Yoshiko Hirano

BCOR analysis in patients with OFCD and Lenz microphthalmia syndromes, mental retardation with ocular anomalies, and cardiac laterality defects

Oculofaciocardiodental (OFCD) and Lenz microphthalmia syndromes form part of a spectrum of X-linked microphthalmia disorders characterized by ocular, dental, cardiac and skeletal anomalies and mental retardation. The two syndromes are allelic, caused by mutations in the BCL-6 corepressor gene (BCOR). To extend the series of phenotypes associated with pathogenic mutations in BCOR, we sequenced the BCOR gene in patients with (1) OFCD syndrome, (2) putative X-linked (‘Lenz’) microphthalmia syndrome, (3) isolated ocular defects and (4) laterality phenotypes. We present a new cohort of females with OFCD syndrome and null mutations in BCOR, supporting the hypothesis that BCOR is the sole molecular cause of this syndrome. We identify for the first time mosaic BCOR mutations in two females with OFCD syndrome and one apparently asymptomatic female. We present a female diagnosed with isolated ocular defects and identify minor features of OFCD syndrome, suggesting that OFCD syndrome may be mild and underdiagnosed. We have sequenced a cohort of males diagnosed with putative X-linked microphthalmia and found a mutation, p.P85L, in a single case, suggesting that BCOR mutations are not a major cause of X-linked microphthalmia in males. The absence of BCOR mutations in a panel of patients with non-specific laterality defects suggests that mutations in BCOR are not a major cause of isolated heart and laterality defects. Phenotypic analysis of OFCD and Lenz microphthalmia syndromes shows that in addition to the standard diagnostic criteria of congenital cataract, microphthalmia and radiculomegaly, patients should be examined for skeletal defects, particularly radioulnar synostosis, and cardiac/laterality defects.

Early two-stage double opposing Z-plasty or one-stage push-back palatoplasty?: comparisons in maxillary development and speech outcome at 4 years of age.

Determining the optimal timing and procedure of palatal surgery for children with cleft lip and palate has long raised a major controversy. An early two-stage palatoplasty protocol has been a recent trend in an attempt to obtain preferable maxillary growth without compromising adequate speech development. In this study, we aim to address whether the resulting maxillofacial growth and speech development obtained by an early 2-stage palatoplasty protocol are better than those obtained by conventional 1-stage push-back palatoplasty. Seventy-two nonsyndromic children with complete unilateral cleft lip and palate were enrolled in this study. They were divided into 2 groups: 30 children, who were treated with early 2-stage palatoplasty, in which soft palate closure was performed using a modified Furlows procedure at 12 months of age and hard palate closure was performed at 18 months of age (Early Tow Stage [ETS] group: 22 boys, 8 girls), and 42 children, who underwent 1-stage Wardill-Kilner push-back palatoplasty at 12 months of age (Push Back [PB] group: 31 boys, 11 girls). Cephalometric analysis for maxillofacial growth and assessments of speech development were performed for each child at 4 years of age. The ETS group showed a lager maxillary length than the PB group [anterior nasal spine (ANS)-ptm′: ETS, 46.7 ± 2.0 mm; PB, 43.6 ± 2.3 mm]. The ANS in the ETS group was positioned more anteriorly than that in the PB group (N′-ANS: ETS, 2.5 ± 1.8 mm; PB, 0.26 ± 2.5 mm), whereas the posterior edge of the maxilla positioned anteroposteiorly was comparable between the 2 groups. The anterior facial height was significantly greater in the ETS group than in the PB group (N-N′: ETS, 43.3 ± 2.9 mm; PB, 40.1 ± 2.3 mm, S-S′: ETS, 29.7 ± 3.2 mm; PB, 31.0 ± 3.2 mm). No statistically significant differences were observed in the incidence of either velopharyngeal incompetence or articulation errors between the 2 groups at 4 years of age. Our results show that the early 2-stage protocol is advantageous with regard to maxillary growth compared with 1-stage push-back palatoplasty without compromising speech development as evaluated for all children at 4 years of age.

Early Two-Stage Palatoplasty Using Modified Furlow's Veloplasty

Objective To achieve sufficient velopharyngeal function and maxillary growth for patients with unilateral cleft lip and palate (UCLP), the authors have designed a new treatment protocol for palate closure involving early two-stage palatoplasty with modified Furlow veloplasty. Details of the surgical protocol and the outcomes of the dental occlusion of patients at 4 years of age are presented. Design and Setting This was an institutional retrospective study. Patients Seventy-two UCLP patients were divided into two groups based on their treatment protocols: patients treated using the early two-stage palatoplasty protocol (ETS group; n = 30) and patients treated using Wardill-Kilner push-back palatoplasty performed at 1 year of age (PB group; n = 42). Interventions The features of the ETS protocol are as follows: The soft palate is repaired at 12 months of age using a modified Furlow technique. The residual cleft in the hard palate is closed at 18 months of age. Lip repair is carried out at 3 months of age with a modified Millard technique for all subjects. Results The ETS group showed a significantly better occlusal condition than the PB group. The incidence of normal occlusion at the noncleft side central incisor was 7.1% in the PB group; whereas, it was 66.7% in the ETS group. Conclusion The results indicate that the early two-stage protocol is advantageous for UCLP children in attaining better dental occlusion at 4 years of age.

Effect on Maxillary Arch Development of Early 2-Stage Palatoplasty by Modified Furlow Technique and Conventional 1-Stage Palatoplasty in Children With Complete Unilateral Cleft Lip and Palate

PURPOSE The purpose of this study was to evaluate the palatal morphology of patients with complete unilateral cleft lip and palate after early 2-stage palatoplasty (ETS) consisting of soft palate closure by a modified Furlow palatoplasty at 12 months of age and hard palate closure at 18 months of age. We compared the result with the palatal morphology obtained by Wardill-Kilner push-back palatoplasty (PB) at 12 months of age with that of children with noncleft palate. In the present study we investigated whether ETS can result in better palatal development than conventional PB. MATERIALS AND METHODS Thirty subjects were treated by ETS and 42 underwent PB. We also included cross-sectional data obtained from 66 children with noncleft palate as control. We measured the arch length, width, and cleft width using dental cast models that were consecutively taken at 3 months to 4 yrs of age and compared the results among the 3 groups. RESULTS At 4 years of age, the anteroposterior palatal length of ETS was significantly longer than that of PB by 9.8%, and the transversal palatal width of ETS was also markedly wider than that of PB at every point measured. Furthermore, ETS showed potential catch-up growth in the anteroposterior palatal length from 12 months to 4 years of age. CONCLUSION These results demonstrate that ETS has a considerable benefit for the palatal development of patients with complete unilateral cleft lip and palate compared with PB.