OTOF-related deafness is characterized by two phenotypes: prelingual nonsyndromic auditory neuropathy spectrum disorder (ANSD) and, less frequently, temperature-sensitive auditory neuropathy spectrum disorder (TS-ANSD). OTOF-related ANSD is characterized by congenital or prelingual, typically severe-to-profound bilateral deafness without inner-ear anomalies on MRI or CT examination of the temporal bones. Otoacoustic emissions (OAEs) are present and auditory brain stem response is abnormal at birth. Newborn hearing screening testing of OAEs only will fail to detect this disorder in most individuals. OAEs may decrease or disappear with age in 20%-80% of individuals. TS-ANSD typically presents with normal-to-moderate hearing loss (0-55 dB) at baseline body temperature. An elevation of body temperature (approximately 0.5°C or more) triggers significant bilateral hearing loss ranging from severe to profound, with resolution of hearing loss typically occurring within hours of a return to baseline body temperature.

PCWH syndrome is a complex neurocristopathy that includes features of 4 distinct syndromes: peripheral demyelinating neuropathy (see 118200), central dysmyelination, Waardenburg syndrome, and Hirschsprung disease (see 142623) (Inoue et al., 2004). Inoue et al. (2004) proposed the acronym PCWH for this disorder.

Any autosomal recessive nonsyndromic deafness in which the cause of the disease is a mutation in the RIPOR2 gene.

SPTBN4 disorder is typically characterized by severe-to-profound developmental delay and/or intellectual disability, although two individuals in one family had a milder phenotype, including one individual with normal cognitive development. Speech and language skills are often severely limited. Affected individuals rarely achieve head control. Most are unable to sit, stand, or walk. Affected individuals typically have congenital hypotonia that may transition to hypertonia. Axonal motor neuropathy leads to hyporeflexia/areflexia and weakness, which can result in respiratory difficulties requiring ventilatory support. Most affected individuals require tube feeding for nutrition. Half of affected individuals develop seizures. Cortical visual impairment and auditory neuropathy have also been reported.