A male foal developing within a pregnant native Hokkaido mare presented with an abnormal bladder on gestational day 215 and was delivered by inducing parturition. Transabdominal ultrasonography indicated a bladder depth of >13 cm, with a wall-like structure bisecting the bladder. At 42 hr after birth, transnasal endoscopy revealed a cleft hard palate, and the foal was subsequently euthanized. A defect in the palatine process of the maxillary head and a large cyst connected to the bladder, although not continuous with the umbilicus, were identified by autopsy computed tomography and necropsy. The foal was accordingly diagnosed with a cleft median hard palate and urachal dysplasia.

Orofacial clefts (OFCs) are the most common craniofacial birth defects and are often categorized into two etiologically distinct groups: cleft lip with or without cleft palate (CL/P) and isolated cleft palate (CP). CP is highly heritable, but there are still relatively few established genetic risk factors associated with its occurrence compared to CL/P. Historically, CP has been studied as a single phenotype despite manifesting across a spectrum of defects involving the hard and/or soft palate. We performed GWAS using transmission disequilibrium tests using 435 case-parent trios to evaluate broad risks for any cleft palate (ACP, n=435), as well as subtype-specific risks for any cleft soft palate (CSP, n=259) and any cleft hard palate (CHP, n=125). We identified a single genome-wide significant locus at 9q33.3 (lead SNP rs7035976, p=4.24×10 -8 ) associated with CHP. One gene at this locus, angiopoietin-like 2 ( ANGPTL2 ), plays a role in osteoblast differentiation. It is expressed in craniofacial tissue of human embryos, as well as in the developing mouse palatal shelves. We found 19 additional loci reaching suggestive significance (p<5×10 -6 ), of which only one overlapped between groups (chromosome 17q24.2, ACP and CSP). Odds ratios (ORs) for each of the 20 loci were most similar across all three groups for SNPs associated with the ACP group, but more distinct when comparing SNPs associated with either the CSP or CHP groups. We also found nominal evidence of replication (p<0.05) for 22 SNPs previously associated with cleft palate (including CL/P). Interestingly, most SNPs associated with CL/P cases were found to convey the opposite effect in those replicated in our dataset for CP only. Ours is the first study to evaluate CP risks in the context of its subtypes and we provide newly reported associations affecting the broad risk for CP as well as evidence of subtype-specific risks.

Cleft palate (CP) is one of the most common craniofacial birth defects; however, there are relatively few established genetic risk factors associated with its occurrence despite high heritability. Historically, CP has been studied as a single phenotype, although it manifests across a spectrum of defects involving the hard and/or soft palate. We performed a genome-wide association study using transmission disequilibrium tests of 435 case-parent trios to evaluate broad risks for any cleft palate (ACP) (n = 435), and subtype-specific risks for any cleft soft palate (CSP), (n = 259) and any cleft hard palate (CHP) (n = 125). We identified a single genome-wide significant locus at 9q33.3 (lead SNP rs7035976, p = 4.24 × 10-8) associated with CHP. One gene at this locus, angiopoietin-like 2 (ANGPTL2), plays a role in osteoblast differentiation. It is expressed both in craniofacial tissue of human embryos and developing mouse palatal shelves. We found 19 additional loci reaching suggestive significance (p < 5 × 10-6), of which only one overlapped between groups (chromosome 17q24.2, ACP and CSP). Odds ratios for the 20 loci were most similar across all 3 groups for SNPs associated with the ACP group, but more distinct when comparing SNPs associated with either subtype. We also found nominal evidence of replication (p < 0.05) for 22 SNPs previously associated with orofacial clefts. Our study to evaluate CP risks in the context of its subtypes and we provide newly reported associations affecting the broad risk for CP as well as evidence of subtype-specific risks.

Cleft repair has been in constant evolution since its inception. Conventional repair of the cleft hard palate involves closure of nasal and oral mucosa without bony reconstitution. In many instances, this approach is adequate, but, particularly in complete clefts, the lack of bony support can lead to collapse of the maxillary arch, dental crowding, and posterior cross-bite. To address these shortcomings, our institution performs a two-staged palatoplasty with concomitant bone grafting of the alveolus and hard palate in the second stage. A retrospective review of children who underwent a two-staged palatoplasty at our institution was performed. These patients' records and images were reviewed for complications and changes in maxillary morphology. Fourteen patients with complete clefts had a two-staged palatoplasty with bone grafting in the second stage. The mean age at surgery was 37.5 months, and the mean follow-up was 16 months. One patient had resorption of the alveolar bone graft requiring additional bone grafting. The remaining patients were without complications and had good consolidation of the bone graft on follow-up imaging. Our early results support that there is a low complication rate (7% regrafting) in those patients who underwent bone grafting at the time of cleft palate repair with early evidence of bony consolidation on imaging and clinical examination. Wide exposure during the repair allows complete grafting of the maxillary bony deficit, which is not possible with traditional alveolar cleft repair and may alleviate the shortcoming of soft-tissue closure only. Future study is necessary to determine long-term outcomes.

The cleft palate is one of the most common congenital anomalies treated by plastic surgeons. The cleft width increases the tension of repair and necessitates excessive dissection that might affect maxillary growth. Decreasing the width of cleft minimize tension, dissection and may limit the impact on maxillary growth. The purpose of the study was to evaluate the effect of nasal layer closure of the hard palate at the time of cleft lip repair in patients with complete cleft lip and palate, to demonstrate the efficacy of narrowing the gap and to reduce the incidence of fistulae or other complications. Thirty patients less than 1 year of age were included in this prospective observational study. A superiorly based vomer flap was used to repair the nasal layer of the cleft hard palate at the time of primary cleft lip repair. 12-14 weeks after the vomer flap, the cleft soft and hard palate was definitively repaired. Alveolar and palatal gaps were recorded during the 1st and 2nd operations to demonstrate the reduction of the gap defect. The mean reduction of the alveolar cleft width in patients who had a vomer flap in the first stage was 4.067mm and the mean reduction of the palatal gap was 4.517mm. Only 3 patients developed small fistula on the repaired nasal layer that was discovered and corrected during definitive palatoplasty. Nasal layer closure is a simple surgical technique that can be used to close the hard palate at the time of cleft lip repair. It is a valuable addition to cleft lip and palate repair that may prevent some cleft palate surgical complications.