BACKGROUND: To report the presentation, diagnostic process, management and results of cochlear implantation of patients diagnosed with Bjornstad syndrome with profound sensorineural hearing loss (SNHL).
UNASSIGNED: A retrospective report of two siblings with Bjornstad syndrome suffering profound SNHL unresponsive to conventional hearing aids treated with bilateral simultaneous cochlear implantation.
METHODS: Tertiary-referral center.
RESULTS: Cochlear implant surgeries of two siblings (four ears) with profound SNHL and bilateral inner ear anomaly (incomplete partition type 1) were performed without complications. Postoperative audiometric measurements showed a significiant improvement in pure-tone threshold and a word recognition score. In the literature review, no previous case of Bjornstad syndrome treated with cochlear implantation has been reported.
CONCLUSIONS: Cochlear implantation is an effective, safe, and ultimate treatment option for Bjornstad syndrome with profound SNHL not responding to hearing aids.

Of the many types of mitochondrial diseases, mutations affecting BCS1L gene are regarded as chief cause of the defective mitochondrial complex-III, affecting normal mitochondrial functioning, and leading to wide variety of phenotypes.
In this case report we describe a novel genotype linked to a unique phenotype in a Saudi patient born of a consanguineous marriage. Detailed genetic analysis and whole genome sequencing identified a novel homozygous missense mutation in exon 5 c.712A > G (p.Ser328Gly) of the BCS1L gene, with predicted deleterious effects on the functioning AAA+-ATPase domain of the protein characterized by distinct clinical presentation associated with profound multisystem involvement, conductive hearing loss, absent external auditory canal, low posterior hair line, short neck, micro and retrognathia, over riding fingers, rocker bottom foot, small phallus with bilateral absent testis (empty scrotum) and intolerable lactic acidosis.
A pathogenic effect of this novel BCS1L mutation was reflected in the patient with his failure to thrive and a complex clinical and metabolic phenotype.

Pili torti is an extremely rare hair phenotype characterized by short length of hairs with hair shafts being easily broken. However, the mechanism of fragility in pili torti is unclear. In this study, we examined the underlying morphological features responsible for pili torti formation using transmission electron microscopy (TEM). We used pili torti samples from a patient with Björnstad syndrome and normal hairs from a healthy subject as a comparison. The macroscopic morphological features of the samples agreed with the results of a previous study showing that pili torti is twisted, flattened, thin and with partial trichorrhexis. Young\'s modulus of the samples was lower than that of normal hairs. Because the cross-sectional area of the pili torti samples was also smaller than that of normal hairs, it was clarified that the tensile strength of pili torti is 2.1-times lower than that of normal hair. Assessment of morphological features by TEM showed that the cuticle layers of the samples had wavy shapes with different thicknesses. Additionally, the cortex in the samples showed loose keratin intermediate filaments (IF). Our results suggested that these abnormalities in pili torti had already occurred below the infundibulum. Thus, the weakness of pili torti in tensile strength is thought to result from loose IF because of dysformation of disulfide bonds.

As a powerful tool to identify the molecular pathogenesis of Mendelian disorders, exome sequencing was used to identify the genetic basis of two siblings with hearing loss and hypotrichosis and clarify the diagnosis. No pathogenic mutations in GJB2, GJB3 and GJB6 genes were found in the siblings. By analysis of exome of the proband, we identified a novel missense (p.R306C) mutation and a nonsense (p.R186*) mutation in the BCS1L gene. Mutations were confirmed by Sanger sequencing. The siblings were compound heterozygotes, and the inheritance mode of autosomal recessive was postulated. BCS1L is the causative gene of Björnstad syndrome, which is characterized by sensorineural hearing loss and pili torti. The longitudinal gutters along the hair shaft were found by scanning electron microscopy in our patient. Therefore the diagnosis of Björnstad syndrome was eventually made for the patients. Our study extends the phenotypic spectrum of Björnstad syndrome and highlights the clinical applicability of exome sequencing as a diagnostic tool for atypical Mendelian disorders.