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1.
BMJ Case Rep ; 14(12)2021 Dec 30.
Artigo em Inglês | MEDLINE | ID: mdl-34969807

RESUMO

Megalencephaly-capillary malformation-polymicrogyria syndrome (MCAP) is a rare disorder that arises as a result of a somatic mosaic mutation in the PIK3CA gene. It characteristically presents with postnatal or congenital megalencephaly, cutaneous capillary malformations, postaxial polydactyly and often segmental or focal body overgrowth. We report a 7-year-old boy with known MCAP who was diagnosed at around 10 months old with a mosaic change in the PIK3CA gene. He was found to have hall-mark clinical signs; macrocephaly and four-limb postaxial polydactyly. Since diagnosis, he has had multiple clinical features, most of which typically present in children with MCAP. He has now been diagnosed with autism spectrum disorder (ASD), demand avoidance and is under assessment for attention deficit hyperactivity disorder. Although some cases have been raised to the M-CM Network, to our knowledge this is the first case of ASD in MCAP to be reported in the literature.


Assuntos
Transtorno do Espectro Autista , Megalencefalia , Polimicrogiria , Transtorno do Espectro Autista/genética , Capilares/anormalidades , Criança , Humanos , Lactente , Masculino , Megalencefalia/diagnóstico por imagem , Megalencefalia/genética , Mutação , Polimicrogiria/diagnóstico por imagem , Polimicrogiria/genética , Malformações Vasculares
2.
AJNR Am J Neuroradiol ; 42(10): 1878-1883, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34385141

RESUMO

BACKGROUND AND PURPOSE: Definitions of fetal microcephaly and macrocephaly are debatable. A better understanding of their long-term prognoses would help guide parental education and counseling. This study aimed to explore the correlation between 2D and 3D fetal brain MR imaging biometry results and the long-term neurodevelopmental outcomes. MATERIALS AND METHODS: This analysis is a historical cohort study. Fetal brain biometry was measured on 2D and 3D MR imaging using a volumetric MR imaging semiautomated algorithm. We measured and assessed the following brain structures: the supratentorial brain volume and cerebellar volume and cerebellar volume/supratentorial brain volume ratio, in addition to commonly used 2D brain MR imaging biometric variables, including occipitofrontal diameter, biparietal diameter, and transcerebellar diameter. Microcephaly was defined as ≤ 3rd percentile; and macrocephaly, as ≥ 97th percentile, corresponding to -2 SDs and +2 SDs. The neurodevelopmental outcome of this study cohort was evaluated using the Vineland-II Adaptive Behavior Scales, and the measurements were correlated to the Vineland standard scores. RESULTS: A total of 70 fetuses were included. No significant correlation was observed between the Vineland scores and either the supratentorial brain volume, cerebellar volume, or supratentorial brain volume/cerebellar volume ratio in 3D or 2D MR imaging measurements, after correction for multiple comparisons. No differences were found among fetuses with macrocephaly, normocephaly, or microcephaly regarding the median Vineland standard scores. CONCLUSIONS: Provided there is normal brain structure on MR imaging, the developmental milestone achievements in early years are unrelated to 2D and 3D fetal brain MR imaging biometry, in the range of measurements depicted in this study.


Assuntos
Megalencefalia , Microcefalia , Biometria , Encéfalo/diagnóstico por imagem , Estudos de Coortes , Feminino , Feto/diagnóstico por imagem , Idade Gestacional , Humanos , Imageamento por Ressonância Magnética , Microcefalia/diagnóstico por imagem , Gravidez , Ultrassonografia Pré-Natal
3.
PLoS Genet ; 17(7): e1009651, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34197453

