Pallister-Hall-like syndrome (PHLS) is a pleiotropic autosomal recessive disorder characterized by phenotypic variability. Patients exhibit postaxial polydactyly as well as hypothalamic hamartoma, cardiac and skeletal anomalies, and craniofacial dysmorphisms. Hirschsprung disease has also been observed (Rubino et al., 2018; Le et al., 2020). Pallister-Hall syndrome (146510) is an autosomal dominant disorder with features overlapping those of PHLS, caused by mutation in the GLI3 gene (165240).

A single maxillary central incisor positioned in the midline with morphological symmetry of the crown and bordered by lateral incisors.

This syndrome has characteristics of anophthalmia or microphthalmia, retinal dystrophy, and/or myopia, associated in some cases with cerebral anomalies. It has been described in two families. Polydactyly may also be present. Linkage analysis allowed identification of mutations in the BMP4 gene, which has already been shown to play a role in eye development.

RHYNS syndrome is characterized by gaze palsy, retinitis pigmentosa, sensorineural hearing loss, hypopituitarism, nephronophthisis, and mild skeletal dysplasia (Di Rocco et al., 1997).

Combined pituitary hormone deficiency-3 (CPHD3) is an autosomal recessive disorder characterized by hypopituitarism with structural anterior pituitary defects and cervical abnormalities with or without restricted neck rotation. Some patients have sensorineural hearing loss (summary by Rajab et al., 2008). For a discussion of phenotypic and genetic heterogeneity of combined pituitary hormone deficiency, see CPHD1 (613038).