Disease progression in Sanfilippo type B: Case series of Brazilian patients.

Mucopolysaccharidosis type IIIB (MPS IIIB) is caused by deficiency of alpha-N-acetylglucosaminidase, leading to storage of heparan sulphate. The disease is characterized by intellectual disability and hyperactivity, among other neurological and somatic features. Here we studied retrospective data from a total of 19 MPS IIIB patients from Brazil, aiming to evaluate disease progression. Mean age at diagnosis was 7.2 years. Speech delay was one of the first symptoms to be identified, around 2-3 years of age. Behavioral alterations include hyperactivity and aggressiveness, starting around age four. By the end of the first decade, patients lost acquired abilities such as speech and ability to walk. Furthermore, as disease progresses, respiratory, cardiovascular and joint abnormalities were found in more than 50% of the patients, along with organomegaly. Most common cause of death was respiratory problems. The disease progression was characterized in multiple systems, and hopefully these data will help the design of appropriate clinical trials and clinical management guidelines.

Photoanthropometric craniofacial parameters in individuals with osteogenesis imperfecta / Parámetros craneofaciales fotoantropométricos en personas con osteogénesis imperfecta

Background: This study aimed to evaluate facial photoanthropometric parameters in patients with OI.Material and Methods: We selected 20 Brazilian patients diagnosed with OI treated at the Extension Service forMinors in Need of Specialized Treatment of the Dentistry Course at the Federal University of Ceará (Fortaleza,Brazil), of both sexes, without age restriction, and able to understand and sign the informed consent form (ICF).As a control group, 38 non-syndromic Brazilian individuals, categorized as ASA I, able to understand and sign theICF, matched by sex, age, and Legan and Burstone facial profile were selected. The exclusion criteria were: previ-ous orthodontic treatment, craniofacial trauma and/or surgery, and the presence of any other systemic diseases.Photoanthropometric analysis of the 18 facial parameters proposed by Stengel-Rutkowski et al. (1984), previouslyestablished in the literature for craniofacial syndromes, were conducted. A single examiner digitally performedall effective and angular measurements with the CorelDRAWX7® software.Results: Horizontally shortened ears (p<0.001) but larger in height in relation to the face (p=0.012) were shownto be alterations belonging to individuals with OI.Conclusions: OI patients present distinct photoanthropometric parameters inherent in this condition.(AU)

Higher Prevalence of Nonsense Pathogenic DMD Variants in a Single-Center Cohort from Brazil: A Genetic Profile Study That May Guide the Choice of Disease-Modifying Treatments.

Dystrophinopathies are muscle diseases caused by pathogenic variants in DMD, the largest gene described in humans, representing a spectrum of diseases ranging from asymptomatic creatine phosphokinase elevation to severe Duchenne muscular dystrophy (DMD). Several therapeutic strategies are currently in use or under development, each targeting different pathogenic variants. However, little is known about the genetic profiles of northeast Brazilian patients with dystrophinopathies. We describe the spectrum of pathogenic DMD variants in a single center in northeast Brazil. This is an observational, cross-sectional study carried out through molecular-genetic analysis of male patients diagnosed with dystrophinopathies using Multiplex Ligation-dependent Probe Amplification (MLPA) followed by Next-Generation Sequencing (NGS)-based strategies. A total of 94 male patients were evaluated. Deletions (43.6%) and duplications (10.6%) were the most recurring patterns of pathogenic variants. However, small variants were present in 47.1% of patients, most of them nonsense variants (27.6%). This is the largest South American single-center case series of dystrophinopathies to date. We found a higher frequency of treatment-amenable nonsense single-nucleotide variants than most previous studies. These findings may have implications for diagnostic strategies in less-known populations, as a higher frequency of nonsense variants may mean a higher possibility of treating patients with disease-modifying drugs.

Molecular investigation in individuals with orofacial clefts and microphthalmia-anophthalmia-coloboma spectrum.

