Expanding the Phenotypic Spectrum of Pathogenic KIAA0586 Variants: From Joubert Syndrome to Hydrolethalus Syndrome.

KIAA0586 variants have been associated with a wide range of ciliopathies, mainly Joubert syndrome (JS, OMIM #616490) and short-rib thoracic dysplasia syndrome (SRTD, OMIM #616546). However, the hypothesis that this gene is involved with hydrolethalus syndrome (HSL, OMIM #614120) and orofaciodigital syndrome IV (OMIM #258860) has already been raised. Ciliopathies' clinical features are often overlapped despite differing in phenotype severity. Besides KIAA0586, HYLS1 and KIF7 are also known for being causative of ciliopathies, indicating that all three genes may have similar or converging genomic pathways. Overall, the genotypic and phenotypic spectrum of ciliopathies becomes wider and conflicting while more and more new variants are added to this group of disorders' molecular pot. In this case report we discuss the first Brazilian individual clinically diagnosed with hydrolethalus syndrome and molecular findings that demonstrate the role of KIAA0586 as a causative gene of a group of genetic disorders. Also, recent reports on individuals with intronic and exonic variants combined leading to ciliopathies support our patient's molecular diagnosis. At the same time, we discuss variable expressivity and overlapping features in ciliopathies.

Laryngotracheomalacia in a Patient with Mosaic Trisomy 8.

Mosaic trisomy 8 is a condition characterized by a great phenotypic and cytogenetic variability whose incidence ranges around 1 in 25,000 to 50,000 live births. Here, we report a mosaic trisomy 8 patient presenting laryngotracheomalacia, an uncommon finding, analyzing its possible role over morbidity, and mortality. The patient was a boy who, after birth, had tachypnea and paleness. He presented periods of respiratory dysfunction with need of ventilatory support. Respiratory syncytial virus test was positive. Naso fibrobronchoscopy showed moderate laryngotracheomalacia. He also had recurrent episodes of pneumonia and difficulty in withdrawing continuous positive airway pressure. The patient also presented leucoma, abnormal and low-set ears, pectus excavatum, clenched fists with overlapping fingers, cryptorchidism, clubfeet, and deep longitudinal plantar creases. G-bands by Trypsin using giemsa (GTG-banding) karyotype from a peripheral blood sample revealed a mosaic trisomy 8: mos 47,XY, + 8[15]/46,XY[7]. At 4 months, the patient developed respiratory failure, and a chest computed tomography scan showed areas of atelectasis and gross fibroatelectatic striae. He ended up presenting clinical worsening and died at 4 months and 8 days. In our literature review, we found some reports describing patients with mosaic trisomy 8 and laryngotracheomalacia. However, we cannot rule out the possibility that this association could be casual, since laryngotracheomalacia is a relatively common finding in children. Therefore, more studies are still necessary to understand the possible relation between both conditions and the role of laryngotracheomalacia over morbidity and prognosis of mosaic trisomy 8 patients.