RESUMO

Smith-Kingsmore syndrome (SKS) is a rare neurodevelopmental disorder characterized by macrocephaly/megalencephaly, developmental delay, intellectual disability, hypotonia, and seizures. It is caused by dominant missense mutations in MTOR. The pathogenicity of novel variants in MTOR in patients with neurodevelopmental disorders can be difficult to determine and the mechanism by which variants cause disease remains poorly understood. We report 7 patients with SKS with 4 novel MTOR variants and describe their phenotypes. We perform in vitro functional analyses to confirm MTOR activation and interrogate disease mechanisms. We complete structural analyses to understand the 3D properties of pathogenic variants. We examine the accuracy of relative accessible surface area, a quantitative measure of amino acid side-chain accessibility, as a predictor of MTOR variant pathogenicity. We describe novel clinical features of patients with SKS. We confirm MTOR Complex 1 activation and identify MTOR Complex 2 activation as a new potential mechanism of disease in SKS. We find that pathogenic MTOR variants disproportionately cluster in hotspots in the core of the protein, where they disrupt alpha helix packing due to the insertion of bulky amino acid side chains. We find that relative accessible surface area is significantly lower for SKS-associated variants compared to benign variants. We expand the phenotype of SKS and demonstrate that additional pathways of activation may contribute to disease. Incorporating 3D properties of MTOR variants may help in pathogenicity classification. We hope these findings may contribute to improving the precision of care and therapeutic development for individuals with SKS.


Assuntos
Transtornos do Neurodesenvolvimento/genética , Serina-Treonina Quinases TOR/genética , Adulto , Pré-Escolar , Deficiências do Desenvolvimento/genética , Feminino , Humanos , Deficiência Intelectual/genética , Masculino , Megalencefalia/genética , Pessoa de Meia-Idade , Mutação , Mutação de Sentido Incorreto , Transtornos do Neurodesenvolvimento/fisiopatologia , Fenótipo , Serina-Treonina Quinases TOR/metabolismo
4.
Pediatr Clin North Am ; 68(4): 759-773, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34247707

RESUMO

Macrocephaly is commonly encountered in the primary care provider's office. It is defined as an occipitofrontal circumference that is greater than 2 standard deviations above the mean for the child's given age. Macrocephaly is a nonspecific clinical finding that may be benign or require further evaluation. An algorithmic approach is useful for aiding in the clinical decision-making process to determine if further evaluation with neuroimaging is warranted. Abnormal findings may signify a harmful underlying cause, requiring referral to a genetic specialist or neurosurgeon.


Assuntos
Proteção da Criança/estatística & dados numéricos , Megalencefalia/diagnóstico , Megalencefalia/terapia , Atenção Primária à Saúde/organização & administração , Criança , Desenvolvimento Infantil , Humanos , Doenças do Sistema Nervoso/diagnóstico , Doenças do Sistema Nervoso/terapia
5.
Int J Mol Sci ; 22(11)2021 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-34071723

RESUMO

Pathogenic copy number variations (CNVs) contribute to the etiology of neurodevelopmental/neuropsychiatric disorders (NDs). Increased CNV burden has been found to be critically involved in NDs compared with controls in clinical studies. The 1q21.1 CNVs, rare and large chromosomal microduplications and microdeletions, are detected in many patients with NDs. Phenotypes of duplication and deletion appear at the two ends of the spectrum. Microdeletions are predominant in individuals with schizophrenia (SCZ) and microcephaly, whereas microduplications are predominant in individuals with autism spectrum disorder (ASD) and macrocephaly. However, its complexity hinders the discovery of molecular pathways and phenotypic networks. In this review, we summarize the recent genome-wide association studies (GWASs) that have identified candidate genes positively correlated with 1q21.1 CNVs, which are likely to contribute to abnormal phenotypes in carriers. We discuss the clinical data implicated in the 1q21.1 genetic structure that is strongly associated with neurodevelopmental dysfunctions like cognitive impairment and reduced synaptic plasticity. We further present variations reported in the phenotypic severity, genomic penetrance and inheritance.