This study describes genomic findings among individuals with both orofacial clefts (OC) and microphthalmia/anophthalmia/coloboma (MAC) recorded in the Brazilian Database on Craniofacial Anomalies (BDCA). Chromosomal microarray analysis (CMA) and Whole Exome Sequencing (WES) were performed in 17 individuals with OC-MAC. Clinical interpretation of molecular findings was based on data available at the BDCA and on re-examination. No copy number variants (CNVs) classified as likely pathogenic or pathogenic were detected by CMA. WES allowed a conclusive diagnosis in six individuals (35.29%), two of them with variants in the CHD7 gene, and the others with variants in the TFAP2A, POMT1, PTPN11, and TP63 genes with the following syndromes: CHARGE, CHD7-spectrum, Branchiooculofacial, POMT1-spectrum, LEOPARD, and ADULT. Variants of uncertain significance (VUS) possibly associated to the phenotypes were found in six other individuals. Among the individuals with VUSes, three individuals presented variants in genes associated to defects of cilia structure and/or function, including DYNC2H1, KIAA0586, WDR34, INTU, RPGRIP1L, KIF7, and LMNA. These results show that WES was the most effective molecular approach for OC-MAC in this cohort. This study also reinforces the genetic heterogeneity of OC-MAC, and the importance of genes related to ciliopathies in this phenotype.

Bailey-Bloch Congenital Myopathy in Brazilian Patients: A Very Rare Myopathy with Malignant Hyperthermia Susceptibility.

BACKGROUND: Congenital myopathy-13 (CMYP13), also known as Bailey-Bloch congenital myopathy and Native American myopathy (NAM), is a condition caused by biallelic missense pathogenic variants in STAC3, which encodes an important protein necessary for the excitation-relaxation coupling machinery in the muscle. Patients with biallelic pathogenic variants in STAC3 often present with congenital weakness and arthrogryposis, cleft palate, ptosis, myopathic facies, short stature, kyphoscoliosis, and susceptibility to malignant hyperthermia provoked by anesthesia. We present two unrelated cases of Bailey-Bloch congenital myopathy descendants of non-consanguineous parents, which were investigated for delayed psychomotor development and generalized weakness. To the best of our knowledge, these are the first descriptions of CMYP13 in Brazil. In both patients, we found the previously described pathogenic missense variant p.Trp284Ser in homozygosity. CONCLUSION: We seek to highlight the need for screening for CMYP13 in patients expressing the typical phenotype of the disease even in the absence of Lumbee Native American ancestry, and to raise awareness to possible complications like malignant hyperthermia in Bailey-Bloch congenital myopathy.

Neuropsychological and quality of life outcomes in PKU patients: expert recommendations of assessment tools in Brazil / Desfechos neuropsicológicos e de qualidade de vida em pacientes com PKU: recomendações de especialistas sobre ferramentas de avaliação no Brasil

Abstract Background Phenylketonuria (PKU) is an inborn error of metabolism caused by deficient activity of phenylalanine hydroxylase. In Brazil, the National Neonatal Screening Program enables early treatment of patients with PKU, which prevents them from developing severe neurological damage and mental disabilities. However, between 20 and 30% of early-treated patients with PKU present focal cognitive deficits, including deficits in working memory, processing speed, and psychiatric symptoms such as anxiety, depression, and attention deficit hyperactivity disorder (ADHD). Therefore, age-specific neuropsychiatric and cognitive tests are important components of PKU patient care. To date, there are no officially approved guidelines or recommendations of tools in Portuguese validated for use in Brazil that could be applied to assess these parameters in patients with PKU. Objective To recommend tools validated for use in Brazil that can be used in daily clinical practice to assess quality of life and neuropsychological outcomes in patients with PKU. Methods Six Brazilian experts discussed about eligible tools based on their clinical experience, the feasibility of their use in clinical routines, and their availability in public health services. Before the meeting, an independent review of the literature was conducted to identify the currently validated tools in Brazil, using the MEDLINE and SciELO databases. Results The experts recommended nine tools to assess quality of life (Peds-QL, SF-36 or WHOQOL-bref), executive function (BRIEF or Bayley-III), IQ (SONR 2½-7[a] or WASI) and ADHD (MTA-SNAP-IV and ASRS). Conclusions These instruments may be easily incorporated into clinical practice and improve the quality of multidisciplinary care of patients with PKU.

