Neonatal Smith-Kingsmore syndrome: case report and literature review / 中国新生儿科杂志

Objective:To study the clinical and genetic features of neonatal Smith-Kingsmore syndrome (SKS).Methods:The clinical data of a newborn with SKS admitted to our hospital in November 2021 were reviewed. Using "Smith-Kingsmore", "rapamycin gene", "newborn", "premature infant", "the mammalian target of rapamycin", "MTOR", "mTOR", "Smith-Kingsmore syndrome", "megalencephaly", "macrocephaly" and "hemimegalencephaly" as keywords, databases including CNKI, Wanfang Database, VIP database, PubMed, Embase, Web of Science and the Cochrane Library were searched from the date of establishment to January 1, 2022. The clinical and genetic features of neonatal SKS from published literature were summarized.Results:The case admitted to our hospital was a male preterm infant. The presenting symptoms were groan and hypotonia. The facial abnormalities included macrocrania, ocular hypertelorism, depressed nasal bridge and low-set ears. Brain MRI showed lateral ventricle enlargement. Whole-genome sequencing (WGS) showed mTOR gene nonsense heterozygous mutation (NM_004958.4:c.7255G>A:p.Glu2419Lys). Neither father nor mother had any pathogenic gene mutations. The infant had seizure at 2-month and phenobarbital was effective reducing seizure. Gross motor delay was present at 3-month. Sixteen related articles were retrieved, including eight articles with 10 neonatal cases. Among them, 6 cases were male. The main clinical features were megalencephaly or hemimegalencephaly (9/10), facial developmental malformation (8/10), hypotonia (6/10), large-for-gestational age (LGA) infants (5/10), cerebral ventricle dilation (4/10) and abnormal corpus callosum (4/10). All the gene mutations were missense mutations, including c.5395G>A(p.Glu1799Lys) mutation in 5 cases, c.4448G>T(p.Cys1483Phe) mutation in 1 case, c.4448G>T(p.Cys1483Tyr) mutation in 1 case, c.7235A>T(p.Asp2412Val) mutation in 1 case, c.5663T>G(p.Phe1888Cys) mutation in 1 case, c.5390C>T(p.Thr1799IIe) mutation in 1 case.Conclusions:The clinical phenotypes of neonatal SKS are diverse, including megalencephaly, facial malformation, LGA and hypotonia. The brain MR findings included (hemi) megalencephaly, cerebral ventricle dilation and corpus callosum hypoplasia. Most of the gene mutations are missense mutations and c.5395G>A(p.Glu1799Lys) is the hotspot.

Síndrome de Proteus y síndrome de West en lactante femenina / Proteus Syndrome and West Syndrome in female infant

Introducción: El síndrome de Proteus es un raro síndrome hamartomoso congenito con manifestaciones neuroectodérmicas, de carácter progresivo y grado de severidad variable. Objetivo: Presentar un caso clínico donde se combinan dismorfias faciales, crecimiento excesivo de una hemicara, macrocráneo y manifestaciones neurológicas. Presentación del caso: lactante de 10 meses, femenina, con antecedentes de embarazo de riesgo, hija de madre adolescente, con exposición fetal a tabaco, marihuana y alcohol; nació con macrocefalia, dismorfia facial con hemihipertrofia derecha y nevó hiperpigmentado que comenzó con espasmos infantiles desde el primer mes vida y se diagnosticó síndrome west de etiología estructural con hemimegancefalia derecha. Cumple los criterios clínicos de síndrome de Proteus y tuvo una respuesta favorable con control de los espasmos, mejoría de la hipsarritmia y del desarrollo psicomotor, con tratamiento combinado de hormona adenocorticotrópica y vigabatrina. Conclusiones: el síndrome de Proteus se caracteriza por crecimiento exagerado en varios tejidos (epidérmico, conectivo, óseo, adiposo y endotelial) durante la embriogénesis, por lo que las manifestaciones clínicas suelen ser evidentes desde el nacimiento o en los primeros años de vida, se relaciona con un grupo de casos con malformaciones del sistema nervioso central y síndrome de West(AU)