Assuntos
Anormalidades Múltiplas/genética , Variações do Número de Cópias de DNA/genética , Predisposição Genética para Doença , Megalencefalia/genética , Transtornos Mentais/genética , Transtorno do Espectro Autista/genética , Deleção Cromossômica , Duplicação Cromossômica , Cromossomos Humanos Par 1/genética , Estudo de Associação Genômica Ampla , Humanos , Microcefalia/genética , Doenças Neurodegenerativas/genética , Transtornos do Neurodesenvolvimento/genética , Esquizofrenia/genética
7.
Andrologia ; 53(7): e14100, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33961714

RESUMO

This study reports chromatin status and ICSI outcomes in a case of sperm macrocephaly syndrome(SMS), showing 100% of spermatozoa with abnormal morphology. Percentages of sperm DNA fragmentation for TUNEL (31.7% versus 6.5%), SCSA (33% versus 25%) assays, chromatin maturity tests, CMA3 (58% versus 29%) and aniline blue (63% versus 35%) staining were higher in case sample compared to the fertile sample. Artificial oocyte activation resulted in a similar fertilisation rate between case and control samples (71% versus 66.7%), but the case showed delayed embryo development on day 3 post-insemination. Unlike fertile case, no embryos reached the blastocyst stage. The result of this case study shows that macrocephaly is associated with reduced chromatin maturity and DNA integrity. Although both cases showed a similar chance for fertilisation through artificial chemical activation for only macrocephalic man, the developmental competency is jeopardised in such cases.


Assuntos
Cromatina , Megalencefalia , Fragmentação do DNA , Humanos , Marcação In Situ das Extremidades Cortadas , Masculino , Espermatozoides
8.
Childs Nerv Syst ; 37(8): 2441-2449, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34047857

RESUMO

PURPOSE: We describe our series of 4 patients with megalencephaly-capillary malformation syndrome (MCAP) and review the literature in order to assess the optimal treatment for the associated hydrocephalus. METHODS: We review our institutional series of hydrocephalus associated with MCAP and review the literature, analyzing the causes that could originate the hydrocephalus and the different types of treatments proposed for them. RESULTS: Of our patients treated with ventriculoperitoneal (VP) shunt, one suffered a surgical revision of the shunt and died due to a cranial trauma unrelated to her syndrome or the previous shunt surgery, and the other did not undergo surgical revisions until the end of her follow-up. Our patients treated with endoscopic third ventriculostomy (ETV) have improved their symptomatology and have not suffered of any complications related to the hydrocephalus after the ETV surgery. CONCLUSIONS: We update the treatment of MCAP-associated hydrocephalus and propose ETV as a valid treatment, as it seems a safe procedure with a low rate of complications.


Assuntos
Hidrocefalia , Megalencefalia , Neuroendoscopia , Terceiro Ventrículo , Feminino , Humanos , Hidrocefalia/complicações , Hidrocefalia/diagnóstico por imagem , Lactente , Megalencefalia/complicações , Megalencefalia/diagnóstico por imagem , Megalencefalia/cirurgia , Estudos Retrospectivos , Terceiro Ventrículo/diagnóstico por imagem , Terceiro Ventrículo/cirurgia , Resultado do Tratamento , Derivação Ventriculoperitoneal , Ventriculostomia
9.
AJNR Am J Neuroradiol ; 42(8): 1528-1534, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-33958329

