Overlapping Spectrum of Craniofacial Microsomia Phenotype in Cat-Eye Syndrome.

This study reports three patients with Cat-eye Syndrome (CES), two of which present a previous clinical diagnosis of Craniofacial microsomia (CFM). Chromosomal microarray analysis (CMA) revealed a tetrasomy of 1,7 Mb at the 22q11.2q11.21 region, which is the typical region triplicated in the CES, in all patients. The most frequent craniofacial features found in individuals with CFM and CES are preauricular tags and/or pits and mandibular hypoplasia. We reinforce that the candidate genes for CFM features, particularly ear malformation, preauricular tags/pits, and facial asymmetry, can be in the proximal region of the 22q11.2 region.

Genetic Testing to Inform Epilepsy Treatment Management From an International Study of Clinical Practice.

Importance: It is currently unknown how often and in which ways a genetic diagnosis given to a patient with epilepsy is associated with clinical management and outcomes. Objective: To evaluate how genetic diagnoses in patients with epilepsy are associated with clinical management and outcomes. Design, Setting, and Participants: This was a retrospective cross-sectional study of patients referred for multigene panel testing between March 18, 2016, and August 3, 2020, with outcomes reported between May and November 2020. The study setting included a commercial genetic testing laboratory and multicenter clinical practices. Patients with epilepsy, regardless of sociodemographic features, who received a pathogenic/likely pathogenic (P/LP) variant were included in the study. Case report forms were completed by all health care professionals. Exposures: Genetic test results. Main Outcomes and Measures: Clinical management changes after a genetic diagnosis (ie, 1 P/LP variant in autosomal dominant and X-linked diseases; 2 P/LP variants in autosomal recessive diseases) and subsequent patient outcomes as reported by health care professionals on case report forms. Results: Among 418 patients, median (IQR) age at the time of testing was 4 (1-10) years, with an age range of 0 to 52 years, and 53.8% (n = 225) were female individuals. The mean (SD) time from a genetic test order to case report form completion was 595 (368) days (range, 27-1673 days). A genetic diagnosis was associated with changes in clinical management for 208 patients (49.8%) and usually (81.7% of the time) within 3 months of receiving the result. The most common clinical management changes were the addition of a new medication (78 [21.7%]), the initiation of medication (51 [14.2%]), the referral of a patient to a specialist (48 [13.4%]), vigilance for subclinical or extraneurological disease features (46 [12.8%]), and the cessation of a medication (42 [11.7%]). Among 167 patients with follow-up clinical information available (mean [SD] time, 584 [365] days), 125 (74.9%) reported positive outcomes, 108 (64.7%) reported reduction or elimination of seizures, 37 (22.2%) had decreases in the severity of other clinical signs, and 11 (6.6%) had reduced medication adverse effects. A few patients reported worsening of outcomes, including a decline in their condition (20 [12.0%]), increased seizure frequency (6 [3.6%]), and adverse medication effects (3 [1.8%]). No clinical management changes were reported for 178 patients (42.6%). Conclusions and Relevance: Results of this cross-sectional study suggest that genetic testing of individuals with epilepsy may be materially associated with clinical decision-making and improved patient outcomes.

Identification of genomic imbalances in oral clefts

Abstract Objective This article presents a clinical and cytogenomic approach that focuses on the diagnosis of syndromic oral clefts (OCs). Methods The inclusion criteria were individuals with OC presenting four or more minor signs and no major defects (non-syndromic oral clefts [NSOCs]) as well as individuals with OC presenting at least another major defect, regardless of the number of minor signs (syndromic oral clefts [SOCs]). The exclusion criteria included NSOC with less than four minor signs, SOC with known etiology, as well as atypical oral clefts. Results Of 1647 individuals with OC recorded in the Brazilian Database of Craniofacial Anomalies, 100 individuals were selected for chromosome microarray analysis (CMA). Among these, 44 individuals were clinically classified as NSOC and 56 as SOC. CMA was performed for both groups, and abnormal CMA was identified in 9%, all previously classified as SCO. The clinical and CMA data analyses showed a significant predominance of abnormal CMA in individuals classified as SOC (p = 0.0044); prematurity, weight, length, and head circumference at birth were significantly lower in the group with abnormal CMA. Besides, minor signs were significantly higher in this group (p = 0.0090). Conclusion The rigorous selection of cases indicates that the significant variables could help in early recognition of SOC. This study reinforces the importance of applying the CMA technique to establish the diagnosis of SOC. This is an important and universal issue in clinical practice for intervention, care, and genetic counseling.