Introduction: Proteus syndrome is a rare congenital hamartoma syndrome with neuroectodermal manifestations of progressive kind and a degree of variable severity. Objective: To present a clinical case where facial diysmorphias, the excessive growth of a hemicara, a macro-skull, and neurological manifestations are combined. Case presentation: A 10-month-old female infant with a history of risky pregnancy, daughter of a teenage mother, with fetal exposure to tobacco, marijuana and alcohol. She was born with macrocephaly, facial dysmorphia with right hemihypertrophy, hyperpigmented nevus that started with infantile spasms from the first month of life; and West syndrome of structural etiology with right hemimegalencephaly was diagnosed. The patient meets the clinical criteria of Proteus syndrome and she had a favorable response to the combined treatment of adrenocorticotropic hormone and Vigabatrin with control of spasms, improvement of hypsarrhythmia and psychomotor development. Conclusions: Proteus syndrome is characterized by exaggerated growth in various tissues (epidermal, connective, bone, adipose and endothelial) during embryogenesis, so that clinical manifestations are usually evident from birth or in the first years of life. It is related with a group of cases with malformations of the central nervous system and West syndrome(AU)

Asimetría cerebral: enfoque diagnóstico / Brain Asymmetry: Diagnosis Approach

Las asimetrías cerebrales son entidades clínicas frecuentes encontradas en la práctica diaria del radiólogo. Son causadas por diversas etiologías que pueden ser agrupadas en congénitas y adquiridas. Las congénitas son aquellas que se presentan por condiciones durante la vida intrauterina, mientras que las adquiridas ocurren después del nacimiento, usualmente antes de los 2 años de edad. En los estudios por imágenes, las asimetrías cerebrales están dadas por aumento o disminución del volumen de la totalidad o de parte de un hemisferio cerebral y esta variabilidad en el volumen cerebral puede ser por causas fisiológicas, también conocidas como normales o por causas no fisiológicas secundarias a procesos congénitos o adquiridos, que dan lugar a desproporción de un hemisferio cerebral con respecto al otro. En este artículo se propone un enfoque diagnóstico práctico para abordar este hallazgo, donde, evaluando el hemisferio cerebral y el tamaño ventricular, se puede desplegar una serie de posibles diagnósticos diferenciales.

Brain asymmetries are a common finding for radiologists and may be caused by multiple etiologies, including congenital and acquired causes. Congenital causes are conditions that appear during the fetal life, while the acquired causes occur after birth and usually before 2 years of age. In cross-sectional imaging, brain asymmetries are characterized by enlargement or atrophy of all or a part of a cerebral hemisphere. This variability in brain volume may be caused by physiological causes or by non-physiological causes that are secondary to congenital and acquired processes, causing an asymmetry in the hemispheres. In this article we propose a practical diagnostic approach to brain asymmetries based on the evaluation of the cerebral hemisphere and ventricular system size.

Isolated Nonsyndromic Hemimegalencephaly Presenting at Neonatal Age - A Case Report.

Hemimegalencephaly (HME) is a relatively rare sporadic brain malformation characterized by enlargement of one cerebral hemisphere. It has a variable presentation and may include partial seizures to epileptic encephalopathy, hemiparesis and psychomotor retardation. Epilepsy associated with HME is usually refractory to antiepileptic drugs and requires surgical intervention. Diagnosis of HME may be delayed in the absence of detailed examination and high index of suspicion giving rise to poor quality of life prior to surgery. We report, a case of a male neonate, with radiological features of HME picked up within seven days after birth. This was possible as antenatal ultrasonography was showing dilatation of the right lateral ventricle of the fetus. Baby had macrocephaly at birth and refractory convulsions from day two of life. Convulsions were managed successfully. Baby was discharged on necessary treatment and parents were given appropriate counseling. Careful examination and high index of suspicion can help in early diagnosis and better outcome. Our review of the literature did not yield any reports of patients with isolated non-syndromic HME presenting with refractory seizures as initial presentation in the neonatal age group. To our knowledge, this is the first report of its kind.

