Extracephalic manifestations of nonchromosomal, nonsyndromic holoprosencephaly. Issue 2 (15th May 2018)

• Record Type: Journal Article
• Authors: Martinez, Ariel F.; Kruszka, Paul S.; Muenke, Maximilian
• Other Names: Kruszka Paul S. guestEditor.; Solomon Benjamin D. guestEditor.; Muenke Maximilian guestEditor.
• Is Part Of: American journal of medical genetics. Volume 178:Issue 2(2018)
• Page Start: 246
• Page End: 257
• Publication Date: 2018-05-15
• Subjects: congenital heart defect -- extracephalic manifestations -- fatty liver disease -- gastrointestinal anomaly -- genitourinary anomaly -- holoprosencephaly -- NAFLD -- neural tube defect -- SHH pathway -- skeletal anomaly; Medical genetics -- Periodicals; 616.04205
• DOI: 10.1002/ajmg.c.31616
• Languages: English
• ISSNs: 1552-4868

Abstract

Abstract : Nonchromosomal, nonsyndromic holoprosencephaly (NCNS‐HPE) has traditionally been considered as a condition of brain and craniofacial maldevelopment. In this review, we present the results of a comprehensive literature search supporting a wide spectrum of extracephalic manifestations identified in patients with NCNS‐HPE. These manifestations have been described in case reports and in large cohorts of patients with "single‐gene" mutations, suggesting that the NCNS‐HPE phenotype can be more complex than traditionally thought. Likely, a complex network of interacting genetic variants and environmental factors is responsible for these systemic abnormalities that deviate from the usual brain and craniofacial findings in NCNS‐HPE. In addition to the systemic consequences of pituitary dysfunction (as a direct result of brain midline defects), here we describe a number of extracephalic findings of NCNS‐HPE affecting various organ systems. It is our goal to provide a guide of extracephalic features for clinicians given the important clinical implications of these manifestations for the management and care of patients with HPE and their mutation‐positive relatives. The health risks associated with some manifestations (e.g., fatty liver disease) may have historically been neglected in affected families.