RESUMEN
BACKGROUND: Fibrous Dysplasia/McCune-Albright Syndrome (FD/MAS) is characterized by a spectrum of manifestations that may include fibrous dysplasia of bone and multiple endocrinopathies. AIM: To describe the clinical spectrum, the study and follow-up of patients with FD/MAS cared at our institution. MATERIAL AND METHODS: Review of medical records of 12 pediatric and adult patients (11 women) who met the clinical and genetic diagnostic criteria for FD/ MAS. RESULTS: The patients' mean age at diagnosis was 4.9 ± 5.5 years. The most common initial clinical manifestation was peripheral precocious puberty (PPP) in 67% of patients and 75% had café-au-lait spots. Fibrous dysplasia was present in 75% of patients and the mean age at diagnosis was 7.9 ± 4.7 years. Ten patients had a bone scintigraphy, with an age at the first examination that varied between 2 and 38 years of age. The most frequent location of dysplasia was craniofacial and appendicular. No patient had a recorded history of cholestasis, hepatitis, or pancreatitis. In four patients, a genetic study was performed that was positive for the pathogenic variant of guanine nucleotide binding protein, alpha stimulating (GNAS). CONCLUSIONS: These patients demonstrate the variable nature of the clinical presentation and study of FD/MAS. It is essential to increase the index of diagnostic suspicion and adherence to international recommendations.
Asunto(s)
Humanos , Femenino , Preescolar , Niño , Adolescente , Adulto , Adulto Joven , Pubertad Precoz/etiología , Pubertad Precoz/genética , Displasia Fibrosa Ósea/diagnóstico por imagen , Displasia Fibrosa Poliostótica/genética , Displasia Fibrosa Poliostótica/diagnóstico por imagen , Chile/epidemiología , Manchas Café con Leche/genéticaRESUMEN
BACKGROUND: Fibrous Dysplasia/McCune-Albright Syndrome (FD/MAS) is characterized by a spectrum of manifestations that may include fibrous dysplasia of bone and multiple endocrinopathies. AIM: To describe the clinical spectrum, the study and follow-up of patients with FD/MAS cared at our institution. MATERIAL AND METHODS: Review of medical records of 12 pediatric and adult patients (11 women) who met the clinical and genetic diagnostic criteria for FD/ MAS. RESULTS: The patients' mean age at diagnosis was 4.9 ± 5.5 years. The most common initial clinical manifestation was peripheral precocious puberty (PPP) in 67% of patients and 75% had café-au-lait spots. Fibrous dysplasia was present in 75% of patients and the mean age at diagnosis was 7.9 ± 4.7 years. Ten patients had a bone scintigraphy, with an age at the first examination that varied between 2 and 38 years of age. The most frequent location of dysplasia was craniofacial and appendicular. No patient had a recorded history of cholestasis, hepatitis, or pancreatitis. In four patients, a genetic study was performed that was positive for the pathogenic variant of guanine nucleotide binding protein, alpha stimulating (GNAS). CONCLUSIONS: These patients demonstrate the variable nature of the clinical presentation and study of FD/MAS. It is essential to increase the index of diagnostic suspicion and adherence to international recommendations.
Asunto(s)
Displasia Fibrosa Ósea , Displasia Fibrosa Poliostótica , Pubertad Precoz , Adulto , Humanos , Niño , Femenino , Preescolar , Adolescente , Adulto Joven , Displasia Fibrosa Poliostótica/diagnóstico por imagen , Displasia Fibrosa Poliostótica/genética , Chile/epidemiología , Displasia Fibrosa Ósea/diagnóstico por imagen , Pubertad Precoz/etiología , Pubertad Precoz/genética , Manchas Café con Leche/genéticaRESUMEN
Partial monosomy 21 results in a great variability of clinical features that may be associated with the size and location of the deletion. In this study, we report a 22-month-old girl who showed a 45,XX,add(12)(p13)dn,-21 karyotype. The final cytogenomic result was 45,XX,der(12)t(12;21)(p13;q22.11) dn,-21.arr[hg19] 21q11.2q22.11(14824453_33868129)×1 revealing a deletion from 21pter to 21q22.11. Clinical manifestation of the patient included hypertonia, a long philtrum, epicanthic folds, low-set ears, and café-au-lait macules - a phenotype considered as mild despite the relatively large size of the deletion compared to patients from the literature.
