Cleft patients with Holoprosencephaly (HPE) constitute a controversy due to a variable facial appearance. HPE appearance varies from
only a columella to a prolabium‑premaxilla complex agenesis up to a common unilateral or bilateral cleft lip and palate with a single central
incisor, various brain deformities, and/or even normal brain development. It is challenging to designate such various appearances, to understand
their etiopathogenesis, and to choose the most appropriate management. Literature was reviewed for diagnostic criteria, pregnancy history, clinical
findings, brain development, survival rate, initial perioperative management, and postsurgical midfacial growth in cleft patients with HPE. The findings
were compared with a clinical database of 85 cleft patients with HPE at the Department of Maxillofacial and Oral Surgery, University of Pretoria.
AIMS OF PART 1: The aim of the study is to overcome disparities widely existing among clinicians regarding definitive diagnostic criteria, especially in
cases with a common appearance of a uni‑ or bilateral cleft lip alveolus or cleft lip, alveolus and palate deformity, and cases presenting facial structural
agenesis. MATERIALS AND METHOD : A literature search related to diagnostic criteria was compared to results of a cleft HPE database from a single
tertiary institution. RESULTS : HPE cleft cases can be allocated to one of the following subdivisions: (1) columella complex agenesis (Ag‑Colum), (2)
prolabium‑premaxilla‑columella complex agenesis in cleft lip‑alveolus deformities (Ag‑CLA), (3) prolabium‑premaxilla‑columella agenesis in cases
with complete cleft lip alveolus palate (Ag‑CLAP), and (4) standard type (holoprosencephaly in patients with a standard cleft) with uni‑ or bilateral
CLA or CLAP, hard and soft palate cleft (hPsP), and atrophic premaxillae, with or without single central incisor. Further, incidence, variation in
brain development, and appearances in HPE cleft patients of different races and gender, epilepsy, and early death are discussed. CONCLUSION : This
paper adds new data and facts to the existing literature related to cleft lip and palate patients suffering from HPE.