Albert K. Oh

Validity and Reliability of Craniofacial Anthropometric Measurement of 3D Digital Photogrammetric Images

Background: Direct anthropometry performed during a patient examination is the standard technique for quantifying craniofacial dysmorphology, as well as for surgical planning and outcome assessment. Several new technologies have been designed to computerize anthropometric measurements, including three-dimensional (3D) digital photogrammetry. These digital systems have the advantage of acquiring patient craniofacial surface images quickly and noninvasively. Before morphometry using digital photogrammetry can be applied in clinical and research practice, it must be assessed against direct anthropometry. Objective: To evaluate the validity and reliability of facial anthropometric linear distances imaged by 3D digital photogrammetry with respect to direct anthropometry. Design, Setting, Participants, Measures: Standard craniofacial distances were directly measured twice on 20 normal adult volunteers. Craniofacial surfaces were also imaged using the 3dMDface digital photogrammetry system, and distances were digitally measured twice for each subject. Validity measures of accuracy and bias (for direct versus digital measurements) and reproducibility measures of precision and test-retest reliability (for repeated sets of digital measurements) were computed. Results: Seventeen of the 18 direct measurements correlated highly with digital values (mean r = 0.88). The correlation for one measurement (upper prolabial width) was not statistically significant. The overall precision of all 17 digital measurements was less than 1 mm, and the reliability was high (mean r = 0.91). Conclusions: Craniofacial anthropometry using the 3dMDface System is valid and reliable. Digital measurements of upper prolabial width may require direct marking, prior to imaging, to improve landmark identification.

The Role of Congenital Muscular Torticollis in the Development of Deformational Plagiocephaly

Background: Numerous risk factors have been associated with the development of deformational plagiocephaly, although the etiology remains unclear. Torticollis and sternocleidomastoid imbalance are implicated, but reporting is variable. The authors sought to determine the incidence of torticollis/sternocleidomastoid imbalance in deformational plagiocephaly. Methods: The authors prospectively evaluated 371 infants with cranial asymmetry between 2002 and 2003. Demographic data and medical history were recorded, and a questionnaire was administered. Cranial asymmetry and head rotation were assessed, and variables were statistically analyzed. Results: Two-hundred two patients were included. Mean age at initial evaluation was 6.1 months (range, 3 to 16 months). Sixty-eight percent (n = 138) were male; 74 percent (n = 149) were flat on the right occiput; 14 percent (n = 28) were from a multiple pregnancy (24 twins, four triplets); 27 percent (n = 54) were premature; and four percent (n = 8) were syndromic. Ninety-three percent (n = 188) of parents did not notice flattening at birth. Ninety-two percent (n = 186) recalled a preferential head position after birth, and in 95 percent of these infants (n = 177 of 186) this improved with age. Only 24 percent (n = 48) of infants had been previously diagnosed or treated for torticollis. Mean cranial asymmetry was 12.5 mm (range, 8 to 25 mm). Ninety-seven percent (n = 195) of infants had head rotational asymmetry of 15 degrees or greater, with more rotation to the flat side. The mean rotational difference was 24 degrees (range 0 to 60; SD 9.8). There was a negative correlation (p = 0.004) between age and head rotational asymmetry (i.e., younger patients exhibited greater asymmetry) and a positive correlation (p = 0.043) between cranial asymmetry and head rotational asymmetry. Conclusions: The incidence of torticollis/sternocleidomastoid imbalance in deformational plagiocephaly is underreported. Because this condition improves rapidly during early infancy, the findings may be subtle and evidenced only by a history of preferential head rotation. The major cause of deformational plagiocephaly is limited head mobility in early infancy secondary to cervical imbalance.

Long-term outcomes of primary craniofacial reconstruction for craniosynostosis: a 12-year experience.