Hemimegalencefalia. Presentación de caso / Hemimegalencephaly. A Case Report

La hemimegalencefalia es un trastorno de la proliferación neuronal que produce un excesivo crecimiento de todo o parte de un hemisferio cerebral. Su patogenia aún se desconoce. Se presenta el caso de un paciente adulto, con antecedentes de epilepsia desde la infancia temprana, rebelde a tratamiento farmacológico, asociada a retraso mental moderado, el cual fue ingresado para control de crisis epilépticas. La resonancia magnética nuclear de cráneo mostró asimetría de hemisferios cerebrales con corteza derecha ensanchada y escasa diferenciación de la sustancia gris y blanca. Es objetivo de esta presentación exponer una causa infrecuente de epilepsia, cuyo diagnóstico por lo general se hace en la infancia. La hemimegalencefalia debe sospecharse en epilepsias de inicio precoz y difícil manejo, sobre todo cuando se asocian a macrocefalia y retardo del desarrollo psicomotor. La indicación oportuna de la neuroimagen permite establecer el diagnóstico y brindar otras opciones terapéuticas.

Hemimegalencephaly is a disorder of neuronal proliferation that causes an overgrowth of all or part of a cerebral hemisphere. Its pathogenesis is still unknown. We present the case of an adult patient with a history of childhood-onset epilepsy, which was refractory to medical treatment and associated with moderate mental retardation. He was admitted to the hospital for seizure control. Magnetic resonance imaging showed hemispheric asymmetry with enlarged right cerebral hemisphere and poor gray-white matter differentiation. The objective of this paper is to present a rare cause of epilepsy that is usually diagnosed during childhood. Hemimegalencephaly should be suspected in cases of early onset of difficult-to-control epilepsy, especially when associated with macrocephaly and delayed psychomotor development. Timely indication for neuroimaging allows establishing the diagnosis and providing other treatment options.

Happle-Tinschert Syndrome: Report of a Case with Hemimegalencephaly

Happle-Tinschert syndrome is a disorder causing unilateral segmentally arranged basaloid follicular hamartomas of the skin associated with ipsilateral osseous, dental and cerebral abnormalities including tumors. Although a case with hemimegalencephaly was previously described, this is the first report of Happle-Tinschert syndrome with discrepant short left leg, ipsilateral skin lesions, hemimegalencephaly and frontal polymicrogyria.

Neonatal Hemimegalencephaly Accompanying Band Heterotopia: Sonographic Finding and Correlation with MR Finding

There are many reports of hemimegalencephaly on MRI. However, there have been a few reports of sonographic diagnosis of the disease in a neonate. A one-day-old female infant was diagnosed as hemimegalencephaly accompanying band heterotopia on cranial sonography, which showed 4 a four-layered patterns of hypoechoic cortex, thick band-like hyperechoic subcortical white matter, inner hypoechoic heterotopia, and hyperechoic unmyelinated periventricular white matter. The sonographic patterns corresponded well with MRI findings on the second day of life. To the best of my knowledge, the author is the first to reports on the US findings and MR correlation of hemimegalencephaly.

Hypomelanosis of Ito

Hypomelanosis of Ito (HI) is a rare neurocutaneous syndrome with characteristic whirled hypopigmented skin lesions and neurological manifestations. Less consistently, there may be non-neurological manifestations that include ophthalmic, musculoskeletal, craniofacial, cardiac, genitourinary, and gastrointestinal involvements. We report a case of HI, with typical skin lesions in association with hemimegalencephaly, seizures and mental retardation along with the hitherto unreported repetitive hand movements such as seen in Rett syndrome.

A Case of Tuberous Sclerosis with Hemimegalencephaly / 대한소아신경학회지

Hemimegalencephaly and tuberous sclerosis complex are distinct and rare conditions which are characterized by malformations of cortical developments. Hemimegalencephaly is a cerebral malformation of unknown pathophysiology characterized by asymmetry of the hemispheres and cortical dysplasia. Tuberous sclerosis complex(TSC) is an autosomal dominant neurocutaneous disorder characterized by the formation of hamartomatous lesion in multiple organ systems. While they are currently thought to be unrelated, there are similar cases in the literature and it is conceivable that an abnormality in early cortical development could lead to both conditions in an individual. We report here a first Korean case of unusual association of hemimegalencephaly and tuberous sclerosis complex with mutation in the TSC2 gene, who presented initially frequent partial seizures and infantile spasms.