RESUMO

BACKGROUND AND PURPOSE: Ganglionic eminence abnormalities on fetal MR imaging are associated with cerebral malformations. Their presumed genetic basis and associated postnatal outcomes remain largely unknown. We aimed to elucidate these through a multicenter study. MATERIALS AND METHODS: Between January 2010 and June 2020, seven hospitals in 2 countries performing fetal MR imaging examinations identified fetal MR imaging studies demonstrating ganglionic eminence enlargement, cavitation, or both. Cases with no genetic diagnosis, no whole exome sequencing, or no outcome of a liveborn child were excluded. Head size was classified as large (fronto-occipital diameter > 95th centile), small (fronto-occipital diameter <5th centile), or normal. RESULTS: Twenty-two fetuses with ganglionic eminence abnormalities were identified. Of 8 with large heads, 2 were diagnosed with MTOR mutations; 1 with PIK3CA mutation-producing megalencephaly, polymicrogyria, polydactyly, hydrocephalus (MPPH) syndrome; 3 with TSC mutations; 1 with megalencephaly capillary malformation syndrome; and 1 with hemimegalencephaly. Cardiac rhabdomyoma was present prenatally in all cases of TSC; mutation postaxial polydactyly accompanied megalencephaly capillary malformation and MPPH. Of 12 fetuses with small heads, 7 had TUBA1A mutations, 1 had a TUBB3 mutation, 2 had cobblestone lissencephaly postnatally with no genetic diagnosis, 1 had a PDHA1 mutation, and 1 had a fetal akinesia dyskinesia sequence with no pathogenic mutation on trio whole exome sequencing. One of the fetuses with a normal head size had an OPHN1 mutation with postnatal febrile seizures, and the other had peri-Sylvian polymicrogyria, seizures, and severe developmental delay but no explanatory mutation on whole exome sequencing. CONCLUSIONS: Fetal head size and extracranial prenatal sonographic findings can refine the phenotype and facilitate genetic diagnosis when ganglionic eminence abnormality is diagnosed with MR imaging.


Assuntos
Hidrocefalia , Megalencefalia , Polidactilia , Polimicrogiria , Feminino , Feto , Humanos , Polidactilia/diagnóstico por imagem , Polidactilia/genética , Gravidez
10.
Pediatr Radiol ; 51(6): 891-897, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33999235

RESUMO

Enlarged subarachnoid spaces are a common finding in infants and young children imaged for macrocephaly or an enlarging head circumference, and benign enlargement of the subarachnoid spaces is often diagnosed. Infrequently, presumed "spontaneous" subdural hemorrhages or subdural collections might complicate these enlarged subarachnoid spaces. Children with large bilateral subdural collections might also present for imaging with macrocephaly. Each scenario potentially raises concerns for prior injury because subdural hemorrhage is a frequent finding in children with abusive head trauma.


Assuntos
Maus-Tratos Infantis , Traumatismos Craniocerebrais , Megalencefalia , Criança , Maus-Tratos Infantis/diagnóstico , Pré-Escolar , Hematoma Subdural/diagnóstico por imagem , Humanos , Lactente , Megalencefalia/diagnóstico por imagem , Espaço Subaracnóideo
11.
Fetal Diagn Ther ; 48(5): 407-410, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34000720

RESUMO

We present the prenatal imaging and whole exomics sequencing with the newly described Snijders Blok-Campeau macrocephaly syndrome.


Assuntos
Megalencefalia , Diagnóstico Pré-Natal , Feminino , Feto/diagnóstico por imagem , Humanos , Megalencefalia/diagnóstico por imagem , Megalencefalia/genética , Gravidez , Ultrassonografia Pré-Natal , Sequenciamento Completo do Exoma
12.
Clin Dysmorphol ; 30(3): 142-146, 2021 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-34016807

RESUMO

KIAA0753-related skeletal ciliopathy is a recently described recessive disorder causing skeletal dysplasia and overlapping features of certain ciliopathies; Joubert, Jeune and Oro-facial-digital syndromes. We describe a ninth case that expands the phenotype; a 10-year-old girl with rhizomelic short stature (-5.6 SD), macrocephaly, developmental delay, CNS anomalies (thin corpus callosum, bilateral ventriculomegaly), cone-rod dystrophy, nystagmus, mild conductive hearing loss and recurrent chest infections secondary to confirmed ciliary dyskinesia. Testing for FGFR3 achondroplasia-related hotspots and mucopolysaccharidosis were negative. Whole-exome sequencing, aged eight, via skeletal dysplasia panel analysis and subsequent whole-genome sequencing (via the 100,000 genomes project) found no cause. WGS data reanalysis using exomiser uncovered compound heterozygous pathogenic KIAA0753 variants (frameshift and splice site). Further clinical and radiological surveys were consistent with the expected phenotype. We discuss the emerging phenotype of this uncommon disorder. This report details the sixth published case of skeletal dysplasia in all cases of KIAA0753-related disease and the first case to describe a novel c.1830-2A>G splice variant. Our case is the eldest woman reported to date (aged ten years) and the only known case to report associated hearing loss, leg-length discrepancy, pectus carinatum, respiratory ciliary dyskinesia and late-onset (9 years old) neuro-degenerative regression.