Background: The purpose of this study was to critically assess long-term outcomes after open reconstruction of craniosynostosis within the recent decade. Methods: The authors performed a retrospective, institutional review board–approved review of open repair for craniosynostosis between 1997 and 2009. Surgical factors, complications, and long-term outcomes were assessed. Pearson chi-square, Fishers exact, and Kaplan-Meier analyses were performed. Results: Of 212 patients, 72 underwent primary extended synostectomy and 140 had traditional open craniofacial repair. Mean follow-up was 36.3 months (range, 0.5 to 138 months). Indications included sagittal (n = 96), metopic (n = 40), unicoronal (n = 33), bicoronal (n = 24), multisutural (n = 15), bilambdoidal (n = 3), and unilambdoidal (n = 1) synostoses; 8.5 percent of patients were syndromic. Surgical reconstruction was performed at a mean age of 11.3 months (range, 0.2 to 117.8 months), including nonsyndromic patients at an average age of 10.6 months and syndromic patients at age 19.3 months. There were no deaths. A 3.3 percent complication rate included two cerebral contusions, two hematomas, one cerebrospinal fluid leak, one infection, and one wound breakdown. Patients were categorized as 89.2 percent Whitaker class I/II and 10.8 percent Whitaker class III/IV. Major and total reoperation rates were 9.0 percent and 10.8 percent, respectively. Higher total reoperation rate and Whitaker class III/IV distribution significantly correlated with syndromic diagnosis, bicoronal synostosis, and surgical age younger than 6 months. Conclusions: In this experience of contemporary open craniosynostosis surgery, rates of morbidity, mortality, and reoperation were low. These results support the merits of surgical delay, targeting an age of 6 months or older, and may serve as a more accurate metric of comparison to current minimally invasive techniques for craniosynostosis repair.

Propranolol vs prednisolone for symptomatic proliferating infantile hemangiomas: A randomized clinical trial

IMPORTANCE While propranolol is touted as superior to prednisolone for treating infantile hemangiomas (IH), a randomized clinical trial (RCT) comparing the outcome and tolerability of these medications for symptomatic, proliferating IH has not been reported. OBJECTIVES To determine if oral propranolol is more efficacious and better tolerated than prednisolone in treating symptomatic, proliferating IH and to determine the feasibility of conducting a multi-institutional, RCT comparing efficacy and tolerability of both medications. DESIGN, SETTING, AND PARTICIPANTS Phase 2, investigator-blinded, multi-institutional RCT conducted in 3 academic vascular anomalies clinics on 19 of 44 eligible infants aged between 2 weeks and 6 months. All participating patients had symptomatic proliferating IH treated between September 1, 2010, and August 1, 2012. INTERVENTIONS Treatment with oral propranolol vs prednisolone (2.0 mg/kg/d) until halted owing to toxic effects or clinical response. MAIN OUTCOMES AND MEASURES Primary outcome was change in IH size after 4 months of therapy. Secondary outcomes were response rate and frequency and severity of adverse events (AEs). RESULTS The primary outcome showed no difference in lesion size or affected skin area after 4 months of therapy: 41% and 1.32 mm2 for prednisolone vs 64% and 0.55 mm2 for propranolol (P = .12 for lesion size, and P = .56 for affected skin area). Longitudinal analyses showed a faster response in total lesion outer dimension with prednisolone (P = .03), but this advantage over time was not noted when central clearing and outer dimension were included in the analysis (P = .91). The overall frequency of AEs was similar (44 for prednisolone vs 32 for propranolol) (P = .84), but prednisolone-treated participants had more grade 3 severe AEs (11 vs 1) (P = .01), particularly growth retardation resulting in size and weight below the fifth percentile. Early study withdrawal owing to AEs occurred in 6 (75%) of 8 patients in the prednisolone group but 0 of 11 propranolol-treated participants. The mean duration of therapy was shorter for prednisolone (141 vs 265 days), reflecting the higher rate of early withdrawals. CONCLUSIONS AND RELEVANCE Both medications show similar efficacy for reducing the area of symptomatic, proliferating IH. Although prednisolone showed a faster response rate, propranolol was better tolerated with significantly fewer severe AEs. Propranolol should be the first line of therapy for symptomatic IH unless contraindicated or unless future studies demonstrate severe AEs from propranolol. Recruiting participants for a phase 3 RCT would be difficult owing to safety profiles measured here and emerging trends favoring propranolol. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00967226.

