RESUMEN
Mixed vascular naevus (MVN) is characterized by the co-occurrence of telangiectatic capillary malformation and naevus anaemicus, which can appear as a pure cutaneous phenotype or be combined with systemic manifestations such as brain malformations, neurological abnormalities and musculoskeletal disorders. Recently, GNA11 and GNAQ somatic mutations have been reported in some patients with isolated and syndromic MVN. We report three children with MVN syndrome with generalized cutaneous manifestations and a number of systemic associations not reported to date, including ophthalmological anomalies, musculoskeletal abnormalities such as Sprengel deformity and posterior vertebral fusion anomalies, and septal heart defects. We also confirm a somatic mutation of GNA11 in both telangiectatic naevus and naevus anaemicus in two of our patients and discuss a possible common pathogenic mechanism underlying the different manifestations of the syndrome. Currently, there are no guidelines for the evaluation of patients with MVN syndrome, but according to the different known aspects of the disease, a complete clinical examination should be made, and complementary laboratory and imaging tests should be considered.
Asunto(s)
Capilares/anomalías , Subunidades alfa de la Proteína de Unión al GTP/genética , Mutación , Nevo/genética , Telangiectasia/genética , Malformaciones Vasculares/genética , Anomalías Múltiples/genética , Anomalías Múltiples/patología , Capilares/patología , Preescolar , Femenino , Humanos , Lactante , Masculino , Nevo/patología , Síndrome , Telangiectasia/patología , Malformaciones Vasculares/patologíaRESUMEN
INTRODUCTION: Congenital muscular hyperplasia of the hand is a rarely described entity, characterized by the presence of aberrant or accessory muscles in the hypothenar eminence, which has been always reported as sporadic anomaly in the medical literature. The aim of this paper is to report a series of cases with a phenotype of aberrant muscle hyperplasia associated with PIK3CA mutations. MATERIAL AND METHODS: We describe a retrospective series of cases followed at our institution between 2008 and 2020, with a unique phenotypein the context of PIK3CA mutations. RESULTS: A total of 6 patients were included (4 males and 2 females), who presented with an enlargement of the hypothenar eminence of the hand and peculiar wrinkling of the overlying skin, associated with ulnar deviation of the metacarpo-phalangeal joints. In all cases, variable degrees of congenital overgrowth of the ipsilateral limb were observed. Skin punch biopsy (5 mm diameter and 3-5 mm depth) was performed on 4 patients, where striated muscle hyperplasia and the presence of striated muscular fibers in the dermis and hypodermis were observed in all of them. Genetic studies revealed PIK3CA mutation in 3 of the 4 patients whose affected tissue was analyzed, in a mosaic state ranging from 3 to 8% (His1047Arg, Glu542Lys, and Cys420Arg, 1 case each). CONCLUSION: Aberrant muscular hyperplasia of the hand is a well-recognized entity scarcely described in association with PIK3CA spectrum disorder in the pediatric population. The role of PIK3CA in muscle overgrowth is not yet well understood.
INTRODUCCION: La hiperplasia muscular congénita de la mano es una entidad rara, caracterizada por la presencia de músculos aberrantes o accesorios en la eminencia hipotenar, que siempre se ha descrito en la literatura médica como una anomalía esporádica. El objetivo de este artículo es informar de una serie de casos con fenotipo de hiperplasia muscular aberrante asociada a mutaciones del PIK3CA. MATERIAL Y METODOS: Serie retrospectiva de casos atendidos en nuestro centro entre 2008 y 2020, con un fenotipo único en el contexto de las mutaciones del PIK3CA. RESULTADOS: Se incluyeron un total de 6 pacientes (4 masculinos y 2 femeninos) con ensanchamiento de la eminencia hipotenar de la mano y arrugamiento peculiar de la piel suprayacente, asociado a desviación ulnar de las articulaciones metacarpofalángicas. En todos los casos se observaron grados variables de sobrecrecimiento congénito del miembro ipsilateral. Se realizó biopsia cutánea por punch (5 mm de diámetro y 3-5 mm de profundidad) en 4 pacientes con hiperplasia muscular y presencia de fibras musculares estriadas en dermis e hipodermis. Los estudios genéticos revelaron mutación del PIK3CA en 3 de los 4 pacientes, cuyo tejido afectado fue enviado a analizar, con mosaicismo de entre el 3 y el 8% (His1047Arg, Glu542Lys y Cys420Arg respectivamente). CONCLUSION: La hiperplasia muscular aberrante de la mano es una entidad reconocida pero escasamente descrita en asociación con síndromes relacionados con el PIK3CA en la población pediátrica. A día de hoy sigue desconociéndose el papel del PIK3CA en el sobrecrecimiento muscular.