Asunto(s)
Anomalías Múltiples/genética , Manchas Café con Leche/genética , Deleción Cromosómica , Cromosomas Humanos Par 21/ultraestructura , Cara/anomalías , Hipertonía Muscular/genética , Cromosomas Humanos Par 21/genética , Discapacidades del Desarrollo/genética , Femenino , Pérdida Auditiva Bilateral/genética , Humanos , Recién Nacido , Cariotipificación , Fenotipo , Escoliosis/genéticaRESUMEN
Neurofibromatosis type 1 (NF1; OMIM#162200) is a common neurocutaneous disorder that is characterized by multiple café-au-lait, skinfold freckling, Lisch nodules, and neurofibromas. Mutations in the NF1 gene, which encodes the neurofibromin protein, have been identified as the pathogenic gene of NF1. In this study, we present a clinical and molecular study of a Chinese patient with giant café-au-lait in NF1. The patient showed >6 café-au-lait spots on the body, axillary freckling, and multiple subcutaneous neurofibromas. He also had a malignant peripheral nerve sheath tumor and bone abnormalities. The germline mutational analysis of the NF1 gene revealed a novel missense mutation in exon 13. It is a novel heterozygous nucleotide G>A transition at position 2241 of the NF1 gene. We found no mutation in malignant peripheral nerve sheath tumor DNA from this patient. This expands the database for NF1 gene mutations in NF1. Its absence in the normal chromosomes suggests that it is responsible for the NF1 phenotype. To our knowledge, this is the first case of giant café-au-lait macule in NF1 associated with a malignant peripheral nerve sheath tumor and bone abnormality.
Asunto(s)
Pueblo Asiatico/genética , Huesos/anomalías , Manchas Café con Leche/genética , Mutación/genética , Neoplasias de la Vaina del Nervio/complicaciones , Neurofibromatosis 1/genética , Neurofibromina 1/genética , Adolescente , Secuencia de Aminoácidos , Secuencia de Bases , Manchas Café con Leche/complicaciones , Manchas Café con Leche/diagnóstico por imagen , Análisis Mutacional de ADN , Humanos , Masculino , Datos de Secuencia Molecular , Neoplasias de la Vaina del Nervio/diagnóstico por imagen , Neoplasias de la Vaina del Nervio/genética , Neurofibromatosis 1/complicaciones , Neurofibromatosis 1/diagnóstico por imagen , Neurofibromina 1/química , Radiografía Abdominal , Tomografía Computarizada por Rayos XRESUMEN
Bilateral segmental neurofibromatosis is a rare condition characterized by the occurrence of neurofibromas and/or café-au-lait spots limited to an area or segment of the body bilaterally. It is caused by a postzygotic mutation in the neurofibromatosis type I gene, resulting in a phenotype of genetic mosaicism. This report describes a case of bilateral segmental neurofibromatosis with multiple nodules sitting on a café-au-lait spot.
Asunto(s)
Manchas Café con Leche/patología , Neurofibromatosis 1/patología , Manchas Café con Leche/genética , Niño , Genes de Neurofibromatosis 1 , Humanos , Masculino , Mosaicismo , Neurofibromatosis 1/genética , FenotipoRESUMEN
BACKGROUND: McCune-Albright Syndrome (MAS) is characterized by precocious puberty, "cafe au lait" skin lesions and polyostotic fibrous dysplasia. It is caused by 4 post-zygotic mutations of G alpha s protein with a mosaic distribution. AIM: To describe the clinical presentation and to investigate the presence of the Arg by his substitution (R201H) in 14 girls with MAS. PATIENTS AND METHODS: We performed a clinical analysis of the patients and specific allele PCR in DNA obtained from leukocytes. RESULTS: Twelve of 14 patients presented with precocious puberty, one with cyclical vaginal bleeding and one with pathological bone fractures. Eight girls had polyostotic fibrous dysplasia, one had hyperthyroidism, four had pathological fractures, ten had ovarian cysts, six had breast hyperpigmentation and ten had "cafe au lait" skin lesions. We detected the R2O1H mutation in 10 of 14 patients. We found no difference in the severity of symptoms or in the age of presentation between the patients with and without the mutation. CONCLUSIONS: The R201H mutation can be detected in white blood cells, in approximately 70% of cases. Patients exhibit wide clinical variability with the same molecular defect. This suggests that tissues have different proportions of mutant cells.
Asunto(s)
Manchas Café con Leche/genética , Displasia Fibrosa Poliostótica/genética , Leucocitos , Pubertad Precoz/genética , Adolescente , Estudios de Casos y Controles , Niño , Análisis Mutacional de ADN , Femenino , Humanos , Masculino , Reacción en Cadena de la Polimerasa , SíndromeRESUMEN
Single café-au-lait macules (CALMs) are common in the pediatric population and in most children represent a normal finding. It is important to recognize whether the presence of multiple CALMs in a particular patient is normal or indicates an association with a multisystem disorder. This article addresses issues concerning the prevalence, genetics, and natural history of CALMs in the general population and reviews disorders in which CALMs are present as a characteristic trait.