A case of Wolf-Hirschhorn syndrome and hypoplastic left heart syndrome.

Wolf-Hirschhorn Syndrome (WHS) is a genetic syndrome that includes a typical facial appearance, mental retardation, growth delay, seizures, and congenital cardiac defects. A deletion of the terminal band of the short arm of chromosome 4, with a breakpoint at the 4p15 to 4p16 region, is the most common genetic mutation causing WHS. Congenital heart disease associated with WHS typically includes atrial and ventricular septal defects, though there are a few case reports of associated complex congenital heart disease. Here we report a case of an infant with a large 4p deletion, with a breakpoint at the 4p12 region, and hypoplasic left heart syndrome. We discuss a possible link between the size of the chromosomal deletion in WHS and the severity of the cardiac defect.

Cochlear implantation in deafness-dystonia-optic neuronopathy (DDON) syndrome.

To report the results of the first known cochlear implantation in a patient with deafness-dystonia-optic neuronopathy (DDON) syndrome (Mohr-Tranebaerg syndrome, DFN-1). DDON syndrome is an X-linked condition characterized by postlingual sensorineural hearing loss in early childhood followed by dystonia, psychosis, and optic atrophy in adolescence and adulthood. The gene responsible for the condition maps to Xq22 adjacent to the gene causally related to X-linked agammaglobulinemia. The audiometric characteristics of DDON syndrome are typical of auditory neuropathy, with spiral ganglion cells being the suspected site of pathology. Performance following cochlear implantation in auditory neuropathy patients is variable and has yet to be reported in any patients with DDON syndrome. The reported case describes a male initially diagnosed with X-linked agammaglobulinemia due to recurrent infections. Speech, language and hearing were typical of a child in the first year of life; however profound hearing loss developed and cochlear implantation was performed at age 4. Following implantation, further genetic workup determined that the patient carries a deletion that includes BTK and DDP1/TIMM8a, consistent with the diagnosis of X-linked agammaglobulinemia and DDON syndrome. The patient's performance with the cochlear implant was marginal even after 2 years of use, with continued poor scores in standardized speech, language and audiometric tests. Additionally, his most-comfortable-level implant setting requires higher-than-normal current applied to the electrode array. This case report supports other studies showing that DDON syndrome results in an auditory neuropathy. Further investigation is required to determine the efficacy of cochlear implantation in this patient population. DDON syndrome should be considered in patients with X-linked agammaglobulinemia and hearing loss.