RESUMO
Heterozygous activating variants in platelet-derived growth factor, beta (PDGFRB) are associated with phenotypes including Kosaki overgrowth syndrome (KOGS), Penttinen syndrome and infantile myofibromatosis (IM). Here, we present three new cases of KOGS, including a patient with a novel de novo variant c.1477A > T p.(Ser493Cys), and the oldest known individual age 53 years. The KOGS phenotype includes characteristic facial features, tall stature, scoliosis, hyperelastic thin skin, lipodystrophy, variable intellectual and neurological deterioration, and abnormalities on brain imaging. Long-term outcome is unknown. Our cases confirm the phenotypic spectrum includes progressive flexion contractures, camptodactyly, widely spaced teeth, and constriction rings. We also propose novel occasional features including craniosynostosis, ocular pterygia, anterior chamber cleavage syndrome, early osteoporosis, increased pigmentation, recurrent haematomas, predisposition to cellulitis, nail dystrophy, carpal tunnel syndrome, recurrent hypoglycaemia in infancy, joint dislocation, and splenomegaly. Importantly, we report fusiform aneurysm of the basilar artery in two patients. Complications include thrombosis and stroke in the oldest reported patient and fatal rupture at the age of 21 in the patient with the novel variant. We conclude that cerebrovascular complications are part of the phenotypic spectrum of KOGS and KOGS-like disorders and suggest vascular imaging is indicated in these patients.
Assuntos
Transtornos Cerebrovasculares/etiologia , Transtornos Cerebrovasculares/genética , Variação Genética/genética , Transtornos do Crescimento/complicações , Transtornos do Crescimento/genética , Receptor beta de Fator de Crescimento Derivado de Plaquetas/genética , Adulto , Humanos , Masculino , Pessoa de Meia-Idade , FenótipoAssuntos
Esclerose Múltipla/etiologia , Adulto , Fatores Etários , Artrite/genética , Traumatismos do Nascimento/complicações , Queimaduras/complicações , Transtornos Cerebrovasculares/genética , Diabetes Mellitus/genética , Características da Família , Feminino , Cardiopatias/genética , Humanos , Hipersensibilidade/genética , Hipertensão/genética , Infecções/complicações , Irlanda , Masculino , Procedimentos Cirúrgicos Menores/efeitos adversos , Esclerose Múltipla/genética , Neoplasias/genética , Classe Social , Fatores Socioeconômicos , Procedimentos Cirúrgicos Operatórios/efeitos adversos , Tonsilectomia/efeitos adversos , Extração Dentária/efeitos adversos , Tuberculose/genética , Vacinação/efeitos adversos , Ferimentos e Lesões/complicaçõesRESUMO
A 13-year-old male presented with new onset seizures, sagittal sinus thrombosis with cerebral hemorrhage, and extensive venous thrombosis of the lower limbs. Laboratory investigation demonstrated combined deficiency of protein C, protein S, and antithrombin III. He and his 17-year-old sister had a mental retardation-multiple anomaly syndrome associated with microcephaly, unusual facies, and lax connective tissue. Their dysmorphology included elongated faces with narrow forehead, arched eyebrows, large mouth with down-turned corners, malformed teeth, and furrowed tongue. Both had Marfanoid habitus with lax joints, pectus excavatum, kyphoscoliosis, and flat narrow feet. The most likely diagnosis for these siblings is the autosomal recessive Cohen syndrome of mental retardation, congenital hypotonia with Marfanoid habitus, microcephaly, pleasant affect, micrognathia, and open mouth with prominent incisors. The sagittal sinus thrombosis, left frontal intracranial hemorrhage, carotid aneurysm, tortuous descending aorta, and deep venous thrombosis suffered by the male sibling adds the Cohen syndrome to genetic vasculopathies that may be associated with stroke.