Assuntos
Predisposição Genética para Doença , Encefalopatia Hepática/genética , Falência Hepática/genética , Falência Hepática/patologia , Proteínas de Membrana/genética , Proteínas Mitocondriais/genética , Biópsia por Agulha , Causas de Morte , Progressão da Doença , Feminino , Humanos , Imuno-Histoquímica , Lactente , Recém-Nascido , Expectativa de Vida , Testes de Função Hepática , Linhagem , Fenótipo , Medição de Risco , Taxa de Sobrevida , Gêmeos MonozigóticosRESUMO
Orofaciodigital syndrome type I and X-linked recessive Joubert syndrome are known ciliopathic disorders that are caused by pathogenic variants in OFD1 gene. Endocrine system involvement with these conditions is not well described. We present the first report of a newborn male with a novel hemizygous variant in OFD1 gene c.515T>C, (p.Leu172Pro) resulting in X-linked Joubert syndrome and orofaciodigital features with complete pituitary gland aplasia and subsequent severe hypoplasia of peripheral endocrine glands. This clinical report expands the phenotypic spectrum of endocrine system involvement in OFD1-related disorders and suggests that OFD1 gene may be related to pituitary gland development.
Assuntos
Anormalidades Múltiplas/diagnóstico , Anormalidades Múltiplas/genética , Cerebelo/anormalidades , Anormalidades do Olho/diagnóstico , Anormalidades do Olho/genética , Genes Ligados ao Cromossomo X , Doenças Renais Císticas/diagnóstico , Doenças Renais Císticas/genética , Mutação , Fenótipo , Proteínas/genética , Retina/anormalidades , Alelos , Genótipo , Humanos , Recém-Nascido , Imageamento por Ressonância Magnética , Masculino , Síndromes Orofaciodigitais/diagnóstico , Síndromes Orofaciodigitais/genética , Linhagem , Hipófise/anormalidades , Radiografia , Sequenciamento do ExomaRESUMO
Variable lung disease was documented in 2 infants with heterozygous TBX4 mutations; their clinical presentations, pathology, and outcomes were distinct. These findings demonstrate that TBX4 gene mutations are associated with neonatal respiratory failure and highlight the wide spectrum of clinicopathological outcomes that have implications for patient diagnosis and management.
Assuntos
Mutação/genética , Insuficiência Respiratória/genética , Insuficiência Respiratória/patologia , Proteínas com Domínio T/genética , Feminino , Humanos , Recém-Nascido , MasculinoRESUMO
We evaluated a family with three siblings, two of whom ages 2 years and 19 months, had long segment colonic agangliosis and anisocoria. The mother also had anisocoria. All three affected family members were mildly dysmorphic with a flat facial profile, square appearance to the face, depressed nasal bridge, and anteverted nares. Genetic testing identified a novel heterozygous mutation, c.234C>G, resulting in a premature stop codon in exon 1 of the PHOX2B gene. Screening for neural crest tumors was performed in the siblings and to date has been negative. This family supports a strong association between non polyalanine tract mutations, autonomic dysfunction, and Hirschsprung disease, but suggests mutation outside of the polyalanine tract may not dictate severe phenotype with significant respiratory compromise. A unique finding in this family is the association of congenital heart disease in two of the affected patients. These malformations may be a sporadic isolated finding or the result of environmental factors or a modifying allele. Given the association between congenital heart disease and aberrant neural crest cell development, however, findings are suggestive that congenital heart disease may be a rare feature of PHOX2B mutation which has not been previously reported.