Resumo Antecedentes A fenilcetonúria (PKU) é um erro inato do metabolismo causado pela atividade deficiente da fenilalanina hidroxilase. No Brasil, o Programa Nacional de Triagem Neonatal permite o tratamento precoce de pacientes com PKU, o que os impede de desenvolver danos neurológicos e deficiências intelectuais graves. No entanto, já foi descrito que de 20 a 30% dos pacientes tratados precocemente com PKU apresentam déficits cognitivos focais, incluindo déficits na memória de trabalho, velocidade de processamento e sintomas psiquiátricos como ansiedade, depressão e Transtorno de Déficit de Atenção e Hiperatividade (TDAH). Neste sentido, testes neuropsiquiátricos e cognitivos são componentes importantes no cuidado destes pacientes. Atualmente, não existe um compêndio científico ou recomendações de ferramentas validadas em português para avaliar a saúde mental em pacientes brasileiros com PKU. Objetivo Recomendar ferramentas validadas localmente para avaliar a qualidade de vida e aspectos neuropsicológicos de pacientes com PKU. Métodos Seis especialistas brasileiros discutiram as ferramentas mais apropriadas com base em suas experiências clínicas, a viabilidade de realizar as avaliações na rotina clínica, e o acesso às ferramentas na saúde pública. Antes da reunião, foi realizada uma revisão independente da literatura para identificar as ferramentas validadas no Brasil, utilizando as bases de dados MEDLINE e Scielo. Resultados Os especialistas recomendaram nove ferramentas para avaliar a qualidade de vida (Peds-QL, SF-36 ou WHOQOL-bref), função executiva (BRIEF ou Bayley-III), QI (SONR 2½-7[a] ou WASI) e TDAH (MTA-SNAP-IV e ASRS). Conclusões Estes instrumentos podem ser facilmente incorporados na prática clínica e melhorar a qualidade dos cuidados multidisciplinares dos pacientes com PKU.

Neuropsychological and quality of life outcomes in PKU patients: expert recommendations of assessment tools in Brazil.

BACKGROUND: Phenylketonuria (PKU) is an inborn error of metabolism caused by deficient activity of phenylalanine hydroxylase. In Brazil, the National Neonatal Screening Program enables early treatment of patients with PKU, which prevents them from developing severe neurological damage and mental disabilities. However, between 20 and 30% of early-treated patients with PKU present focal cognitive deficits, including deficits in working memory, processing speed, and psychiatric symptoms such as anxiety, depression, and attention deficit hyperactivity disorder (ADHD). Therefore, age-specific neuropsychiatric and cognitive tests are important components of PKU patient care. To date, there are no officially approved guidelines or recommendations of tools in Portuguese validated for use in Brazil that could be applied to assess these parameters in patients with PKU. OBJECTIVE: To recommend tools validated for use in Brazil that can be used in daily clinical practice to assess quality of life and neuropsychological outcomes in patients with PKU. METHODS: Six Brazilian experts discussed about eligible tools based on their clinical experience, the feasibility of their use in clinical routines, and their availability in public health services. Before the meeting, an independent review of the literature was conducted to identify the currently validated tools in Brazil, using the MEDLINE and SciELO databases. RESULTS: The experts recommended nine tools to assess quality of life (Peds-QL, SF-36 or WHOQOL-bref), executive function (BRIEF or Bayley-III), IQ (SONR 2½-7[a] or WASI) and ADHD (MTA-SNAP-IV and ASRS). CONCLUSION: These instruments may be easily incorporated into clinical practice and improve the quality of multidisciplinary care of patients with PKU.