Asunto(s)
Mano , Niño , Fosfatidilinositol 3-Quinasa Clase I/genética , Femenino , Humanos , Hiperplasia , Masculino , Mutación , Estudios RetrospectivosRESUMEN
Introducción: La hiperplasia muscular congénita de la mano esuna entidad rara, caracterizada por la presencia de músculos aberranteso accesorios en la eminencia hipotenar, que siempre se ha descrito enla literatura médica como una anomalía esporádica. El objetivo de esteartículo es informar de una serie de casos con fenotipo de hiperplasiamuscular aberrante asociada a mutaciones del PIK3CA. Material y métodos: Serie retrospectiva de casos atendidos ennuestro centro entre 2008 y 2020, con un fenotipo único en el contextode las mutaciones del PIK3CA. Resultados: Se incluyeron un total de 6 pacientes (4 masculinos y2 femeninos) con ensanchamiento de la eminencia hipotenar de la manoy arrugamiento peculiar de la piel suprayacente, asociado a desviaciónulnar de las articulaciones metacarpofalángicas. En todos los casos seobservaron grados variables de sobrecrecimiento congénito del miembroipsilateral. Se realizó biopsia cutánea por punch (5 mm de diámetro y 3-5mm de profundidad) en 4 pacientes con hiperplasia muscular y presenciade fibras musculares estriadas en dermis e hipodermis. Los estudiosgenéticos revelaron mutación del PIK3CA en 3 de los 4 pacientes, cuyotejido afectado fue enviado a analizar, con mosaicismo de entre el 3 y el8% (His1047Arg, Glu542Lys y Cys420Arg respectivamente). Conclusión: La hiperplasia muscular aberrante de la mano es unaentidad reconocida pero escasamente descrita en asociación con síndromes relacionados con el PIK3CA en la población pediátrica. A día dehoy sigue desconociéndose el papel del PIK3CA en el sobrecrecimientomuscular.(AU)
Introduction: Congenital muscular hyperplasia of the hand is ararely described entity, characterized by the presence of aberrant oraccessory muscles in the hypothenar eminence, which has been alwaysreported as sporadic anomaly in the medical literature. The aim of thispaper is to report a series of cases with a phenotype of aberrant musclehyperplasia associated with PIK3CA mutations. Material and Methods: We describe a retrospective series of casesfollowed at our institution between 2008 and 2020, with a unique phe-notypein the context of PIK3CA mutations. Results: A total of 6 patients were included (4 males and 2 females),who presented with an enlargement of the hypothenar eminence ofthe hand and peculiar wrinkling of the overlying skin, associated withulnar deviation of the metacarpo-phalangeal joints. In all cases, variabledegrees of congenital overgrowth of the ipsilateral limb were observed.Skin punch biopsy (5 mm diameter and 3-5 mm depth) was performedon 4 patients, where striated muscle hyperplasia and the presence ofstriated muscular fibers in the dermis and hypodermis were observedin all of them. Genetic studies revealed PIK3CA mutation in 3 of the 4patients whose affected tissue was analyzed, in a mosaic state rangingfrom 3 to 8% (His1047Arg, Glu542Lys, and Cys420Arg, 1 case each). Conclusion: Aberrant muscular hyperplasia of the hand is a well-recognized entity scarcely described in association with PIK3CA spec-trum disorder in the pediatric population. The role of PIK3CA in muscleovergrowth is not yet well understood.(AU)
Asunto(s)
Humanos , Masculino , Femenino , Preescolar , Niño , Hiperplasia , Coristoma , Sobrecrecimiento Gingival , Deformidades Congénitas de la Mano , Estudios Retrospectivos , PediatríaRESUMEN
The Publisher regrets that this article is an accidental duplication of an article that has already been published, https://doi.org/10.36959/472/363. The duplicate article has therefore been withdrawn. The full Elsevier Policy on Article Withdrawal can be found at https://www.elsevier.com/about/our-business/policies/article-withdrawal.
RESUMEN
Smith-Kingsmore syndrome (SKS) OMIM #616638, also known as MINDS syndrome (ORPHA 457485), is a rare autosomal dominant disorder reported so far in 23 patients. SKS is characterized by intellectual disability, macrocephaly/hemi/megalencephaly, and seizures. It is also associated with a pattern of facial dysmorphology and other non-neurological features. Germline or mosaic mutations of the mTOR gene have been detected in all patients. The mTOR gene is a key regulator of cell growth, cell proliferation, protein synthesis and synaptic plasticity, and the mTOR pathway (PI3K-AKT-mTOR) is highly regulated and critical for cell survival and apoptosis. Mutations in different genes in this pathway result in known rare diseases implicated in hemi/megalencephaly with epilepsy, as the tuberous sclerosis complex caused by mutations in TSC1 and TSC2, or the PIK3CA-related overgrowth spectrum (PROS). We here present 4 new cases of SKS, review all clinical and molecular aspects of this disorder, as well as some characteristics of the patients with only brain mTOR somatic mutations.
