Clinical report: one year of treatment of Proteus syndrome with miransertib (ARQ 092).
Cold Spring Harb Mol Case Stud
; 6(1)2020 02.
Article
em En
| MEDLINE
| ID: mdl-32014856
ABSTRACT
A 20-yr-old man with Proteus syndrome (PS) and somatic mosaicism of the AKT1 c.49G > A p.(E17K) variant had asymmetric overgrowth of the right frontal and facial bones, asymmetric spinal overgrowth with thoracolumbar scoliosis, dilatation of the inferior vena cava, testicular cystadenoma, bilateral knee deformities, macrodactyly, and apparent intellectual disability. Miransertib (ARQ 092) is an oral, allosteric, selective pan-AKT inhibitor initially developed for cancer therapeutics, now being evaluated for the treatment of PS. After baseline evaluation, the patient started unblinded treatment of 10 mg oral miransertib daily (â¼5 mg/m2/day), escalated to 30 mg daily (â¼15 mg/m2/day), and then to 50 mg daily (â¼25 mg/m2/day) after 3 mo of treatment. Adverse events included dry mouth, one episode of gingivostomatitis, and loose, painful dentition due to preexisting periodontal disease, all of which resolved spontaneously. After 11 mo of treatment, the patient reported improved general well-being, increased mobility of the ankle, spine, and hands, a subjective decrease in size of the right facial bone overgrowth, and reduced areas of cerebriform connective tissue nevi on the soles. Whole-body MRI findings were stable without apparent disease progression. We conclude that 1 yr of treatment with miransertib was beneficial in this case.
Palavras-chave
abnormal plantar dermatoglyphics; abnormal subcutaneous fat tissue distribution; attention deficit hyperactivity disorder; hypercoagulability; hypertrophy of skin of soles; intellectual disability; macrodactyly of finger; macrodactyly of toe; moderate; neoplasia of the male external genitalia; ovarian neoplasm; overgrowth; postnatal macrocephaly; prominent veins on trunk; proportionate tall stature; testicular neoplasm; venous malformation
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Síndrome de Proteu
/
Inibidores de Proteínas Quinases
/
Aminopiridinas
/
Imidazóis
Tipo de estudo:
Diagnostic_studies
/
Etiology_studies
Limite:
Adult
/
Humans
/
Male
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article