A case of hemimegalencephaly with congenital foot deformity / 대한주산의학회잡지

Hemimegalencephaly is a rare congenital malformation of the cortical development arising from abnormal proliferation of anomalous neuronal and glial cells. The characteristic clinical manifestations are macrocephaly, psycomotor retardation, intractable seizure and hemihypertrophy of face, body and extremities, but musculoskeletal deformities are reported only in case of epidermal nevus syndrome. We report a case of hemimegalencephaly that was associated with foot deformity, without symptoms and signs of epidermal nevus syndrome.

Trastorno de migración neuronal: a propósito de un caso / Neuronal migration disorder: a clinic case

El Trastorno de Migración Neuronal (TMN) se caracteriza por una serie de malformaciones del Sistema Nervioso Central (SNC) que ocurre entre el segundo y quinto mes de gestación; de etiologías variadas. Producen grados diversos de retardo psicomotriz, convulsiones y otras manifestaciones dependiendo de las áreas afectadas. Presentamos el caso de una paciente de 3 meses de edad, sexo femenino, que presentó convulsiones caracterizadas por espasmos en flexión desde el nacimiento, frecuentes y de corta duración, resistentes a tratamiento anticonvulsivante, sin antecedentes infecciosos, obtenida por cesárea sin complicaciones. Se realizó una TAC, un EEG y una RMN, revelando lisencefalia, hemimegalencefalia y esquizoencefalia del hemisferio cerebral derecho e hipoplasia del cuerpo calloso.

The Neuronal Migration Disorder is characterized by a series of malformations of central nervous system that occur between the second and fifth month of gestation; of different etiologies. Have many grades of psychomotor retarded, seizures and others manifestations depending of affect areas. Present a clinic case of a patient of 3 month old, feminine sex, who presents seizures by spasm in flexion since born, frequent and short durations, resistant a anticonvulsant treatment, without infection record, obtained by caesarean without complications. Performed a TAC, a EEG and a RMN, showed a lisencephaly, hemimegalencephaly and schizoencephaly of right cerebral hemisphere and callus body hipoplasia.

Hemimegalencephaly: A case report

Hemimegalencephaly is an uncommon sporadic congenital malformation of the central nervous system characterized by enlargement of one cerebral hemisphere with cranial asymmetry, hemiparesis, epilepsy, and mental retardation. This report deals with a 12-month-old girl with intractable seizure and developmental delay, who revealed hemispheric asymmetry and enlarged right cerebral hemisphere. MRI scan revealed asymmetric enlargement of right cerebral hemisphere with lissencephaly and multifocal calcification. She underwent right frontal lobectomy and parietal cortical resection, but died of complication of surgery. Histological features included loss of cortical lamination, large atypical neurons, neuronal heterotopia, and astrocytosis with dystrophic calcification. The heterotopic neurons in the white matter were suggestive of aberrant neuronal migration.

A Case of Hypomelanosis of Ito with Hemimegalencephaly

Hypomelanosis of Ito is a congenital neurocutaneous syndrome with a particular pattern of streaks, patches and swirling hypopigmentation over variable portions of the body surface. Multiple extracutaneous abnormalities involving the central nervous system, musculoskeletal structures and the eyes occur in over two-thirds of the cases. This report describes a patient with typical unilateral cutaneous lesions associated with extracutaneous features, including hypertrophy of the cerebral hemisphere contralateral to the cutaneous hypopigmentation. Chromosomal analysis of fibroblasts of depigmented skin obtained from the patients showed mosaicism.

A Case of Hemimegalencephaly with Intraventricular Hemorrhage and Multifocal Intraparenchymal Hemorrage on Deep White Matter of Periventricular Area

Hemimegalencephaly is a rare congenital anomaly characterized by a intractable seizure an infantile death. This disease is a migrational disorder with enlargement of unilateral hemisphere, abnormal gyration of the cortex, the presence of large and atypical neuron, hetero trophic neuron at subcortical area and proliferation of astrocyte ect. We observed a neonate with neonatal seizure, and the radiological evaluation revealed abnormal enlargement of right hemisphere, intraventricular hemorrhage of both ventricle and multifocal intraparenchymal hemorrhage on deep white matter of periventricular area on both sides. We used the phenobarbital for treatment of seizure. After phenobarbital treatment. The seizure was controlled. A review of literature was also presented briefly

Two cases of hemimegalencephaly

No abstract available.