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

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.

Currarinos syndrom ved Rikshospitalet 1961 – 2012

“…This patient had a terminal deletion of chromosome 7q, which includes the MNX1 gene among others and which is known from the literature (32,33). A lower prevalence of mutations in sporadic cases of Currarino syndrome is consistent with previous observations, which have shown that mutations are present in the majority of familial cases, but in only 30 % of sporadic cases (10).…”

Etiology of Caudal Regression Syndrome

“…In addition, three studies have shown an association between chromosomal abnormalities 18p11.2 deletion and micro duplication at 22q11.21 and CRS, and between duplication-deletion of distal 7q and CS ( [79]. The deleted region contains 70 RefSeq genes including HLXB9, SHH and EN2, while the duplication contains82 genes ( Table 2).…”

4q27 deletion and 7q36.1 microduplication in a patient with multiple malformations and hearing loss: a case report

“…There are 4 reports of 4q deletions or 7q duplications with hearing impairment available in the literature. The four cases included a 8-year-old boy with deletion in 4q35.1q35.2 region [16], a male infant with deletion in 4q33q35 [17], a 3-year-old girl with duplication of 7q34q35 and deletion in 7q36 [18], and a girl with Complex rearrangement of 7q21.13-q22.1 [19], who were all having bilateral hearing loss with low-set ears (Table 1). Reviewing 141 cases in DECIPHER database showed that only a girl (DECIPHER ID: 293597) with mutations in SPATA5 (located in 4q28.1) and TSHR presented sensorineural hearing impairment.…”