Predictors of severity in deformational plagiocephaly.

Multiple risk factors for deformational plagiocephaly (DP) have been reported. The purpose of this study was to establish the impact of these variables on the severity of this deformity. A prospective cohort study was performed. Parents completed a standardized questionnaire assessing potential risk factors for DP before assessment. Examination included measurement of transcranial difference (TCD; ie, difference in oblique cranial lengths), evaluation of head tilt, and rotational asymmetry. Pearson correlation coefficient, 1-way analysis of variance, and 2-sample t-test were used to quantify the relationship between identified risk factors and TCD. A total of 434 patients with DP were evaluated. Male-to-female ratio was 2:1; mean gestational age was 36.5 weeks. Deformational plagiocephaly was first appreciated at a mean infant age of 6 weeks. A preexisting diagnosis of torticollis was noted in fewer than 50%. Mean TCD was 11.2 mm. Head tilt was documented in 80% of infants, and mean head rotational asymmetry was 16.4 degrees. Deformational plagiocephaly was more severe in multiple birth pregnancies (P < 0.05), males (P < 0.05), infants with a favorite head position (P < 0.01), preexamination diagnosis of torticollis (P < 0.05), and infants with a head tilt (P < 0.05). Lower gestational age (P < 0.05) and greater head rotational asymmetry (P < 0.0001) were found to correlate with DP severity. This study suggests that the relationship between the severity of DP and certain risk factors can be quantified. The presence and degree of cervical imbalance correlate strongly with deformational cranial asymmetry.

Helmet treatment of deformational plagiocephaly: The relationship between age at initiation and rate of correction

Background: The purpose of this study was to evaluate the relationship between age at initiation of helmet therapy for deformational plagiocephaly and the rate of correction. Methods: Infants treated for deformational plagiocephaly with a helmet orthosis between 2009 and 2010 were included. Patients were stratified prospectively by the age at which treatment was initiated: group 1, younger than 20 weeks (n = 26); group 2, 20 to 23.9 weeks (n = 59); group 3, 24 to 27.9 weeks (n = 82); group 4, 28 to 31.9 weeks (n = 62); group 5, 32 to 35.9 weeks (n = 45); group 6, 36 to 40 weeks (n = 29), and group 7, older than 40 weeks (n = 43). Pretreatment and posttreatment calvarial asymmetry was measured using direct anthropometry and reported as a transcranial difference. Results: Three hundred forty-six infants were included; initial transcranial difference was equivalent on all paired-group comparisons. Duration of helmet therapy positively correlated with age at initiation (r = 0.89, p < 0.05). The rate of change in transcranial difference correlated negatively with age at treatment onset (r = –0.88, p < 0.05): group 1, 0.93 mm/week; group 2, 0.64 mm/week; group 3, 0.59 mm/week; group 4, 0.56 mm/week; group 5, 0.41 mm/week; group 6, 0.42 mm/week; and group 7, 0.42 mm/week). At the conclusion of therapy, all groups had improved calvarial symmetry, albeit less completely in groups 6 and 7. Conclusions: The correction rate of plagiocephaly with helmet therapy decreases with increasing infant age; after 32 weeks, there is a slow and relatively constant rate of change. Improvement can still be achieved in infants older than 12 months. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, II.

