RESUMO
BACKGROUND: Costello syndrome (CS) is a rare genetic condition characterized by dysregulation of the signaling pathway, phenotypic alteration due to fetal macrosomia or growth retardation, facial abnormalities, loose skin, cardiovascular abnormalities, and a variable degree of intellectual disability. CASE PRESENTATION: We describe the case of a 20-month-old male patient with fetal macrosomia and polyhydramnios, presenting psychomotor development delay and growth limitation during the first months of life. CS was diagnosed at four months of age after detecting a variant of the HRAS gene c.35G > C (p.G12A). A clinical description of his condition was recorded throughout his life, including cardiovascular diseases, endocrine disorders, and recurrent infections. At 20 months of age, after presenting events of marked hypotonia and generalized seizures, brain magnetic resonance revealed symmetrical lesions of the infra- and supratentorial white matter in both cerebral hemispheres, which resulted in the diagnosis of cerebral leukodystrophy. The patient had a rapid and progressive deterioration that eventually led to death. CONCLUSIONS: This is the first report of a case of CS in Peru. In addition, this is a case that presented with multisystemic conditions culminating in leukodystrophy, which is a rare event according to the literature.
Assuntos
Anormalidades Cardiovasculares , Síndrome de Costello , Deficiência Intelectual , Gravidez , Feminino , Humanos , Masculino , Lactente , Síndrome de Costello/complicações , Síndrome de Costello/diagnóstico , Síndrome de Costello/genética , Macrossomia Fetal , Genes ras , Deficiência Intelectual/genéticaRESUMO
Costello syndrome is part of the RASopathies, a group of neurocardiofaciocutaneous syndromes caused by deregulation of the RAS mitogen-activated protein kinase pathway. Heterozygous mutations in HRAS are responsible for Costello syndrome, with more than 80% of the patients harboring the specific p.Gly12Ser variant. These individuals show a homogeneous phenotype. The clinical characteristics of the Costello syndrome individuals harboring rarer HRAS mutations are less understood, due to the small number of reported cases. Here, we describe the phenotypic spectrum of five additional individuals with HRAS c.38G>A; p.Gly13Asp, including one with somatic mosaicism, and review five previously described cases. The facial and hair abnormalities of the HRAS p.Gly13Asp individuals differ from the typical pattern observed in those showing the common HRAS (p.Gly12Ser) mutation, with less coarse facial features and slow growing, sparse hair with abnormal texture, the latter resembling the pattern observed in Noonan syndrome-like disorder with loose anagen hair and individuals harboring another amino acid substitution in HRAS (p.Gly13Cys). Although some individuals with HRAS p.Gly13Asp developed papillomata and vascular proliferation lesions, no malignant tumors occurred, similar to what was reported for individuals harboring the HRAS p.Gly13Cys. The fact that no malignant tumors were described in these individuals does not allow definitive conclusions about the risk for cancer development. It remains to be determined if substitutions of amino acid 13 in HRAS (p.Gly13Asp and p.Gly13Cys) increase the risk of tumor development.
Assuntos
Anormalidades Múltiplas/genética , Síndrome de Costello/genética , Neoplasias/genética , Proteínas Proto-Oncogênicas p21(ras)/genética , Anormalidades Múltiplas/fisiopatologia , Adolescente , Adulto , Substituição de Aminoácidos/genética , Aminoácidos/genética , Criança , Pré-Escolar , Síndrome de Costello/complicações , Síndrome de Costello/fisiopatologia , Feminino , Mutação em Linhagem Germinativa , Humanos , Masculino , Mosaicismo , Neoplasias/complicações , Neoplasias/fisiopatologia , FenótipoRESUMO
Costello syndrome is a rare multisystem disorder caused by mutations in the proto-oncogene HRAS. Failure to thrive is one of its cardinal clinical features. This study documents that individuals with Costello syndrome have increased resting energy expenditure. We speculate this could be one of the potential mechanisms causing failure to thrive.
Assuntos
Síndrome de Costello/complicações , Metabolismo Energético , Insuficiência de Crescimento/etiologia , Descanso/fisiologia , Adolescente , Adulto , Estudos de Casos e Controles , Criança , Pré-Escolar , Síndrome de Costello/metabolismo , Insuficiência de Crescimento/metabolismo , Feminino , Humanos , Masculino , Proto-Oncogene Mas , Adulto JovemRESUMO
Costello syndrome (CS) is a rare genetic disorder, first described by Costello in 1971, caused by mutations in the HRAS proto-oncogene. Clinical findings include facial dysmorphism, skin disorders, cognitive impairment, cardiac and musculoskeletal defects. There is an increased risk of malignancies in these patients, due to the proto-oncogene mutation, and also sudden death secondary to heart disease. We report a case with characteristic phenotype, highlighting the peculiar skin changes.
Assuntos
Humanos , Feminino , Adulto Jovem , Anormalidades da Pele/patologia , Síndrome de Costello/patologia , Ceratodermia Palmar e Plantar/patologia , Fácies , Síndrome de Costello/complicações , Síndrome de Costello/fisiopatologiaRESUMO
Costello syndrome (CS) is a rare genetic disorder, first described by Costello in 1971, caused by mutations in the HRAS proto-oncogene. Clinical findings include facial dysmorphism, skin disorders, cognitive impairment, cardiac and musculoskeletal defects. There is an increased risk of malignancies in these patients, due to the proto-oncogene mutation, and also sudden death secondary to heart disease. We report a case with characteristic phenotype, highlighting the peculiar skin changes.