Identification of genomic imbalances in oral clefts.

OBJECTIVE: This article presents a clinical and cytogenomic approach that focuses on the diagnosis of syndromic oral clefts (OCs). METHODS: The inclusion criteria were individuals with OC presenting four or more minor signs and no major defects (non-syndromic oral clefts [NSOCs]) as well as individuals with OC presenting at least another major defect, regardless of the number of minor signs (syndromic oral clefts [SOCs]). The exclusion criteria included NSOC with less than four minor signs, SOC with known etiology, as well as atypical oral clefts. RESULTS: Of 1647 individuals with OC recorded in the Brazilian Database of Craniofacial Anomalies, 100 individuals were selected for chromosome microarray analysis (CMA). Among these, 44 individuals were clinically classified as NSOC and 56 as SOC. CMA was performed for both groups, and abnormal CMA was identified in 9%, all previously classified as SCO. The clinical and CMA data analyses showed a significant predominance of abnormal CMA in individuals classified as SOC (p = 0.0044); prematurity, weight, length, and head circumference at birth were significantly lower in the group with abnormal CMA. Besides, minor signs were significantly higher in this group (p = 0.0090). CONCLUSION: The rigorous selection of cases indicates that the significant variables could help in early recognition of SOC. This study reinforces the importance of applying the CMA technique to establish the diagnosis of SOC. This is an important and universal issue in clinical practice for intervention, care, and genetic counseling.

Genomic imbalances in craniofacial microsomia.

The aim of this study was to perform 22q11.2 deletion screening and chromosomal microarray analysis (CMA) in individuals clinically diagnosed with craniofacial microsomia (CFM) and review previously published cases of CFM with genomic imbalances. It included 54 individuals who were evaluated by a clinical geneticist. Copy number variants (CNVs) in the 22q11.2 region were investigated by multiplex ligation-dependent probe amplification (MLPA) for all individuals. The CMA was performed only for individuals with additional major features. MLPA revealed pathogenic CNVs at the 22q11 region in 3/54 (5.6%) individuals. CMA revealed pathogenic CNVs in 4/17 (23.5%) individuals, including the three CNVs at the 22q11 region also detected by MLPA, and CNVs classified as variants of unknown significance (VOUS) in 4/17 (23.5%) individuals. Pathogenic alterations were found at the 2p12, 5p15, 13q13, and 22q11 regions. VOUS were found at 3q29, 5q22.2, 5q22.1, and 9p22 regions. All individuals with pathogenic alterations presented additional major features, including congenital heart disease (CHD). The literature review revealed pathogenic CNVs in 17/193 (8.8%) individuals and most of them also presented additional major features, such as CHD, renal anomalies, or developmental delay. In conclusion, CNVs should be investigated in patients with CFM and additional major features.

Echocardiographic study in children with osteogenesis imperfecta.

