Original Paper

European Journal of Pediatrics

, Volume 169, Issue 4, pp 475-481

First online:

Open Access This content is freely available online to anyone, anywhere at any time.

Microcephaly, sensorineural deafness and Currarino triad with duplication–deletion of distal 7q

  • Piero PavoneAffiliated withUnit of Paediatrics, University Hospital “Vittorio Emanuele”
  • , Martino RuggieriAffiliated withUnit of Clinical Paediatrics, Department of Paediatrics, University of CataniaInstitute of Neurological Science (ISN), Italian National Research Council (CNR) Email author 
  • , Ilaria LombardoAffiliated withUnit of Clinical Paediatrics, Department of Paediatrics, University of Catania
  • , Jyotsna SudiAffiliated withDepartment of Cancer Genetics, Roswell Park Cancer InstituteDepartment of Cancer Prevention and Population Science, Roswell Park Cancer Institute
  • , Roberta BiancheriAffiliated withChild Neurology Unit, Gaslini Hospital, University of Genoa
  • , Danilo Castellano-ChiodoAffiliated withUnit of Clinical Paediatrics, Department of Paediatrics, University of Catania
  • , Andrea RossiAffiliated withNeuroradiology Unit, Gaslini Hospital, University of Genoa
  • , Gemma IncorporaAffiliated withUnit of Paediatrics, University Hospital “Arezzo-Paternò”
  • , Norma J. NowakAffiliated withDepartment of Cancer Genetics, Roswell Park Cancer InstituteDepartment of Cancer Prevention and Population Science, Roswell Park Cancer Institute
    • , Susan L. ChristianAffiliated withDepartment of Human Genetics, The University of Chicago
    • , Lorenzo PavoneAffiliated withUnit of Clinical Paediatrics, Department of Paediatrics, University of Catania
    • , William B. DobynsAffiliated withDepartment of Human Genetics, The University of Chicago

Abstract

Currarino syndrome (CS) is a peculiar form of caudal regression syndrome [also known as autosomal dominant sacral agenesis (OMIM no. 176450)] characterised by (1) partial absence of the sacrum with intact first sacral vertebra, (2) a pre-sacral mass and (3) anorectal anomalies (Currarino triad). We studied a 3-year-old girl with Currarino triad who had additional systemic features and performed array comparative genomic hybridisation to look for chromosomal abnormalities. This girl had the typical spectrum of anomalies of the CS including (a) partial sacral agenesis (hemisacrum with remnants of only sacral S1–S2 vertebrae and a residual S3 vertebral body) associated with complete coccygeal agenesis, (b) pre-intrasacral dermoid, (c) intra-dural lipoma, (d) ectopic anus and (e) tethered cord. She had, in addition, pre- and post-natal growth impairment (<3rd percentile), severe microcephaly (<−3 SD) with normal gyration pattern and lack of cortical thickening associated with a hypoplastic inferior vermis, facial dysmorphism, sensorineural deafness and decreased serum levels of IGF-1. A de novo 10.3-Mb duplication of 7q34–q35 and an 8.8-Mb deletion on 7q36 were identified in this patient. The Homeobox HLXB9 (CS) gene is contained within the deletion accounting for the CS phenotype including microcephaly. The spectrums of associated abnormalities in the IGF-1 deficiency growth retardation with sensorineural deafness and mental retardation syndrome (OMIM no. 608747) are discussed. To the best of our knowledge, this is the first reported case of a patient with distal 7q chromosomal imbalance and features of CS triad (including microcephaly) and the first documented case of a patient with normal gyration pattern microcephaly. The spectrum of associated anomalies in this newly recognised phenotype complex consists of growth failure, typical facial anomalies with additional (previously unreported) nervous system abnormalities (e.g. sensorineural deafness) and somatomedin C deficiency.

Keywords

Caudal regression syndrome Absence of sacrum Pre-sacral mass Anorectal anomalies Microcephaly Sensorineural deafness IGF-1 deficiency