International Journal of Pediatric Otorhinolaryngology 73S (2009) S2–S12 Genetic syndromes involving hearing Alessandro Martini a, *, Ferdinando Calzolari b , Alberto Sensi c a Audiology Department, Universitary Hospital, Ferrara, Italy b Neuroradiology Department, Universitary Hospital, Ferrara, Italy c Clinical Genetics, Universitary Hospital, Ferrara, Italy ARTICLE INFO ABSTRACT Keywords: Genetic syndromes Pediatric Hearing loss Objective: The fundamental processes involved in the mechanism of hearing seem to be controlled by hun- dreds of genes and hereditary hearing impairment may be caused by a large variety of genetic mutations in different genes. Approximately 150 loci for monogenic syndromic and non-syndromic hearing impairment (HI) disorders have been mapped to the human genome. The identification of these genes and functional analysis of the proteins they encode, are paving the way towards a better understanding of the physiology and pathophysiology of the auditory system. To date, approximately 50 causative genes have been identified. Methods: The clinical and neuroradioldical findings of syndromal hearing impairment are analysed. Results: This paper presents an updated report on genetic syndromes in which a hearing impairment is in- volved, with a particular attention to the ones associated with external ear and craniofacial malformations. Conclusions: Concepts in human genetics are rapidly evolving together with technologies. The concept itself of gene is changing. A genetic diagnosis of syndromal hearing impairment has many practical consequences: it can implies specific prognosis, specific management, specific recurrence risk in relatives and, if the diagnosis is confirmed at the molecular level, possibility of a specific early prenatal diagnosis for severe syndromes. It is important to highlight the necessity that the pediatric otolaryngologist must have a close collaboration with a clinical geneticist and a neuroradiologist. © 2009 Elsevier Ireland Ltd. All rights reserved. Contents 1. Introduction .................................................................................... S2 2. Genetic hearing loss associated to external ear anomalies and craniofacial malformations .................................... S4 3. Conclusion ..................................................................................... S10 References ..................................................................................... S10 1. Introduction Genetic hearing impairment (HI) may be congenital, early acquired (i.e., in the neonatal period) or acquired throughout child- hood, it also may develop however, at any time throughout life or deteriorate as part of a pre-existing congenital or acquired hearing impairment. In many cases, it is impossible to distinguish between genetic HI present at birth, or acquired in the neonatal period which is thus termed congenital. As genetic HI may develop before or after language acquisition some prefer to use the terms pre-lingual and postlingual HI. As language and speech development is essential for communication, the impact and adverse effects of a pre-lingual hearing impairment can be extremely damaging if not treated [1–3]. * Corresponding author: Prof. Alessandro Martini, Audiologia - Univ. di Ferrara, Corso Giovecca 203. 44100 Ferrara, Italy. E-mail address: mma2@unife.it (A. Martini). 0165-5876/$ – see front matter © 2009 Elsevier Ireland Ltd. All rights reserved. To date, more than 400 different genetic conditions associated with hearing impairment have been described. Over the past 15 years, hereditary diseases associated with hearing impairment have been mapped, and several genes have already been identified (see the Hereditary Hearing Loss homepage) [4]. A genetic diagnosis of syndromal HI has many practical con- sequences: it can imply specific prognosis, specific management, specific recurrence risk in relatives and, if the diagnosis is con- firmed at the molecular level, possibility of a specific early prenatal diagnosis for severe syndromes. Concepts in human genetics are rapidly evolving together with technologies. The concept itself of gene is changing. Roughly speaking, genes are the heritable units that influence traits. The Human Genome Nomenclature Organization defines a gene as a DNA segment that contributes to phenotype/function; however evidences of overlapping genes, alternative splicing, trans splicing, gene regulators located at long distances from the coding sequences and diffuse transcribing activities have challenged this definition,