Assuntos
Ciliopatias/genética , Proteínas Associadas aos Microtúbulos/genética , Anormalidades Múltiplas/genética , Doenças do Desenvolvimento Ósseo/genética , Criança , Deficiências do Desenvolvimento/genética , Síndrome de Ellis-Van Creveld/genética , Anormalidades do Olho/genética , Feminino , Mutação da Fase de Leitura/genética , Predisposição Genética para Doença/genética , Humanos , Doenças Renais Císticas/genética , Megalencefalia/genética , Proteínas Associadas aos Microtúbulos/metabolismo , Mutação/genética , Síndromes Orofaciodigitais/genética , Linhagem , Sequenciamento Completo do Exoma
13.
J Pediatr ; 236: 301-306, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34023345

RESUMO

Untreated congenital toxoplasmosis remains an important cause of neurologic and ocular disease worldwide. However, congenitally infected infants may not have signs and symptoms their physicians recognize, leading to delayed diagnosis and missed opportunities for treatment. We describe a pair of twins diagnosed with congenital toxoplasmosis at 11 months of age following incidental detection of leukocoria in one twin.


Assuntos
Megalencefalia/etiologia , Distúrbios Pupilares/etiologia , Toxoplasmose Congênita/diagnóstico , Diagnóstico Tardio , Feminino , Humanos , Achados Incidentais , Lactente , Masculino , Gêmeos Dizigóticos
14.
Genet Med ; 23(8): 1484-1491, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-33833411

RESUMO

PURPOSE: Hypomelanosis of Ito (HI) is a skin marker of somatic mosaicism. Mosaic MTOR pathogenic variants have been reported in HI with brain overgrowth. We sought to delineate further the pigmentary skin phenotype and clinical spectrum of neurodevelopmental manifestations of MTOR-related HI. METHODS: From two cohorts totaling 71 patients with pigmentary mosaicism, we identified 14 patients with Blaschko-linear and one with flag-like pigmentation abnormalities, psychomotor impairment or seizures, and a postzygotic MTOR variant in skin. Patient records, including brain magnetic resonance image (MRI) were reviewed. Immunostaining (n = 3) for melanocyte markers and ultrastructural studies (n = 2) were performed on skin biopsies. RESULTS: MTOR variants were present in skin, but absent from blood in half of cases. In a patient (p.[Glu2419Lys] variant), phosphorylation of p70S6K was constitutively increased. In hypopigmented skin of two patients, we found a decrease in stage 4 melanosomes in melanocytes and keratinocytes. Most patients (80%) had macrocephaly or (hemi)megalencephaly on MRI. CONCLUSION: MTOR-related HI is a recognizable neurocutaneous phenotype of patterned dyspigmentation, epilepsy, intellectual deficiency, and brain overgrowth, and a distinct subtype of hypomelanosis related to somatic mosaicism. Hypopigmentation may be due to a defect in melanogenesis, through mTORC1 activation, similar to hypochromic patches in tuberous sclerosis complex.


Assuntos
Hipopigmentação , Megalencefalia , Humanos , Hipopigmentação/genética , Alvo Mecanístico do Complexo 1 de Rapamicina/genética , Mosaicismo , Fenótipo , Serina-Treonina Quinases TOR/genética
15.
Genes (Basel) ; 12(3)2021 03 02.
Artigo em Inglês | MEDLINE | ID: mdl-33801456

