematically assess the utility of molecular genetic testing methods with respect to the diagnosis and clinical management of inherited retinal disorders (IRDs). Recent literature suggests that genome or clinical exome sequencing with copy number variant analysis results in a higher diagnostic yield, faster time to diagnosis, and access to gene-specific clinical trials when compared to panel testing, next-generation sequencing, or Sanger sequencing. This systematic evidence review will help standardize diagnostic practices for ophthalmologists and medical geneticists caring for populations with an IRD.

Status: SER is conducting the literature search. EBG is in GRADE training.

 

Title

Genetic Diagnosis and Clinical Management of Marfan Syndrome (SER and EBG)

Workgroup Members

SER: Rocio Moran (Chair), Shreyas Bellur, Jirat Chenbhanich, Mauricio De Castro (PP&G Committee Liaison), Berit Kerner, Mitzi Murray, Laura Pisani, Gabriela Repetto


EBG: Mauricio De Castro (Chair, PP&G Committee Liaison), Alan Braverman, Maya Brown-Zimmerman, Caitlin Chang, Hal Dietz, Josephine Grima, Merin Jose, Gretchen MacCarrick, Aleksandar Rajkovic, Rosemarie Smith, Xiangling Wang, Bo Yuan

Description

The purpose of this project is to review and update an existing document regarding the evaluation of the adolescent or adult with some features of Marfan syndrome. The document is over 10 years old and much has changed in the field regarding molecular and clinical diagnosis of Marfan syndrome and related disorders. These changes have the potential to change clinical practice; making a specific molecular diagnosis has therapeutic and management implications.

Status: SER is conducting the literature search. EBG is in GRADE training.

 

Title

Genetic Diagnosis and Clinical Management of Pompe Disease (SER and EBG)

Workgroup Members

SER: Chen Yang (Chair), Kerri Bosfield, Taraka Donti, Angelika Erwin, Jaya Ganesh, Christina Grant, Mari Mori (PP&G Committee Liaison), Priya Kishnani, Sarada Gandhi Kolli, Jie Liu, Wanqiong Qiao


EBG: Judith Hobert (Chair), Deeksha Bali, Bharatendu Chandra, Jennifer Cohen, Rachel Fisher, Marta Frigeni, Jaya Ganesh, Tiffany House, Shibani Kanungo, David Kronn, Mari Mori (PP&G Committee Liaison), Pillai, Natalie Shallow, Brian Shayota

Description

We propose an update of the 2006 American College of Medical Genetics and Genomics (ACMG) practice guideline entitled “Pompe disease diagnosis and management guideline”. Since its original publication, updated information has been published that examines diagnosis, treatment, and management strategies for Pompe disease. New research on advanced diagnostic technologies, emerging enzyme replacement therapies, and coordinated care have been added to the literature and a synthesis of this information would be integral in aiding clinicians treat individuals with Pompe disease. We propose conducting a systematic evidence review that will aid in the creation of an evidence-based guideline.

Status: Preliminary Board approval.

 

Title

Genetic Implications of Advanced Paternal Age: Evaluation and Recommendations (SER and EBG)

Workgroup Members

SER: Aleksandar Rajkovic (Chair), Katie Anderson, Yavuz Bayram, Robert Best, Yang Cao, Sau Wei Cheung, Jeffrey Dungan (PP&G Committee Liaison), Saurav Guha, Sherin Shaaban


EBG: Jeffrey Dungan (Co-chair, PP&G Committee Liaison), Dallas Reed (Co-chair, PP&G Committee Liaison), Paula Amato, Elena Ashkinadze, Lucy Chen, Lorraine Dugoff, Dolores Lamb, Reymundo Lozano, Helga Toriello

Description

We propose an update of the 2008 ACMG practice guideline entitled “Statement on guidance for genetic counseling in advanced paternal age”. Since its original publication, a substantial amount of new information has been published that addresses the impact of paternal age on a number of reproductive and childhood outcomes. Although there is no universally accepted definition of advanced paternal age (APA), most papers use age 40 or 45 years as a threshold age. In the U.S., about 10% of new fathers are >40 years old. While advancing paternal age is frequently paired with advancing maternal age, this is not true for all couples, or all reproductive scenarios. Many couples of APA seek out assisted reproductive technologies (ART). Because geneticists and genetic counselors are frequently called upon to provide advice and guidance to couples with a father >40 years of age, this update is timely and needed.

Status: SER is conducting the literature search. EBG is in GRADE training.

 

Title

Genetic Testing in Kidney Disease (SER and EBG)

Workgroup Members

SER: Christie Thomas (Co-chair, PP&G Committee Liaison), Xiangling Wang (Co-chair), Vimla Aggarwal, Stephanie Balow, Linnea Baudhuin, Yasar Caliskan, Yuan Ji, Haiying Meng, Binu Porath, Cong Wang, Ying Zou


EBG: Lakshmi Mehta (Co-chair), Christie Thomas (Co-chair, PP&G Committee Liaison), Reza Bekheirnia, Yu-Wei Cheng, Balram Gangaram, Mathieu Lemaire, Sarah Mazzola, Korbinian Reidhammer, Andre Weinstock

Description

Monogenic kidney disease may be seen in as many as 10% of a random sample of older adults on dialysis and nearly 40% in populations suspected of having genetic disease. However, genetic kidney disease is often unrecognized especially when it presents at an older age, occurs in the absence of a family history, or has a renal-limited presentation. Identification of the genetic basis of disease has several potential advantages including clarification of the diagnosis, predicting prognosis, anticipation of extrarenal presentations, directing genetic variant guided therapy and in the case of kidney transplant recipients, optimizing perioperative management, predicting disease recurrence, and permitting the evaluation of related living donors and other asymptomatic family members.

