TY - JOUR
T1 - Congenital sensorineural hearing loss and inborn pigmentary disorders
T2 - First report of multilocus syndrome in piebaldism
AU - Gironi, Laura Cristina
AU - Colombo, Enrico
AU - Brusco, Alfredo
AU - Grosso, Enrico
AU - Naretto, Valeria Giorgia
AU - Guala, Andrea
AU - Di Gregorio, Eleonora
AU - Zonta, Andrea
AU - Zottarelli, Francesca
AU - Pasini, Barbara
AU - Savoia, Paola
N1 - Publisher Copyright:
© 2019 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2019/7
Y1 - 2019/7
N2 - 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 KIT 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.
AB - 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 KIT 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.
KW - 15q13.3 deletion
KW - Auditory-pigmentary disorders
KW - Genetic skin disorders
KW - Genodermatoses
KW - KIT
KW - Multilocus syndrome
KW - Neurocristopathies
KW - Piebaldism
UR - http://www.scopus.com/inward/record.url?scp=85069315964&partnerID=8YFLogxK
U2 - 10.3390/medicina55070345
DO - 10.3390/medicina55070345
M3 - Article
SN - 1010-660X
VL - 55
JO - Medicina (Lithuania)
JF - Medicina (Lithuania)
IS - 7
M1 - 345
ER -