Further clinical and molecular delineation of the 15q24 microdeletion syndrome

Background Chromosome 15q24 microdeletion syndrome is a rare genomic disorder characterised by intellectual disability, growth retardation, unusual facial morphology and other anomalies. To date, 20 patients have been reported; 18 have had detailed breakpoint analysis. Aim To further delineate the features of the 15q24 microdeletion syndrome, the clinical and molecular characterisation of fifteen patients with deletions in the 15q24 region was performed, nearly doubling the number of reported patients. Methods Breakpoints were characterised using a custom, high-density array comparative hybridisation platform, and detailed phenotype information was collected for each patient. Results Nine distinct deletions with different breakpoints ranging in size from 266 kb to 3.75 Mb were identified. The majority of breakpoints lie within segmental duplication (SD) blocks. Low sequence identity and large intervals of unique sequence between SD blocks likely contribute to the rarity of 15q24 deletions, which occur 8–10 times less frequently than 1q21 or 15q13 microdeletions in our series. Two small, atypical deletions were identified within the region that help delineate the critical region for the core phenotype in the 15q24 microdeletion syndrome. Conclusion The molecular characterisation of these patients suggests that the core cognitive features of the 15q24 microdeletion syndrome, including developmental delays and severe speech problems, are largely due to deletion of genes in a 1.1–Mb critical region. However, genes just distal to the critical region also play an important role in cognition and in the development of characteristic facial features associated with 15q24 deletions. Clearly, deletions in the 15q24 region are variable in size and extent. Knowledge of the breakpoints and size of deletion combined with the natural history and medical problems of our patients provide insights that will inform management guidelines. Based on common phenotypic features, all patients with 15q24 microdeletions should receive a thorough neurodevelopmental evaluation, physical, occupational and speech therapies, and regular audiologic and ophthalmologic screening.

Facial asymmetry in unilateral coronal synostosis: long-term results after fronto-orbital advancement.

Background: Unilateral coronal synostosis causes asymmetry of the forehead and face. The authors set out to document asymmetry and rotation of the middle/lower facial soft tissues using three-dimensional photogrammetry in adolescent and adult patients with unilateral coronal synostosis who underwent correction in infancy. Methods: All patients older than 10 years who had bilateral fronto-orbital advancement in infancy for nonsyndromic unilateral coronal synostosis were eligible for this study. The following paired anthropometric distances were measured: medial canthus to facial midline distance (endocanthion to sellion); middle facial depth (tragion to subnasale); and lower facial depth (tragion to gnathion). Nasal tip deviation (sellion to pronasale) and facial midline deviation (sellion to subnasale to gnathion) were also measured. Results: There were 15 patients with an average age at fronto-orbital advancement of 8 months (range, 3 to 14 months). Three-dimensional digital images were taken at an average age of 14 years (range, 11 to 29 years). Digital anthropometry documented decreased mean middle facial depth (5.1 ± 3.2 mm; p < 0.00001) and lower facial depth (2.7 ± 2.5 mm; p < 0.00001) on the fused side. Average deviation of the nasal tip and facial midline to the nonfused side was 5.0 ± 1.2 degrees and 3.4 ± 0.7 degrees, respectively. All 15 patients exhibited rotation of the middle and lower face to the nonfused side (chi-square analysis, p < 0.0001). Applying the Bonferroni correction, asymmetry did not correlate with age at frontal advancement or age at digital imaging. Conclusion: Adolescents and adults with unilateral coronal synostosis who underwent fronto-orbital advancement in infancy have consistent middle and lower facial asymmetry.

