Findings, Phenotypes, Diagnostic Accuracy, and Treatment in Freeman-Burian Syndrome

Freeman-Burian syndrome (FBS) is a rare congenital myopathic craniofacial syndrome. Since publication of the genotype-correlated clinical diagnostic criteria, no complete survey of the literature has been accomplished. As part of the clinical practice guideline development, we evaluate diagnostic accuracy for FBS from 1938 to 2019 and range of findings, complications, treatments, and outcomes. Published manuscripts in PubMed, Google Scholar, and OMIM describing cases with a reported diagnosis of FBS, Sheldon-Hall syndrome, and distal arthrogryposes type 1 and 3 are initially included. Articles with sufficient case-level data for diagnosis verification are analyzed further. Of 724 unique papers considered, 188 papers describing 304 unique patients are included; 101 papers and 119 patients reflect an FBS diagnosis, with 80 patients meeting the full diagnostic criteria. Most cases are re-screened as distal arthrogryposis type 1. Among all cases re-screened as FBS, the presence of FBS pathognomonic craniofacial findings is not correlated with other physical findings. There are no significant differences between patients meeting the full diagnostic criteria and those not, but both are distinct from other diagnoses. Plastic surgery demonstrates the highest cumulative diagnostic accuracy for FBS overall (86.66%), while orthopedic surgery shows the lowest (44.83%). No statistically usable treatment-related or psychosocial data are available. Quality of case reports and patient data vary widely, reducing the statistical strength and significance. Major knowledge gaps exist in treatment, psychosocial, and longitudinal outcomes. At this point, it is impossible to derive clinical practice guidelines exclusively from the literature.