BACKGROUND: Osteogenesis imperfecta is a collagen type I bone disorder. Recently, extra-skeletal manifestations have been described, including many cardiovascular alterations. This study aims to report echocardiogram study in children with osteogenesis imperfecta compared to a control group. METHODS: A cross-sectional comparative study took place in the Reference Center for Treatment of Osteogenesis Imperfecta in Southern Brazil. Fifty-four patients with osteogenesis imperfecta were paired with 54 controls, based on body surface area, and echocardiogram findings were compared. RESULTS: All cases were asymptomatic for cardiac manifestations. The case group presented significant larger values in aortic diameter, left atrium diameter, left ventricule end-diastolic diameter, left ventricule end-systolic diameter, and right ventricle diameter compared with the control group. The analysis considering the severity of osteogenesis imperfecta shows that in mild osteogenesis imperfecta, the aortic diameter (p < 0.001), left atrium diameter (p = 0.002), left ventricule end-diastolic diameter (p = 0.001), left ventricule end-systolic diameter (p = 0.026), and right ventricle diameter (p < 0.001) were significantly larger than in the control group. Patients with moderate/severe osteogenesis imperfecta had similar results, with aortic diameter (p < 0.001), left atrium diameter (p < 0.001), left ventricule end-diastolic diameter (p = 0.013), and left ventricule end-systolic diameter (0.004) statistically larger than controls. Twenty-six (48.1%) of the cases had physiological tricuspid regurgitation and in controls this finding was observed in eight (14.8%) (p < 0.001). CONCLUSION: Children with osteogenesis imperfecta presented cardiac function within the normal pattern, but dimensions of left ventricular dimensions were increased compared to the ones of the controls.

Identification of Novel and Recurrent RMRP Variants in a Series of Brazilian Patients with Cartilage-Hair Hypoplasia: McKusick Syndrome.

Cartilage-hair hypoplasia syndrome (CHH) is an autosomal recessive disorder caused by pathogenic variants of the RMRP gene and characterized by metaphyseal bone dysplasia associated with hypotrichosis, immunodeficiency, and predisposition to malignancy. However, the genotype-phenotype correlation in CHH is not well understood. Here, we report a single country cohort of 23 Brazilian patients with clinical and radiological features consistent with CHH. We found 23 different pathogenic variants in the RMRP gene - 12 novel and 11 previously described in the literature. Interestingly, the most frequent Finnish pathogenic variant related to CHH (g.71A>G) was not found in our cohort. In contrast, more than 50% of the patients carried the rare g.196C>T variant suggesting a possible founder effect in the Brazilian population. In silico analysis showed that pathogenic variants occurred either in the regions conserved in mammalian species or within essential domains for the ribonucleoprotein complex. Pathogenicity prediction studies can improve the understanding of how these variants affect RNA.

Collagen I Defect Corneal Profiles in Osteogenesis Imperfecta.

PURPOSE: The goal of this study was to evaluate corneal profiles of patients with osteogenesis imperfecta (OI) due to a collagen I gene mutation. METHODS: This was a cross-sectional comparative study. There were 84 eyes from 42 patients with OI types I, III, and IV who were recruited from the OI Clinic at the Clinical Hospital of Porto Alegre, Brazil. All cases presented either COL1A1 or A2 gene mutations. Controls were matched by sex, age, and refractive error. Corneal Scheimpflug tomography was used to determine curvature and thickness parameters in both groups. RESULTS: Quantitative collagen mutations were found only in OI type I. Qualitative mutations were responsible for all mutations observed in type III and IV patients. Each OI type presented significantly lower pachymetric values at the thinnest point compared with controls (443.7-505.1 vs. 541.9-548.5 µm; P < 0.001). In addition, significantly lower pachymetric values were observed in patients with OI compared with controls in all positions between the central and corneal periphery (581.4-657.0 vs. 704.5-720.7 µm at an 8.0-mm-diameter circle; P < 0.001). Differences in anterior and posterior radii of curvatures, respectively, between patients with OI and controls were not statistically significant (7.64-7.80 vs. 7.65-7.69 mm; P > 0.05) except for a lower anterior radii of curvatures in type III (7.33 vs. 7.72 mm; P < 0.01). CONCLUSIONS: Although patients with OI have homogenously thinner corneas compared with controls, we observed that a collagen I chain mutation was not responsible for corneal curvature alterations in OI.

