The organizing centers for Drosophila imaginal disc development are created at straight boundaries between compartments; these are maintained by differences in cell affinity controlled by selector genes and intercellular signals. skuld and kohtalo encode homologs of TRAP240 and TRAP230, the two largest subunits of the Drosophila mediator complex; mutations in either gene cause identical phenotypes. We show here that both genes are required to establish normal cell affinity differences at the anteriorposterior and dorsal-ventral compartment boundaries of the wing disc. Mutant cells cross from the anterior to the posterior compartment, and can distort the dorsal-ventral boundary in either the dorsal or ventral direction. The Skuld and Kohtalo proteins physically interact in vivo and have synergistic effects when overexpressed, consistent with a skuld kohtalo double-mutant phenotype that is indistinguishable from either single mutant. We suggest that these two subunits do not participate in all of the activities of the mediator complex, but form a submodule that is required to regulate specific target genes, including those that control cell affinity.

Klippel-Feil sequence (KFS) is a rare congenital condition that presents with congenital cervical spine fusion, reduced cervical spine flexion, and low posterior hairline. Chiari malformation type 1 and sleep-disordered breathing (SDB) are frequent comorbidities of KFS. The pathologic basis of the connection between Chiari malformation type 1 and SDB in the setting of KFS is not clearly understood. Here we report a pediatric patient with KFS, SDB, and drooling who also had Chiari malformation type 1. Posterior fossa decompression of this patient significantly improved most symptoms including sleep disturbances. Repeat polysomnogram 8 weeks after posterior fossa decompression revealed worsening central sleep apnea despite the patient being clinically asymptomatic. Taken together, this case highlights the point that, although it is critical to recognize the association of SDB in the setting of KFS, decompression alone may not be sufficient to completely alleviate SDB and certain neurologic symptoms.

Introduction Klippel- Feil Sequence (KFS) is a rare congenital condition that classically presents with a triad of congenital cervical spine fusion, reduced cervical spine flexion and low posterior hairline. KFS has been associated with several comorbidities including congenital heart defects, hearing loss, renal dysfunction, Chiari malformation and sleep disordered breathing (SDB). The co-occurrence of SDB and chiari malformation type 1 (CM1) has been reported in multiple individuals. However, the pathological basis of the connection between CM1 and SDB in the setting of KFS is not clearly understood. Report of Case Here we present a pediatric case report of a patient with KFS, SDB, drooling and dysphagia. The drooling and dysphagia prompted an MRI that revealed CM1. Baseline polysomnogram (PSG) showed mild central sleep apnea with apnea-hypopnea index (AHI) 6.06 comprised of central apnea index 4.81 and obstructive apnea index 1.28. Posterior fossa decompression of this patient, following neurology recommendations, resolved majority of the symptoms, namely the drooling, nocturnal cough, dysphagia and sleep disturbances. However unexpectedly repeat polysomnogram eight weeks after posterior fossa decompression revealed worsening central sleep apnea despite the patient being clinically asymptomatic. Conclusion Taken together this case highlights the point that while it is critical to recognize the association of SDB in the setting of KFS, decompression alone may not be sufficient to completely alleviate SDB and/or certain neurological symptoms such as nocturnal coughing. Our observations are consistent with the hypothesis that SDB in a setting of KFS is multifactorial and pathophysiology is not clearly understood.