Assessment of the tongue frenulum in Beckwith-Wiedemann syndrome: Pre- and post-frenectomy findings.

AIM: To report the pre- and post-frenectomy findings of a patient with Beckwith-Wiedemann syndrome. METHODS AND RESULTS: Clinical case report of a patient with a confirmed genetic-molecular diagnosis of the referred syndrome. The minor was evaluated and reassessed by the protocol for the evaluation of the tongue's frenulum for babies in two moments: pre-surgical and 2 months after the frenectomy. The surgical procedure was performed using the traditional technique and, after the procedure, the minor was breastfed and received photobiomodulation with a red laser. The minor obtained 16 points in the neonatal tongue screening test, indicating the need for a frenectomy. Thus, she was referred to a dentist for surgery. After the surgical procedure, macroglossia was observed as a maternal complaint (previously not mentioned). The wound healing was satisfactory, and the total score obtained in the reapplication of the protocol (five points) showed functional results of improvements in sucking and tongue mobility, justifying the importance of the frenectomy. CONCLUSION: Frenectomy, despite showing macroglossia related to the Beckwith-Wiedemann syndrome, allowed anatomical and functional advances of the tongue in the present clinical case.

Maple syrup urine disease in Brazilian patients: variants and clinical phenotype heterogeneity.

BACKGROUND: Maple syrup urine disease (MSUD) is an autosomal recessive inherited metabolic disease caused by deficient activity of the branched-chain α-keto acid dehydrogenase (BCKD) enzymatic complex. BCKD is a mitochondrial complex encoded by BCKDHA, BCKDHB, DBT, and DLD genes. MSUD is predominantly caused by Variants in BCKDHA, BCKDHB, and DBT genes encoding the E1α, E1ß, and E2 subunits of BCKD complex, respectively. The aim of this study was to characterize the genetic basis of MSUD by identifying the point variants in BCKDHA, BCKDHB, and DBT genes in a cohort of Brazilian MSUD patients and to describe their phenotypic heterogeneity. It is a descriptive cross-sectional study with 21 MSUD patients involving molecular genotyping by Sanger sequencing. RESULTS: Eight new variants predicted as pathogenic were found between 30 variants (damaging and non-damaging) identified in the 21 patients analyzed: one in the BCKDHA gene (p.Tyr120Ter); five in the BCKDHB gene (p.Gly131Val, p.Glu146Glnfs * 13, p.Phe149Cysfs * 9, p.Cys207Phe, and p.Lys211Asn); and two in the DBT gene (p.Glu148Ter and p.Glu417Val). Seventeen pathogenic variants were previously described and five variants showed no pathogenicity according to in silico analysis. CONCLUSION: Given that most of the patients received late diagnoses, the study results do not allow us to state that the molecular features of MSUD variant phenotypes are predictive of clinical severity.

Clinical orofacial and myofunctional manifestations in an adolescent with Noonan Syndrome: a case report / Manifestações clínicas e miofuncionais orofaciais em adolescente com a Síndrome de Noonan: relato de caso

ABSTRACT Noonan syndrome is an autosomal dominant genetic disease with different manifestations, including Speech, Language and Hearing Sciences ones. The authors describe the orofacial and myofunctional manifestations of an adolescent diagnosed with Noonan syndrome, by consulting the Speech, Language and Hearing Sciences record of a 17-year-old male patient, who underwent screening and speech therapy evaluation with a confirmed genetic diagnosis of Noonan syndrome. The results were qualitatively analyzed. The patient had a long facial type, with a disproportion between the lower and middle thirds of the face, ogival palate, and Mallampati class IV. A deficit in mobility and sensitivity of phonoarticulatory organs was also identified, absence of pathological oral and gag reflexes, decreased lip tone and tongue tension, increased speed chewing and inefficient grinding, functional swallowing for assessed consistencies, mild verbal and nonverbal apraxia, and moderate dysarthria. The results confirmed the presence of alterations in the speech-language organs, proving the relevance of the Speech, Language and Hearing Sciences evaluation in Noonan Syndrome, to allow adequate follow-up and treatment.