CranFlow: An Application for Record-Taking and Management Through the Brazilian Database on Craniofacial Anomalies.

BACKGROUND: The World Health Organization has recognized the relevance of databases on craniofacial anomalies since . To date, there is no universal standard instrument/database focused on risk factors, clinical and genetic data collection, and follow-up that enables comparison between different populations and genotype-phenotype correlation. Although studies have shown that specific genes would impact outcomes, knowledge is not sufficient to subsidize cost-effectiveness strategies for diagnosis, surgical decision, and a multi-professional approach toward personalized medicine. METHODS: Based on a clinical genetic approach, a Web-based application named CranFlow-Craniofacial Anomalies: Registration, Flow, and Management has been developed. It prospectively collects clinical and genetic information for the Brazilian Database on Craniofacial Anomalies (syndromic and nonsyndromic orofacial cleft, 22q11.2 deletion syndrome, and other craniofacial related disorders). A comprehensive list of CranFlow's features is provided. RESULTS: We present preliminary results on 1546 cases already recorded and followed, which allows recognizing 10% of diagnosis changes. CONCLUSION: The identification of risk factors, consistent genetic approach associated with clinical data and follow-up result in valuable information to develop and improve personalized treatment and studies on genotype-phenotype correlation. Adoption of CranFlow in different clinical services may support comparison between populations. This application has the potential to contribute to improvements in healthcare, quality of services, clinical and surgical outcomes, and the standard of living of individuals with craniofacial anomalies. Birth Defects Research 110:72-80, 2018. © 2017 Wiley Periodicals, Inc.

Difference between Methods for Estimation of Basal Metabolic Rate and Body Composition in Pediatric Patients with Osteogenesis Imperfecta.

BACKGROUND/AIMS: Osteogenesis Imperfecta (OI) is a bone disease characterized by bone fragility, deformities, and multiple fractures. The aim of this study was to compare the different methods of measuring the basal metabolic rate (BMR) and body composition (BC) in pediatric patients with OI. METHODS: This cross-sectional study included 52 individuals with a median age of 9 (5.25-12.7) years. BMR was calculated by bioelectrical impedance analyses (BIA), predictive values according to age from the World Health Organization (WHO), a kcal/cm formula, and indirect calorimetry (IC). BC was assessed using the anthropometric calculation of percentage body fat (%BF) and lean mass (kg), BIA, and dual-energy X-ray absorptiometry (DEXA). Agreement among the methods was assessed using the Bland-Altman technique. RESULTS: IC estimates of BMR were greater than BIA and lower than values obtained using the WHO and kcal/cm methods. Better agreement was observed using the WHO values for mild forms of OI and the kcal/cm formula for moderate-to-severe forms. For BC, DEXA estimates of %BF were higher and the lean mass was lower than the values obtained using BIA and anthropometry. Neither method agreed with the DEXA method results. CONCLUSIONS: Significant differences exist among the various methods used for measuring BMR and BC with regard to phenotypic differences between OI types.

Correction: Biotinidase deficiency: Genotype-biochemical phenotype association in Brazilian patients.

[This corrects the article DOI: 10.1371/journal.pone.0177503.].

Biotinidase deficiency: Genotype-biochemical phenotype association in Brazilian patients.