ANTECEDENTES: A fenilcetonúria (PKU) é um erro inato do metabolismo causado pela atividade deficiente da fenilalanina hidroxilase. No Brasil, o Programa Nacional de Triagem Neonatal permite o tratamento precoce de pacientes com PKU, o que os impede de desenvolver danos neurológicos e deficiências intelectuais graves. No entanto, já foi descrito que de 20 a 30% dos pacientes tratados precocemente com PKU apresentam déficits cognitivos focais, incluindo déficits na memória de trabalho, velocidade de processamento e sintomas psiquiátricos como ansiedade, depressão e Transtorno de Déficit de Atenção e Hiperatividade (TDAH). Neste sentido, testes neuropsiquiátricos e cognitivos são componentes importantes no cuidado destes pacientes. Atualmente, não existe um compêndio científico ou recomendações de ferramentas validadas em português para avaliar a saúde mental em pacientes brasileiros com PKU. OBJETIVO: Recomendar ferramentas validadas localmente para avaliar a qualidade de vida e aspectos neuropsicológicos de pacientes com PKU. MéTODOS: Seis especialistas brasileiros discutiram as ferramentas mais apropriadas com base em suas experiências clínicas, a viabilidade de realizar as avaliações na rotina clínica, e o acesso às ferramentas na saúde pública. Antes da reunião, foi realizada uma revisão independente da literatura para identificar as ferramentas validadas no Brasil, utilizando as bases de dados MEDLINE e Scielo. RESULTADOS: Os especialistas recomendaram nove ferramentas para avaliar a qualidade de vida (Peds-QL, SF-36 ou WHOQOL-bref), função executiva (BRIEF ou Bayley-III), QI (SONR 2½-7[a] ou WASI) e TDAH (MTA-SNAP-IV e ASRS). CONCLUSãO: Estes instrumentos podem ser facilmente incorporados na prática clínica e melhorar a qualidade dos cuidados multidisciplinares dos pacientes com PKU.

Apresentação clínica de osteogênese XV em um menino brasileiro de 4 anos / Clinical presentation of osteogenesis imperfecta XV in a four-year-old brazilian boy

Introdução: Osteogênese Imperfeita (OI) é uma doença genética rara com fragilidade óssea. A classificação inclui muitos tipos. Além do risco de recorrência, o manejo pode variar com o tipo de OI. Relato do caso: Apresentamos um paciente do sexo masculino nascido com 39 semanas, de pais não consanguíneos e saudáveis. A hidrocefalia foi diagnosticada no pré-natal. Com 50 dias de vida, detectamos muitas fraturas e calos ósseos. O teste molecular identificou uma deleção em homozigose do éxon 4 do gene WNT1. Considerações finais: Concluímos que o caso apresentado tinha características clínicas de OI XV, e o teste molecular foi fundamental para o diagnóstico preciso e aconselhamento genético.

Introduction: Osteogenesis Imperfecta (OI) is a rare genetic disease with bone fragility. The classification includes many types. In addition, the risk of a recurrence, the management can vary with the kind of OI. Case report: We report a male patient born at 39 weeks from non-consanguineous healthy parents. The patient was diagnosed with Hydrocephalus at prenatal. At 50 days of life, we detected many fractures and bone calluses. The molecular test identified a homozygous deletion of exon 4 of the WNT1 gene. Final considerations: We conclude this case had clinical features of OI XV, and the molecular test was fundamental for the precise diagnosis and the genetic counseling.

Dental treatment before surgery in a patient with cleft lip and palate: case report / Efeito do Cissus quadrangularis na cicatrização de fraturas em animais de laboratório

Introduction: orofacial clefts are common congenital malformations with an important social, psychological, and economic impact. The treatment of this condition may include different surgical procedures that previously require an adequate oral condition. Case report: we report a case of dental treatment before palatoplasty in a male patient of 17 years-old with bilateral cleft lip and palate and lesion in the jugal mucosa. Final considerations: the adequacy of the oral environment is a fundamental step in the treatment of patients with orofacial clefts and aims to restore oral health regardless of the degree of complexity of the dental treatment through the reduction of the pathogenic microbiota, elimination of retentive niches, instructions on diet and adequate oral hygiene and constant patient motivation.

