Program Schedule

Inheritance Patterns in Periodic Fever, Aphthous Stomatitis, Pharyngitis, and Adenitis Syndrome

Session: Oral Abstract Session: Characterizing Genetic and Clinical Factors in Pediatric Infectious Diseases
Thursday, October 9, 2014: 10:30 AM
Room: The Pennsylvania Convention Center: 107-AB

Background: Familial cases of periodic fever, aphthous stomatitis, pharyngitis, and adenitis syndrome (PFAPA) have been reported, but inheritance patterns have not been comprehensively evaluated. In this study, we characterize transmission patterns in a large cohort of PFAPA cases.

Methods: Medical records of patients seen at Vanderbilt Medical Center from 2000-2013 with ICD-9 diagnoses of recurrent fever were reviewed to identify patients with both (1) a diagnosis of PFAPA and (2) a family history of recurrent fever. These patients and their family members were contacted by phone to obtain symptom histories and construct 3-generation pedigrees with a structured questionnaire. Investigators reviewed questionnaires to classify subjects as having definite, probable, possible, or unlikely PFAPA based on defined criteria. Only those with definite or probable PFAPA were included in the analysis.

Results: Identification of probands is shown in Figure 1. Of 171 patients with PFAPA, we identified 14 probands with at least one family member with definite or probable PFAPA. In these 14 families, a total of 31 subjects met criteria for definite or probable PFAPA. Male to female ratio was 1.38:1. Affected cases had a total of 30 siblings of whom 7 had PFAPA and 48 parents of whom 6 had PFAPA (2 male-to-male transmission). Affected siblings had 86% concordance in having aphthous ulcers during episodes and a significant correlation in age of episode onset (Spearman's r=0.82, p=0.03). Parent-child pairs had 57% concordance in having aphthous ulcers and no correlation in age of onset (Spearman's r=0.11, p=0.81). Ten families (71%) had members without PFAPA who had aphthous ulcers.

Conclusion: In familial cases, PFAPA transmission is most consistent with autosomal dominant inheritance, but autosomal recessive and multifactorial modes cannot be excluded. Siblings have higher concordance in episode characteristics than parent-child pairs. The high prevalence of aphthous ulcers in family members of PFAPA patients suggests a commonality in the pathogenesis of aphthous ulcers and PFAPA. Familial aggregation does not prove genetic influence, but genomic interrogation of these families may provide more conclusive evidence of genetic involvement in PFAPA.


Kalpana Manthiram, MD1, Thomas Morgan, MD2 and Kathryn Edwards, MD, FIDSA1, (1)Division of Pediatric Infectious Disease, Vanderbilt University Medical Center, Nashville, TN, (2)Division of Medical Genetics and Genomic Medicine, Vanderbilt University Medical Center, Nashville, TN


K. Manthiram, None

T. Morgan, None

K. Edwards, Novartis: Grant Investigator and Scientific Advisor, Research grant

Previous Abstract | Next Abstract >>

Findings in the abstracts are embargoed until 12:01 a.m. EDT, Oct. 8th with the exception of research findings presented at the IDWeek press conferences.

Sponsoring Societies:

© 2014, All Rights Reserved.

Follow IDWeek