Unreliability of intraoperative estimated blood loss in extended sagittal synostectomies

OBJECT Intraoperative blood loss represents a significant concern during open repair of craniosynostosis, and its reliable measurement remains a serious challenge. In this study of extended sagittal synostectomies, the authors analyzed the relationship between estimated blood loss (EBL) and calculated blood loss (CBL), and investigated predictors of hemodynamic outcomes. METHODS The authors reviewed outcomes in infants with sagittal synostosis who underwent primary extended synostectomies (the so-called Pi procedure) between 1997 and 2009. Patient demographic data, operating time, and mean arterial pressures (MAPs) were recorded. Serial MAPs were averaged for a MAP(mean). The EBL was based on anesthesia records, and the CBL on pre- and postoperative hemoglobin values in concert with transfusion volumes. Factors associated with EBL, CBL, red blood cell transfusion (RBCT), and hospital length of stay (LOS) were investigated. Hemodynamic outcomes were reported as percent estimated blood volume (% EBV), and relationships were analyzed using simple and multiple linear and logistic regression models. A p value < 0.05 was considered significant. RESULTS Seventy-one infants with sagittal synostosis underwent primary extended synostectomies at a mean age and weight of 4.9 months and 7.3 kg, respectively. The average operating time was 1.4 hours, and intraoperative MAP was 54.6 mm Hg (21.3% lower than preoperative baseline). There was no association between mean EBL (12.7% EBV) and mean CBL (23.6% EBV) (r = 0.059, p = 0.63). The EBL inversely correlated with the patients age (r = -0.07) and weight (r = -0.11) at surgery (p < 0.05 in both instances). With regard to intraoperative factors, EBL positively trended with operating time (r = 0.26, p = 0.09) and CBL inversely trended with MAP(mean) (r = -0.04, p = 0.10), although these relationships were only borderline significant. Intraoperative RBCT, which was required in 59.1% of patients, positively correlated with EBL (r = 1.55, p < 0.001), yet negatively trended with CBL (r = -0.40, p = 0.01). Undertransfusion was significantly more common than overtransfusion (40.8% vs 22.5%, p = 0.02, respectively). The mean hospital LOS was 2.3 days and was not significantly associated with patient demographic characteristics, intraoperative factors, blood loss, RBCT, or total fluid requirements. CONCLUSIONS In extended synostectomies for sagittal synostosis, EBL and CBL demonstrated a decided lack of correlation with one another. Intraoperative blood transfusion positively correlated with EBL, but inversely correlated with CBL, with a significantly higher proportion of patients undertransfused than overtransfused. These findings highlight the need for reliable, real-time monitoring of intraoperative blood loss to provide improved guidance for blood and fluid resuscitation.

Clinical correlation of chromosome 22q11.2 fluorescent in situ hybridization analysis and velocardiofacial syndrome.

Objective: To identify characteristics associated with microdeletions of chromosome 22q11.2 ascertained by fluorescent in situ hybridization (FISH) analysis in patients with velopharyngeal insufficiency (VPI), cleft palate, or other clinical features of velocardiofacial syndrome (VCFS). Design/Setting: Retrospective review of all patients entered at one tertiary-level multidisciplinary cleft lip and palate and craniofacial anomalies panel from January 2000 to December 2003. Patients: The study consisted of 115 patients. The presence or absence of the following clinical features was documented: cleft palate (submucous and overt), VPI, cardiac anomalies, renal anomalies, small stature, characteristic facies, developmental delay, psychiatric dysfunction, and family history. Main Outcome Measure: Correlation between presence or absence of clinical features of VCFS and presence or absence of 22q11.2 microdeletion by FISH analysis. Results: Of the 16 patients (13.9%) who demonstrated 22q11.2 microdeletion by FISH analysis, 16 had VPI (100%), 16 had small stature (100%), 14 had cleft palate (88%), and 13 had characteristic facies (81%). Developmental delay was also present in 13 of these patients (81%), and seven had cardiac anomalies (44%). Multiple regression analysis revealed that the presence of characteristic facies and small stature statistically correlated with microdeletions of chromosome 22q11.2 by FISH studies (p < .05). Conclusions: Patients with microdeletions of chromosome 22q11.2 as demonstrated by FISH analysis were more likely to have VPI, small stature, cleft palate, characteristic facies, and developmental delay, in descending order. Statistical analysis showed that only characteristic facies and small stature correlated with 22q11.2 microdeletions.