INTRODUCTION: The association between the BTD genotype and biochemical phenotype [profound biotinidase deficiency (BD), partial BD or heterozygous activity] is not always consistent. This study aimed to investigate the genotype-biochemical phenotype association in patients with low biotinidase activity. METHODS: All exons, the 5'UTR and the promoter of the BTD gene were sequenced in 72 Brazilian individuals who exhibited low biotinidase activity. For each patient, the expected biochemical phenotype based on the known genotype was compared with the observed biochemical phenotype. Additional non-genetic factors that could affect the biotinidase activity were also analysed. RESULTS: Most individuals were identified by neonatal screening (n = 66/72). When consecutive results for the same patient were compared, age, prematurity and neonatal jaundice appeared to affect the level of biotinidase activity. The biochemical phenotype at the time of the second blood collection changed in 11/22 patients compared to results from the first sample. Three novel variants were found: c.1337T>C (p.L446P), c.1466A>G (p.N489S) and c.962G>A (p.W321*). Some patients with the same genotype presented different biochemical phenotypes. The expected and observed biochemical phenotypes agreed in 68.5% of cases (concordant patients). The non-coding variants c.-183G>A, c.-315A>G and c.-514C>T were present in heterozygosis in 5/17 discordant patients. In addition, c.-183G>A and c.-514C>T were also present in 10/37 concordant patients. CONCLUSIONS: The variants found in the promoter region do not appear to have a strong impact on biotinidase activity. Since there is a disparity between the BTD genotype and biochemical phenotype, and biotinidase activity may be affected by both genetic and non-genetic factors, we suggest that the diagnosis of BD should be based on more than one measurement of plasma biotinidase activity. DNA analysis can be of additional relevance to differentiate between partial BD and heterozygosity.

Targeted Resequencing of Deafness Genes Reveals a Founder MYO15A Variant in Northeastern Brazil.

Identifying the genetic etiology in a person with hearing loss (HL) is challenging due to the extreme genetic heterogeneity in HL and the population-specific variability. In this study, after excluding GJB2 variants, targeted resequencing of 180 deafness-related genes revealed the causative variants in 11 of 19 (58%) Brazilian probands with autosomal recessive HL. Identified pathogenic variants were in MYO15A (10 families) and CLDN14 (one family). Remarkably, the MYO15A p.(Val1400Met) variant was identified in eight families from the city of Monte Santo in the northeast region of Brazil. Haplotype analysis of this variant was consistent with a single founder. No other cases with this variant were detected among 105 simplex cases from other cities of northeastern Brazil, suggesting that this variant is confined to a geographical region. This study suggests that it is feasible to develop population-specific screening for deafness variants once causative variants are identified in different geographical groups.

Intellectual Disability in a Birth Cohort: Prevalence, Etiology, and Determinants at the Age of 4 Years.

BACKGROUND: Intellectual disability (ID), characterized by impairments in intellectual function and adaptive behavior, affects 1-3% of the population. Many studies investigated its etiology, but few are cohort studies in middle-income countries. AIMS: To estimate prevalence, etiology, and factors related to ID among children prospectively followed since birth in a Southern Brazilian city (Pelotas). METHODS: In 2004, maternity hospitals were visited daily and births were identified. Live-born infants (n = 4,231) whose family lived in the urban area have been followed for several years. At the age of 2 and 4 years, performances in development and intelligence tests were evaluated using the Battelle Developmental Inventory and Wechsler Intelligence Scale, respectively. Children considered as having developmental delay were invited to attend a genetic evaluation. RESULTS: At 4 years of age, the prevalence of ID was 4.5%, and the etiology was classified into 5 groups: environmental (44.4%), genetic (20.5%), idiopathic (12.6%), neonatal sequelae (13.2%), other diseases (9.3%). Most children presented impairment in two or more areas of adaptive behavior. There was no difference in prenatal care attendance or maternal schooling among the groups. CONCLUSION: For about 40% of children, ID was attributed to nonbiological factors, suggesting that the rate may be reduced with appropriate interventions early in life.

TBC1D24 genotype-phenotype correlation: Epilepsies and other neurologic features.