Objetivos: as fissuras orofaciais são malformações congênitas comuns, com importante impacto social, psicológico e econômico. O tratamento dessa condição pode incluir vários procedimentos cirúrgicos que requerem previamente uma adequada condição bucal. Relato de caso: Relatamos o caso de tratamento odontológico prévio a palatoplastia em um paciente do gênero masculino de 17 anos de idade, com fissura transforame incisivo bilateral e lesão em mucosa jugal. Considerações finais: A adequação do meio bucal é uma etapa fundamental no tratamento de pacientes com fissuras orofaciais e visa restabelecer a saúde bucal independente do grau de complexidade do tratamento odontológico por meio da redução da microbiota patogênica, eliminação de nichos retentivos, orientações sobre dieta e higiene bucal adequada e motivação constante do paciente.

Sanfilippo syndrome type B: Analysis of patients diagnosed by the MPS Brazil Network.

Mucopolysaccharidosis type IIIB is a rare autosomal recessive disorder characterized by deficiency of the enzyme N-acetyl-alpha-d-glucosaminidase (NAGLU), caused by biallelic pathogenic variants in the NAGLU gene, which leads to storage of heparan sulfate and a series of clinical consequences which hallmark is neurodegeneration. In this study clinical, epidemiological, and biochemical data were obtained from MPS IIIB patients diagnosed from 2004-2019 by the MPS Brazil Network ("Rede MPS Brasil"), which was created with the goal to provide an easily accessible and comprehensive investigation of all MPS types. One hundred and ten MPS IIIB patients were diagnosed during this period. Mean age at diagnosis was 10.9 years. Patients were from all over Brazil, with a few from abroad, with a possible cluster of MPS IIIB identified in Ecuador. All patients had increased urinary levels of glycosaminoglycans and low NAGLU activity in blood. Main clinical symptoms reported at diagnosis were coarse facies and neurocognitive regression. The most common variant was p.Leu496Pro (30% of alleles). MPS IIIB seems to be relatively frequent in Brazil, but patients are diagnosed later than in other countries, and reasons for that probably include the limited awareness about the disease by health professionals and the difficulties to access diagnostic tests, factors that the MPS Brazil Network is trying to mitigate.

Genotype-phenotype studies in a large cohort of Brazilian patients with Hunter syndrome.

Mucopolysaccharidosis type II (MPS II) is an X-linked inherited disease caused by pathogenic variants in the IDS gene, leading to deficiency of the lysosomal enzyme iduronate-2-sulfatase and consequent widespread storage of glycosaminoglycans, leading to several clinical consequences, with progressive manifestations which most times includes cognitive decline. MPS II has wide allelic and clinical heterogeneity and a complex genotype-phenotype correlation. We evaluated data from 501 Brazilian patients diagnosed with MPS II from 1982 to 2020. We genotyped 280 of these patients (55.9%), which were assigned to 206 different families. Point mutations were present in 70% of our patients, being missense variants the most frequent. We correlated the IDS pathogenic variants identified with the phenotype (neuronophatic or non-neuronopathic). Except for two half-brothers, there was no discordance in the genotype-phenotype correlation among family members, nor among MPS II patients from different families with the same single base-pair substitution variant. Mothers were carriers in 82.0% of the cases. This comprehensive study of the molecular profile of the MPS II cases in Brazil sheds light on the genotype-phenotype correlation and helps the better understanding of the disease and the prediction of its clinical course, enabling the provision of a more refined genetic counseling to the affected families.

Craniofacial microsomia: Reflections on diagnosis and severity assessment based on a series of cases.

