Congenital Sensorineural Hearing Loss and Inborn Pigmentary Disorders: First Report of Multilocus Syndrome in Piebaldism

• Published in: Medicina (Kaunas, Lithuania) Lithuania), 2019-07, Vol.55 (7), p.345
• Main Authors: Gironi, Laura Cristina, Colombo, Enrico, Brusco, Alfredo, Grosso, Enrico, Naretto, Valeria Giorgia, Guala, Andrea, Di Gregorio, Eleonora, Zonta, Andrea, Zottarelli, Francesca, Pasini, Barbara, Savoia, Paola
• Format: Article
• Language: English
• Subjects: 15q13.3 deletion; auditory-pigmentary disorders; Case Report; Female; genetic skin disorders; genodermatoses; Hearing Loss, Sensorineural - genetics; Hearing Loss, Sensorineural - physiopathology; Humans; Male; Middle Aged; multilocus syndrome; neurocristopathies; piebaldism; Piebaldism - complications; Piebaldism - genetics; Piebaldism - physiopathology; Polymerase Chain Reaction - methods; Twins - genetics; Young Adult
• ISSN: 1648-9144; 1010-660X; 1648-9144; 1010-660X
• DOI: 10.3390/medicina55070345

Congenital sensorineural hearing loss may occur in association with inborn pigmentary defects of the iris, hair, and skin. These conditions, named auditory-pigmentary disorders (APDs), represent extremely heterogeneous hereditary diseases, including Waardenburg syndromes, oculocutaneous albinism, Tietz syndrome, and piebaldism. APDs are part of the neurocristopathies, a group of congenital multisystem disorders caused by an altered development of the neural crest cells, multipotent progenitors of a wide variety of different lineages, including those differentiating into peripheral nervous system glial cells and melanocytes. We report on clinical and genetic findings of two monozygotic twins from a large Albanian family who showed a complex phenotype featured by sensorineural congenital deafness, severe neuropsychiatric impairment, and inborn pigmentary defects of hair and skin. The genetic analyzes identified, in both probands, an unreported co-occurrence of a new heterozygous germline pathogenic variant (c.2484 + 5G > T splicing mutation) in the gene, consistent with the diagnosis of piebaldism, and a heterozygous deletion at chromosome 15q13.3, responsible for the neuropsychiatric impairment. This case represents the first worldwide report of dual locus inherited syndrome in piebald patients affected by a complex auditory-pigmentary multisystem phenotype. Here we also synthesize the clinical and genetic findings of all known neurocristopathies characterized by a hypopigmentary congenital disorder.