OBJECTIVE: To evaluate the phenotypic spectrum associated with mutations in TBC1D24. METHODS: We acquired new clinical, EEG, and neuroimaging data of 11 previously unreported and 37 published patients. TBC1D24 mutations, identified through various sequencing methods, can be found online (http://lovd.nl/TBC1D24). RESULTS: Forty-eight patients were included (28 men, 20 women, average age 21 years) from 30 independent families. Eighteen patients (38%) had myoclonic epilepsies. The other patients carried diagnoses of focal (25%), multifocal (2%), generalized (4%), and unclassified epilepsy (6%), and early-onset epileptic encephalopathy (25%). Most patients had drug-resistant epilepsy. We detail EEG, neuroimaging, developmental, and cognitive features, treatment responsiveness, and physical examination. In silico evaluation revealed 7 different highly conserved motifs, with the most common pathogenic mutation located in the first. Neuronal outgrowth assays showed that some TBC1D24 mutations, associated with the most severe TBC1D24-associated disorders, are not necessarily the most disruptive to this gene function. CONCLUSIONS: TBC1D24-related epilepsy syndromes show marked phenotypic pleiotropy, with multisystem involvement and severity spectrum ranging from isolated deafness (not studied here), benign myoclonic epilepsy restricted to childhood with complete seizure control and normal intellect, to early-onset epileptic encephalopathy with severe developmental delay and early death. There is no distinct correlation with mutation type or location yet, but patterns are emerging. Given the phenotypic breadth observed, TBC1D24 mutation screening is indicated in a wide variety of epilepsies. A TBC1D24 consortium was formed to develop further research on this gene and its associated phenotypes.

Clinical and Molecular Characterization of Osteogenesis Imperfecta Type V.

Osteogenesis imperfecta type V (OI-V) has a wide clinical variability, with distinct clinical/radiological features, such as calcification of the interosseous membrane (CIM) between the radius-ulna and/or tibia-fibula, hyperplastic callus (HPC) formation, dislocation of the radial head (DRH), and absence of dentinogenesis imperfecta (DI). Recently, a single heterozygous mutation (c.-14C>T) in the 5'UTR of the IFITM5 gene was identified to be causative for OI-V. Here, we describe 7 individuals from 5 unrelated families that carry the c.-14C>T IFITM5 mutation. The clinical findings in these cases are: absence of DI in all patients, presence of blue sclera in 2 cases, and 4 patients with DRH. Radiographic findings revealed HPC in 3 cases. All patients presented CIM between the radius and ulna, while 4 patients presented additional CIM between the tibia and fibula. Spinal fractures by vertebral compression were observed in all individuals. The proportion of cases identified with this mutation represents 4% of OI cases at our institution. The clinical identification of OI-V is crucial, as this mutation has an autosomal dominant inheritance with variable expressivity.

Quality of life in caregivers of children and adolescents with Osteogenesis Imperfecta.

BACKGROUND: Osteogenesis imperfecta (OI) is a group of genetic disorders of collagen biosynthesis, characterized by low bone density leading to fractures. Most patients exhibit functional impairment and require the aid of a caregiver. The aim of this study is to assess the quality of life (QoL) of caregivers of patients with OI. METHODS: In this cross-sectional study, a convenience sampling strategy was used to enroll adult caregivers of children and adolescents with OI who attended a referral center in southern Brazil. The WHOQOL-BREF instrument was used to assess QoL. RESULTS: Twenty-four caregivers of 27 patients (10 with type I, 4 with type III, and 13 with type IV OI) were included in the study. Eighteen caregivers were the patients' mothers, two had OI, and 22 cared for only one patient. Mean WHOQOL-BREF scores were 14.59 for the physical health domain, 13.80 for the psychological domain, 15.19 for the social relationships domain, and 12.87 for the environmental domain; the mean total QoL score was 14.16. QoL scores did not differ significantly according to patients' OI type or number of fractures. Economic status was not correlated significantly with QoL scores. CONCLUSIONS: QoL appears to be impaired in caregivers of patients with OI. Additional studies are required to confirm these findings and to ascertain which factors account for this phenomenon.

Genetic causes of intellectual disability in a birth cohort: a population-based study.

