SPECC1L regulates palate development downstream of IRF6.

SPECC1L mutations have been identified in patients with rare atypical orofacial clefts and with syndromic cleft lip and/or palate (CL/P). These mutations cluster in the second coiled-coil and calponin homology domains of SPECC1L and severely affect the ability of SPECC1L to associate with microtubules. We previously showed that gene-trap knockout of Specc1l in mouse results in early embryonic lethality. We now present a truncation mutant mouse allele, Specc1lΔC510, that results in perinatal lethality. Specc1lΔC510/ΔC510 homozygotes showed abnormal palate rugae but did not show cleft palate. However, when crossed with a gene-trap allele, Specc1lcGT/ΔC510 compound heterozygotes showed a palate elevation delay with incompletely penetrant cleft palate. Specc1lcGT/ΔC510 embryos exhibit transient oral epithelial adhesions at E13.5, which may delay shelf elevation. Consistent with oral adhesions, we show periderm layer abnormalities, including ectopic apical expression of adherens junction markers, similar to Irf6 hypomorphic mutants and Arhgap29 heterozygotes. Indeed, SPECC1L expression is drastically reduced in Irf6 mutant palatal shelves. Finally, we wanted to determine if SPECC1L deficiency also contributed to non-syndromic (ns) CL/P. We sequenced 62 Caucasian, 89 Filipino, 90 Ethiopian, 90 Nigerian and 95 Japanese patients with nsCL/P and identified three rare coding variants (p.Ala86Thr, p.Met91Iso and p.Arg546Gln) in six individuals. These variants reside outside of SPECC1L coiled-coil domains and result in milder functional defects than variants associated with syndromic clefting. Together, our data indicate that palate elevation is sensitive to deficiency of SPECC1L dosage and function and that SPECC1L cytoskeletal protein functions downstream of IRF6 in palatogenesis.

Topiramate-Induced Aqueous Misdirection in a Nanophthalmic Eye.

A 51-year-old female was referred to the emergency department with a one-day history of severe right eye pain, blurry vision, and conjunctival injection. A review of past ocular history was notable for nanophthalmos and narrow angles with patent peripheral iridotomies. Anterior segment exam findings were consistent with aqueous misdirection and a review of medications indicated recent topiramate initiation for headaches and depression. The acute attack was initially controlled with medical management and plans for future surgical intervention were made. Although ocular screening prior to initiation of topiramate is not recommended, this case highlights the importance of pre-screening in a patient with a pre-existing condition such as nanophthalmos. Additionally, this case addresses the ocular side effects of anti-depressants and the emerging relationship between glaucoma and depression. Appropriately addressing these issues and coordinating care with behavioral health providers has the potential to prevent optic nerve damage and loss of vision.

Pott's puffy tumor in a 23-month-old: Youngest known case of a rare disease.

This case report describes a child who developed Pott's puffy tumor and was treated at the Children's Mercy Hospital in Kansas City. In addition to a discussion of a case, a review of the literature was completed on this topic describing the typical embryology and development of the frontal sinus, and the epidemiology, diagnosis, and treatment of Pott's puffy tumor. The patient was a 23-month-old boy who developed Pott's puffy tumor after recovery from influenza. The patient presented to the hospital with progressing edema of the unilateral eye that spread bilaterally within a few days. A CT scan demonstrated pansinusitis, developed frontal sinuses, right periorbital cellulitis, and medial forehead subperiosteal abscess. Functional endoscopic sinus surgery and transcutaneous abscess drainage were urgently performed and the patient made a full recovery following a course of ertapenem and levofloxacin. The presence of a developed frontal sinus in a 23-month-old is an unexpected radiologic finding. This case represents the youngest patient reported in the literature to develop this rare complication of frontal sinusitis.