Status: Introduction to the SER and EBG process.

 

Title

Pre-symptomatic Screening of Living Kidney Donors for Monogenic Kidney Disease (SER and EBG)

Workgroup Members

Christie Thomas (Co-chair, PP&G Committee Liaison), Reza Bekheirnia (Co-chair), Deborah Adey, Margaret Freese, Malek Kamoun, Mathieu Lemaire, Lakshmi Mehta, Xiangling Wang

Description

End Stage Kidney Disease (ESKD) can be managed with long term dialysis or by kidney transplantation from deceased or living donors. Living kidney donors (LKD) have an increased long-term risk of ESKD post-donation. A donor that is a biological relative of the allograft recipient is at a higher risk of ESKD when compared to unrelated LKDs. There is substantial variation in ESKD risk across different ancestries and recipient-donor relationships. The magnitude of this risk in some exceeds that of other known risk factors for kidney disease (e.g., low birth weight, elevated BMI, hypertension). These data suggest that unrecognized, pre-symptomatic monogenic kidney disease may at least partly account for this risk. In fact, there are anecdotal reports of donors presenting after donation with the same disease as the recipient.

Status: Document in development.

Title

Rapid Exome and Genome Sequencing in the Neonatal and Pediatric Intensive Care Units (SER and EBG)

Workgroup Members

SER: Bimal Chaudhari (Chair), Elizabeth Barnby, Subit Barua, Gregory Costain, Akanchha Kesari, Paul Kruszka (PP&G Committee Liaison), Rong Mao, Bree Martin, Nifang Niu, Stefan Rentas, Laura Sack, Erica Sanford Kobayashi, Cristy Stagnar, Sofia Torreggiani


EBG: Rebecca Burke (Co-chair), Paul Kruszka (Co-chair, PP&G Committee Liaison), Sawona Biswas, Kyle Brothers, Matthew Ellinwood, Gilda Garza-Mayen, Saumya Jamuar, Marco Leung, Jun Liao, Catherine Rehder, Andrea Scheurer-Monaghan, Molly Schroeder, Ahmad Tayoun, Monica Wojcik, Yao Yang


Description

ACMG recently published its first evidence-based guideline (EBG) for exome/genome sequencing (ES/GS) for individuals with congenital anomalies and/or intellectual disability. However, since then, there has been a consistent appeal from members to specifically consider the utility of rapid ES/GS (rES/GS) in the NICU/PICU. Methodological review has found a growing evidence base, including some studies identified in the 2020 ACMG SER, with sufficient peer-reviewed publications and a substantial amount of supporting grey literature to develop an EBG specifically for this narrowly defined application of ES/GS.

Status: SER is conducting the literature search. EBG is in GRADE training.

 

Title

The Genetic Diagnosis and Clinical Management of Urea Cycle Disorders (SER and EBG)

Workgroup Members

SER: Sue Berry (Chair), Nicholas Ah Mew, Josh Baker, Lindsay Burrage (Therapeutics Committee Liaison), Renata Gallagher, Amarilis Sanchez-Valle, Kuntal Sen, Marwan Shinawi, Amanda Sonntag, Iveta Sosova, Sandesh Sreenath Nagamani, Huan Vuong


EBG: Brett Graham (Chair), Margo Breilyn, Lindsay Burrage (Therapeutics Committee Liaison), Sara Elsbecker, Andrea Gropman, Laura Konczal, Chung Lee, Erin MacLeod, H. Joel Mroczkowski, Emily Rohrer, Kara Simpson


Description

Urea cycle disorders are some of the most common inborn errors of hepatic metabolism. These disorders can be diagnosed in infancy through adulthood and affect more than 1 in 35,000 individuals. New therapies have been introduced in recent years (e.g., glycerol phenylbutyrate) and new complications are being recognized (e.g., liver disease, seizures, executive dysfunction and neuropsychiatric symptoms, etc.). Moreover, although liver transplantation was historically used primarily in neonatal onset cases, liver transplantation has become increasingly used in individuals even with late-onset disease. In addition, several nuances of acute management of hyperammonemic crisis (such as neuromonitoring with EEG) are being described, which are critical to improve mortality and morbidity. Thus, there are many recent advances that necessitate a practice guideline in this group of disorders.

Status: Introduction to the SER and EBG process.

 

Title

Update to Phenylalanine Hydroxylase Deficiency Diagnosis and Management: An Evidence-Based Clinical Guideline of the American College of Medical Genetics and Genomics (ACMG)

Workgroup Members

Jerry Vockley (Co-chair, Therapeutics Committee Liaison), Wendy Smith (Co-chair), Susan Berry, Kaitlyn Bloom, Christine Brown, Barbara Burton, Kim McBride (Therapeutics Committee Liaison), H. Joel Mroczkowski, Curt Scharfe


Description

The original ACMG Treatment Guideline was completed and published in 2013 and is in need of updating. A number of significant therapeutic options and important neurodevelopmental issues have received a lot of attention in the past few years. Key questions from the original guideline have been updated and 539 articles have been identified for review in the peer review scientific literature by the Medical Librarian. We now propose to create a workgroup to formally review this literature using current best practices for clinical guidelines in order to update the existing guideline and publish the findings. We will assemble a final panel of ~6 reviewers with experience in the field for this work.

Status: Draft to be circulated to the Therapeutics Committee and ACMG members for comment.