Intellectual disability affects approximately 1-3% of the population and can be caused by genetic and environmental factors. Although many studies have investigated the etiology of intellectual disability in different populations, few studies have been performed in middle-income countries. The present study estimated the prevalence of genetic causes related to intellectual disability in a cohort of children from a city in south Brazil who were followed from birth. Children who showed poor performance in development and intelligence tests at the ages of 2 and 4 were included. Out of 4,231 liveborns enrolled in the cohort, 214 children fulfilled the inclusion criteria. A diagnosis was established in approximately 90% of the children evaluated. Genetic causes were determined in 31 of the children and 19 cases remained unexplained even after extensive investigation. The overall prevalence of intellectual disability in this cohort due to genetic causes was 0.82%. Because this study was nested in a cohort, there were a large number of variables related to early childhood and the likelihood of information bias was minimized by collecting information with a short recall time. This study was not influenced by selection bias, allowing identification of intellectual disability and estimation of the prevalence of genetic causes in this population, thereby increasing the possibility of providing appropriate management and/or genetic counseling.

Clinical Features in Patients With 22q11.2 Deletion Syndrome Ascertained by Palatal Abnormalities.

OBJECTIVES: The aim of this study was to describe clinical features in subjects with palatal abnormalities and to assess the distribution of these features among those with and without 22q11.2 deletion. DESIGN: Descriptive cohort. PATIENTS: One hundred patients with palatal abnormalities and suspicion of 22q11.2 DS were included. METHODS: All patients were evaluated by a clinical geneticist, who completed a standardized clinical protocol. The 22q11.2 deletion screening was performed with fluorescence in situ hybridization using the TUPLE1 probe and multiplex ligation-dependent probe amplification using the P250-A1 kit. RESULTS: The 22q11.2 deletion was detected in 35 patients, in whom the most frequent clinical features were congenital heart disease (15/30 - 50%), developmental delay (19/35 - 54%), speech delay (20/35 - 57%), learning disabilities (27/35 - 77%), immunologic alterations (18/29 - 62%). In addition, the most common facial dysmorphisms in this group were long face (27/35 - 77%), typical nose (24/35 - 69%), and hooded eyelids (19/35 - 54%). Comparing features in patients with or without the deletion revealed significant differences (positively correlated with the deletion) for speech delay, learning disabilities, conductive hearing loss, number of dysmorphisms, long face, and hooded eyelids. Cleft lip and palate was negatively correlated with the deletion. CONCLUSIONS: The presence of speech delay, learning disabilities, conductive hearing loss, long face, and hooded eyelids should reinforce the suspicion of 22q11.2 DS in patients with palatal abnormalities and would help professionals direct clinical follow-up of these patients.

Anthropometry, nutritional status, and dietary intake in pediatric patients with osteogenesis imperfecta.

OBJECTIVE: The aim of the present study was to assess anthropometric measurements, nutritional status, dietary intake, and body fat percentage of pediatric patients with osteogenesis imperfecta (OI). METHOD: A cross-sectional study evaluated 63 OI patients from 0 to 19 years of age. We analyzed anthropometric measurements, mobility, bisphosphonate treatment, body fat percentage (by dual-energy x-ray absorptiometry [DEXA] and sum of skinfold thickness), nutritional status, and dietary intake (using World Health Organization [WHO] and dietary reference intake recommendations for macronutrients and calcium intake, respectively). Participants' energy requirements were calculated using both kilocalorie per centimeter measurements and WHO methods. RESULTS: Patients with different types of OI had different anthropometric measurements (p < 0.05), where OI type III had severely limited stature and poor mobility. Nutritional status was correlated with measurements of arm circumference and body fat. We also found a strong correlation between the 2 methods used to calculate percentage of body fat (r = 0.803). OI type III had a higher percentage of energy intake. We observed that 75% of subjects had a calcium intake below 95% of recommended daily value and there was an inverse correlation between age and calcium intake. CONCLUSIONS: This study showed that stature was compromised mainly in OI type III. Skinfold thickness and arm circumference correlated to nutritional status and also to body fat calculated by DEXA. Daily calcium intake was below the recommended levels in pediatric patients with OI. These findings are important for the management of OI subjects.