This study aims to discuss diagnostic criteria and severity assessment for craniofacial microsomia (CFM). A series of 61 patients with diverse CFM phenotypes had their clinical data collected by experienced dysmorphologists using a single protocol. Genetic abnormalities were searched through karyotype and chromosomal microarray analysis. Sex ratio, prenatal risk factors, and recurrence rate corroborated the literature. Despite the wide variability of clinical findings, ear disruption was universal. Eight patients were assigned as syndromic, four of whom had demonstrable genetic alterations. The majority of patients (67.2%) fulfilled four known diagnostic criteria, while 9.8% fulfilled one of them. Data strengthened disruptions of the ear and deafness as a semiotically valuable sign in CFM. Facial impairment should consider asymmetry as a mild expression of microsomia. Spinal and cardiac anomalies, microcephaly, and developmental delay were prevalent among extra craniofacial features and should be screened before planning treatment and follow up. The severity index was able to recognize the less and the most affected patients. However, it was not useful to support therapeutic decisions and prognosis in the clinical scenario due to syndromic and non-syndromic phenotypes overlapping. These issues make contemporary the debate on diagnostic methods and disease severity assessment for CFM. They also impact care and etiopathogenetic studies.

Neurological growth and development of children asymptomatic at birth whose mothers had Zika during pregnancy.

INTRODUCTION: Newborn who had Zika vírus but did not show microcephaly at birth may have neuropsychomotor development problems. We aimed to evaluate the developmental and anthropometric milestones of asymptomatic children whose mothers had Zika during pregnancy in Northeastern Brazil in 2015 and 2016. METHODS: We conducted a descriptive cross-sectional case series study of children in Fortaleza born without microcephaly whose mothers had Zika during pregnancy. Home visits were undertaken to evaluate the developmental milestones and gather anthropometric data of the children and to conduct semi-structured interviews with the mothers to identify their socioeconomic and gestational profiles and assess the newborns after birth. RESULTS: In total, 30 cases were identified. Of these, 17 children and their mothers participated in the study. The median age of the mothers at the time of delivery was 26 years. All were symptomatic, and TORCH was negative. At the time of the home visit, all had growth profiles suitable for their age. However, nearly all children (15/17, 88.2%) presented at least one developmental delay, considering their age group. CONCLUSIONS: There were late changes in the neuropsychomotor development of children born to mothers who had Zika during pregnancy, suggesting the need for specialized medical follow-ups.

Defining dysmorphic facial features in congenital Zika syndrome.

Congenital Zika syndrome (CZS) constitutes a recently identified malformation caused by Zika virus infection during pregnancy. Limited data is available to date on the facial dysmorphic features of these patients. This study evaluated the facial dysmorphisms of children with CZS, compared with clinically healthy children, using clinical examination and standardized photographic images. Sixty-three children with CZS (9.70 ± 3.2 months-age), and 31 Controls (8.67 ± 6.2 months-age) joined the study. Seven out of 15 indices differed between groups: midfacial height (MFH)/horizontal facial reference (HFR) (p = .0003), interalar distance/HFR (p = .0027), nasal root depth/MFH (p = .0030), posterior nasal length/MFH (p = .0002), vertical position of the ear/MFH (p <.0001), ear length/MFH (p = .0005), chin height/total facial height (CH/TFH) (p <.0001). A CH/TFH of 0.229 showed 93.9% sensitivity and 80.6% specificity in diagnosing CZS. Children with CZS had broad, short faces, decreased intercanthal distance, short posterior nasal length, prominent nasal root, broad nasal wings, and high-set and long ears. Increased chin height index provided the most accurate diagnostic potential.

