A review of Hallermann-Streiff syndrome demonstrates clinical overlap with other conditions.

Hallermann-Streiff syndrome (HSS) is a rare genetic condition characterized by seven cardinal findings comprising congenital cataracts, microphthalmia, recognizable facial features, sparse hair with hypotrichosis, skin atrophy, dental anomalies, and short stature. Around 200 patients have been reported and almost all cases have been sporadic. Several reviews have described the clinical findings in patients reported to have HSS, but the lack of a genetic test or other biomarker has complicated an accurate delineation of the condition. Although HSS is suspected to have a genetic basis and non-recurrent deleterious variants in genes such as GJA1, CHD6, and ZMPSTE24 have been noted in patients diagnosed with HSS, the etiology for almost all cases remains unknown. Our findings reveal a consistent phenotype but highlight the diagnostic challenges associated with HSS, including clinical overlap with other genetic conditions. It is also likely that the original reports of HSS described patients with heterogeneous conditions. Further research to identify the cause(s) of HSS and to develop best practices for patient care are needed.