Holoprosencephaly–polydactyly/pseudotrisomy 13

Abstract

Patients with a combination of holoprosencephaly and polydactyly, but with apparently normal chromosomes, may be clinically diagnosed with holoprosencephaly–polydactyly syndrome (HPS), also termed pseudotrisomy 13. However, the criteria for HPS have been controversial since the advent of the diagnostic term, and a clear understanding of the condition lacks definitive delineation. We review the historical and current perspectives on the condition and analyze findings in 40 patients with apparent HPS, including cases from the literature and two previously unreported patients. Overall, our analysis suggests previously unrecognized trends in patients diagnosed with HPS. Specifically, there appears to be a higher prevalence of visceral anomalies, most significantly cardiac and genitourinary, but also with increased gastrointestinal, pulmonary, adrenal, skeletal, and renal abnormalities, in patients with HPS. Although these visceral anomalies may not be essential for the identification of HPS, clinicians should be aware of the presence of such characteristics in these patients to optimize management and help establish etiologies.

Syndromes associated with holoprosencephaly

“…Because HPE and polydactyly are features of trisomy 13, Hewitt et al suggested the term pseudotrisomy 13 for this presentation given the normal karyotype (Hewitt, Seller, Bennett, & Maxwell, 1989), and Cohen and Gorlin later “coined” the term pseudotrisomy 13 syndrome (Cohen & Gorlin, 1991). Bous et al reviewed 40 cases of pseudotrisomy 13 syndrome and reported 80% of cases with classic HPE (MRI evidence of HPE), 80% with polydactyly, and 58% with a cardiac anomaly (Bous et al, 2012). There is no known molecular diagnostic association and research with next generation sequencing is needed to more thoroughly interrogate pseudotrisomy 13 for a molecular diagnosis.…”