Neurological growth and development of children asymptomatic at birth whose mothers had Zika during pregnancy

Abstract INTRODUCTION: Newborn who had Zika vírus but did not show microcephaly at birth may have neuropsychomotor development problems. We aimed to evaluate the developmental and anthropometric milestones of asymptomatic children whose mothers had Zika during pregnancy in Northeastern Brazil in 2015 and 2016. METHODS: We conducted a descriptive cross-sectional case series study of children in Fortaleza born without microcephaly whose mothers had Zika during pregnancy. Home visits were undertaken to evaluate the developmental milestones and gather anthropometric data of the children and to conduct semi-structured interviews with the mothers to identify their socioeconomic and gestational profiles and assess the newborns after birth. RESULTS: In total, 30 cases were identified. Of these, 17 children and their mothers participated in the study. The median age of the mothers at the time of delivery was 26 years. All were symptomatic, and TORCH was negative. At the time of the home visit, all had growth profiles suitable for their age. However, nearly all children (15/17, 88.2%) presented at least one developmental delay, considering their age group. CONCLUSIONS: There were late changes in the neuropsychomotor development of children born to mothers who had Zika during pregnancy, suggesting the need for specialized medical follow-ups.

Unmet needs in PKU and the disease impact on the day-to-day lives in Brazil: Results from a survey with 228 patients and their caregivers.

BACKGROUND: Accumulation of phenylalanine (Phe) due to deficiency in the enzyme phenylalanine hydroxylase (PAH), responsible for the conversion of Phe into tyrosine leads to Phenylketonuria (PKU), a rare autosomal recessive inborn error of metabolism with a mean prevalence of approximately 1:10,000 to 1:15,000 newborns. Physical, neurocognitive and psychiatric symptoms include neurodevelopmental disorder as intellectual disability and autism spectrum disorder. The most common treatments such as low-Phe diet and supplements may decrease blood Phe concentrations, but neuropsychological, behavioral and social issues still occur in some patients. This study aimed to better understand (i) the Brazilian population's knowledge about newborn screening (NBS), the main diagnostic method for PKU, as well as (ii) the impacts of phenylketonuria in the daily lives of patients and parents. METHODS: Two surveys in Real World Data format gathering of Brazilian residents by online questionnaires with (i) 1000 parents of children up to 5 years old between March and April 2019; (ii) 228 PKU patients and caregivers in March 2019. The survey was conducted in partnership with Abril Publisher and two Brazilian patient associations: Metabolic Mothers and SAFE Brasil, for families with rare diseases and PKU patients, respectively. RESULTS: The first questionnaire shows that 93% of parents recognize the importance of NBS and 92% report that their children have undergone the test. Still, two out of ten participants did not know what the exam is or what it is for. From the second questionnaire nine out of ten patients had their PKU diagnosis by NBS. Although strict dietary controls for PKU were claimed by 44% of respondents from second questionnaire, 55% assume not following all nutritionist recommendations and 52% did not maintain routinely Phe control levels. In addition, 53% said they had high spending on medical appointments, therapies and purchase of special foods. CONCLUSIONS: Despite the lack of understanding, the awareness of NBS importance is present in the studied population. The early diagnosis of most PKU patients in the study corroborates with neonatal screening central role of PKU early detection. The difficulty in adhering to dietary adjustments and the possibility that current and new therapeutic strategies other than diet could be determinant to achieve the recommended Phe levels.

A síndrome de Cri Du Chat em adolescentes / The Cri du Chat syndrome in adolescents

Introdução: A síndrome do miado do gato ou síndrome 5p é uma doença congênita rara causada por uma anormalidade cromossômica. Relato do caso: Apresentamos o caso de uma paciente de 13 anos com características dismórficas leves. O retardo mental era grave, com comportamento mal adaptativo e hiperatividade. O diagnóstico citogenético da anormalidade cromossômica 46 XX del 5pter-->p13 foi estabelecido. Conclusão: O diagnóstico precoce dessa doença é necessário para a qualidade de vida dos pacientes, mas esse diagnóstico é difícil de ser realizado em pacientes que foram vistos, pela primeira vez, em idade mais avançada.