RESUMO A síndrome de Noonan é uma doença genética autossômica dominante com diferentes manifestações, incluindo as fonoaudiológicas. Os autores descrevem as manifestações miofuncionais orofaciais de um adolescente com diagnóstico de síndrome de Noonan, por meio de consulta ao prontuário fonoaudiológico de um paciente do sexo masculino, dezessete anos, que foi submetido à triagem e avaliação fonoaudiológicas com diagnóstico genético confirmado de síndrome de Noonan. Os resultados foram analisados qualitativamente. O paciente apresentou tipologia facial longa, com desproporção entre os terços inferior e médio da face, palato ogival e Mallampati classe IV. Também foi identificado déficit na mobilidade e sensibilidade dos órgãos fonoarticulatórios, ausência de reflexos orais patológicos e de gag, diminuição de tônus de lábios e de tensão de língua, mastigação com velocidade aumentada e trituração ineficiente, deglutição funcional para as consistências avaliadas, apraxia verbal e não verbal leve, disartria moderada. Os resultados confirmam a presença de alterações morfofuncionais relacionadas aos órgãos fonoarticulatórios, comprovando a relevância da avaliação fonoaudiológica na Síndrome de Noonan, de forma a possibilitar o acompanhamento e tratamento adequados.

Caracterização genético-clínica de pacientes com fenilcetonúriano Estado de Alagoas / Genetic and clinical characterization of patients with phenylketonuria in Alagoas state, Brazil

Objetivos: Caracterizar o perfil genético-clínico de pacientes com fenilcetonúria em Alagoas, diagnosticados e acompanhados pelo Programa Nacional de Triagem Neonatal.Métodos: Pacientes com fenilcetonúria, assistidos pelo Serviço de Referência em Triagem Neonatal de Alagoas, foram submetidos a coleta de sangue para rastrear mutações genéticas determinantes da variação fenotípica da doença. Concomitantemente, os pacientes ou seus responsáveis responderam a um questionário padronizado para coleta de dados clínicos e epidemiológicos.Resultados: Foram acompanhados 20 pacientes, sendo 14 do sexo masculino e seis do sexo feminino, pertencentes a 18 famílias. A idade dos pacientes estudados variou de 3 a 31 anos. Houve consanguinidade parental em 3/18 famílias; recorrência familial 3/18; 3/20 tiveram diagnóstico tardio; 2/20 interromperam temporariamente o tratamento; 1/20 não aderiu ao tratamento; e 6/20 apresentam manifestações clínicas. A análise das mutações foi concluída em 15/20 pacientes. As mutações encontradas no gene da fenilalanina hidroxilase foram: R261Q-homozigose (2 pacientes); V388M/I65T (1); R270K/V388M (1); I65T/L348V (1); IVS10nt11G>A-homozigose (2); V388M/R252W (1); R261Q/I65T (1); IVS10nt11G>A/R252W (1); V388M/IVS10nt11G>A (3); R261Q/R252W (1); R261Q/V388M (1).Conclusões: O genótipo V388M/IVS10nt11G>A foi o mais prevalente. Trinta por cento dos pacientes foram sintomáticos, provavelmente pela natureza das mutações, não adesão ao tratamento, tratamento inadequado e/ou diagnóstico tardio.

Aims: Characterizing the genetic/clinical profile of patients diagnosed with Phenylketonuria in Alagoas, monitored by the National Program of Newborn Screening. Methods: Patients with phenylketonuria, assisted by the Reference Center for Neonatal Screening of Alagoas , underwent blood sampling for detecting genetic determinants for the phenotypic variability of the disease. Concomitantly, patients or their guardians answered a standardized questionnaire for collection of clinical and epidemiological data. Results: Twenty patients (14 males and 6 females), belonging to 18 families, were monitored. Age ranged from 3-31 (mean age 10.35).We found parental consanguinity in 3/18 families; familial recurrence was 3/18; 3/20 had late diagnosis; 2/20 interrupted treatment for some time; 1/20 did not adhere to treatment; and 6/20 had clinical manifestations. Analysis of mutations was concluded in 15/20 patients. Mutations found in the phenylalanine hydroxylase gene were: R261Q-homozygous (2 patients); V388M/I65T (1); R270K/V388M (1); I65T/L348V (1); IVS10nt11G>A-homozygous(2); V388M/R252W (1); R261Q/I65T (1); IVS10nt11G>A/R252W (1); V388M/IVS10nt11G>A (3); R261Q/R252W (1); R261Q/V388M (1).