RESUMO
BACKGROUND: Noonan syndrome with multiple lentigines (NSML), formerly known as LEOPARD syndrome, is an autosomal-dominant disorder characterised by lentigines, EKG abnormalities, ocular hypertelorism, pulmonic stenosis, abnormal genitalia, growth retardation and deafness. There is significant clinical overlap between NSML and other disorders that result from dysregulated rat sarcoma/mitogen-activated protein kinase pathway (RASopathies). Except for neurofibromatosis type 1, other RASopathies are not known to be typically associated with neurogenic tumours. METHODS AND RESULTS: We evaluated patients from three families with pigmentary skin lesions, progressive neuropathy, enlarged nerves, massive burden of paraspinal tumours (neurofibroma was confirmed in one patient) and a clinical diagnosis of NSML. All patients had a mutation in the protein tyrosine phosphatase catalytic domain of the PTPN11 gene; two unrelated patients had the p.Thr468Met mutation, while the family consisting of two affected individuals harboured the p.Thr279Cys mutation. Molecular analysis performed on hypertrophic nerve tissue did not disclose a second somatic hit in NF1, PTPN11, NF2 or SMARCB1 genes. CONCLUSIONS: Neurogenic tumours and hypertrophic neuropathy are unusual complications of NSML and may be an under-recognised manifestation that would warrant surveillance. Our observation may also have implications for other disorders caused by RAS-pathway dysregulation.
Assuntos
Síndrome LEOPARD/genética , Neurofibroma/genética , Proteína Tirosina Fosfatase não Receptora Tipo 11/genética , Neoplasias da Coluna Vertebral/genética , Adolescente , Adulto , Feminino , Humanos , Hipertrofia/genética , Síndrome LEOPARD/etiologia , Masculino , Pessoa de Meia-Idade , Proteínas Quinases Ativadas por Mitógeno/genética , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Mutação , Neurofibroma/etiologia , Neurofibromatose 1/etiologia , Neurofibromatose 1/genética , Síndrome de Noonan/etiologia , Síndrome de Noonan/genética , Neoplasias da Coluna Vertebral/etiologiaRESUMO
PURPOSE OF REVIEW: The diagnosis of many childhood endocrine disorders can be facilitated by an awareness of the associated dermatologic findings. In this review, we will survey examples of endocrine disorders in children that include a prominent or diagnostic dermatologic sign/symptom. RECENT FINDINGS: A key concept is that skin findings often accompany hormonal conditions, both those of hormone excess and hormone deficiency/resistance. Some dermatologic signs may also represent the hallmark lesion, or provide the first clinical sign in childhood, for both familial tumoral and nontumoral syndromes. Moreover, skin as an endocrine organ itself may provide new avenues both to understand disease mechanisms as well as to provide targeted therapy. SUMMARY: Early diagnosis, often aided by recognition of a keynote dermatologic lesion, may permit prompt, timely treatment that, in some cases, may even prove life saving. Conversely, when these associated signs go undetected or misdiagnosed, therapeutic intervention may be delayed unnecessarily.