Introduction: Cat cry syndrome or 5p- syndrome is a rare congenital disease caused by a chromosomal abnormality. Case report: The case of a thirteen-year-old female patient with mild dysmorphic features is presented. Mental retardation is severe, with maladaptive behavior and hyperactivity. The cytogenetic diagnosis of chromosomal abnormality karyotype 46 XX del 5pterp13 has been established. Conclusions: We concluded that early diagnosis of this disease is necessary for patients' quality of life, but this diagnosis is difficult to make in patients who were first seen at an older age.

A large family with CYLD cutaneous syndrome: medical genetics at the community level.

Germline mutations in the cylindromatosis gene (CYLD) are associated with a rare autosomal dominant disease known as CYLD cutaneous syndrome (CCS). Patients present multiple neoplasms originating from skin appendages. Here, we investigated the main clinical and molecular features of a large family with CCS having lived in a small Brazilian town for 6 generations, making its prevalence significantly high. We observed a predominance of the disease among males and a wide phenotypic variation. A high frequency of basal cell carcinomas among affected people was found. The mutation c.2806C>T, p.Arg936* in the CYLD gene was detected in all patients. In this work, a geographical cluster of CCS was found, which raised some community genetics issues related not only to the high prevalence of a rare disease in a limited area but also to the strong social stigma associated with the disease.

Glycogen storage diseases: Twenty-seven new variants in a cohort of 125 patients.

BACKGROUND: Hepatic glycogen storage diseases (GSDs) are a group of rare genetic disorders in which glycogen cannot be metabolized to glucose in the liver because of enzyme deficiencies along the glycogenolytic pathway. GSDs are well-recognized diseases that can occur without the full spectrum, and with overlapping in symptoms. METHODS: We analyzed a cohort of 125 patients with suspected hepatic GSD through a next-generation sequencing (NGS) gene panel in Ion Torrent platform. New variants were analyzed by pathogenicity prediction tools. RESULTS: Twenty-seven new variants predicted as pathogenic were found between 63 variants identified. The most frequent GSD was type Ia (n = 53), followed by Ib (n = 23). The most frequent variants were p.Arg83Cys (39 alleles) and p.Gln347* (14 alleles) in G6PC gene, and p.Leu348Valfs (21 alleles) in SLC37A4 gene. CONCLUSIONS: The study presents the largest cohort ever analyzed in Brazilian patients with hepatic glycogenosis. We determined the clinical utility of NGS for diagnosis. The molecular diagnosis of hepatic GSDs enables the characterization of diseases with similar clinical symptoms, avoiding hepatic biopsy and having faster results.

Dental alterations on panoramic radiographs of patients with osteogenesis imperfecta in relation to clinical diagnosis, severity, and bisphosphonate regimen aspects: a STROBE-compliant case-control study.

OBJECTIVE: This study aimed to assess the prevalence of dental findings on panoramic radiographs (PRs) of patients with osteogenesis imperfecta (OI) and correlate these results with epidemiologic and medical data. STUDY DESIGN: A case-control study was conducted with 24 patients with OI and 48 sex- and age-matched controls. Demographic, clinical, and bisphosphonate regimen-related data were recorded. The outcome variables were the presence or absence of dental alterations in PRs. Mann-Whitney U test, Pearson's χ2 test, and multinomial logistic regression analysis (95% confidence interval) were used (significance level of 5%). RESULTS: OI type 4 demonstrated a high prevalence (62.5%), followed by type 1 (37.5%). With regard to prevalence associated with severity, the moderate form was the most prevalent (P = .028). The mean time of intravenous pamidronate regimen was 6.6 ± 4.4 years. Dentinogenesis imperfecta was observed in 75% of patients with OI, and this group showed a high prevalence of dental abnormalities in comparison with controls (P < .05). Bisphosphonate therapy was associated with ectopic teeth (P = .007) and tooth impaction (P = .033). Pulp obliteration was significant with bisphosphonate treatment over a period of 7 years (P = .026). CONCLUSIONS: This study found a significant prevalence of dental alterations in patients with OI, and certain alterations were associated with bisphosphonate therapy, indicating its influence on the dentin-related physiopathology.