RESUMO

The phosphatase and tensin homolog (PTEN) gene is a tumor-suppressor gene located on 10q22-23. Since the introduction of molecular genetics in prenatal diagnostics, various birth defects associated with gene mutations have been diagnosed. However, no reports on fetal cases related to PTEN mutation have been found, so far. We encountered a rare case of fetal PTEN mutation. Fetal macrocephaly was noted at 16 weeks. At 18 and 20 weeks, neurosonography revealed megalencephaly with an asymmetrical structure and multifocal polygyria. The head circumference (HC) was +6.2 SD at 18 weeks and +8.1 SD at 20 weeks. The parents opted for pregnancy termination, and the male fetus was delivered at 21 weeks, with HC +9.3 SD. Single-nucleotide polymorphism (SNP) array for amniotic cells showed paternal uniparental disomy (UPD) 10q mosaicism, and the mosaic ratio was calculated as 56% from B-allele frequency. Exome sequencing revealed the pathogenic PTEN mutation with mosaicism. The heterozygous PTEN mutation may not cause early manifestations from the fetal period, and an abnormal phenotype may appear after birth. This may be the reason why fetal defects associated with PTEN mutation are not detected. Since this case had homozygous and heterozygous mutations, survival was possible, exhibiting an incredibly huge head with cortical dysplasia from early pregnancy.


Assuntos
Malformações do Desenvolvimento Cortical/diagnóstico por imagem , Megalencefalia/diagnóstico por imagem , PTEN Fosfo-Hidrolase/genética , Trissomia/genética , Dissomia Uniparental/genética , Aborto Induzido , Cromossomos Humanos Par 10/genética , Feminino , Humanos , Masculino , Malformações do Desenvolvimento Cortical/genética , Megalencefalia/genética , Mosaicismo , Mutação , Herança Paterna , Polimorfismo de Nucleotídeo Único , Gravidez , Segundo Trimestre da Gravidez
16.
Eur J Med Genet ; 64(5): 104199, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33746039

RESUMO

Temple syndrome (TS14) can be originated by maternal uniparental disomy (UPD(14)mat), paternal deletion, or epimutation, leading to disturbances in 14q32.2 imprinted region. The most frequent phenotypic manifestations are prenatal and postnatal growth failure, hypotonia, developmental delay, small hands/feet, precocious puberty, and truncal obesity. However, the diagnosis can be challenging due to the clinical overlap with other imprinting disorders such as Silver-Russell or Prader-Willi syndromes. Although rare, TS14 has been also reported in patients with concomitant UPD(14)mat and mosaic trisomy 14. In the present report, the clinical and genetic profiles of two new patients with TS14 are described. SNParray and MS-MLPA, allowed the determination of segmental UPD(14)mat and the hypomethylation of MEG3 gene. Additionally, in one of our patients we also observed by cytogenetics a small supernumerary marker chromosome that led to partial trisomy 14 in mosaic. Only few patients with concomitant UPD(14)mat and mosaic partial trisomy 14 have been reported. Our patients share cardinal TS14 phenotypic features that are associated to the genetic abnormalities detected; however, we also observed some clinical features such as fatty liver disease that had not previously been reported as part of this syndrome. The detailed clinical, cytogenetical and molecular description of these two new patients, contributes to a more accurately delineation of this syndrome.


Assuntos
Cromossomos Humanos Par 14/genética , Deficiências do Desenvolvimento/genética , Hepatopatias/genética , Megalencefalia/genética , Dissomia Uniparental , Adolescente , Criança , Deficiências do Desenvolvimento/patologia , Humanos , Hepatopatias/patologia , Masculino , Megalencefalia/patologia , Mosaicismo , Síndrome
18.
Sci Rep ; 11(1): 2908, 2021 02 03.
Artigo em Inglês | MEDLINE | ID: mdl-33536524

RESUMO

Microcephaly and macrocephaly can be considered both cranial growth defects and clinical symptoms. There are two assessment criteria: one applied in dysmorphology and another conventionally used in clinical practice. The determination of which definition or under which paradigm the terminology should be applied can vary on a daily basis and from case to case as necessity dictates, as can defining the relationship between microcephaly or macrocephaly and syndromes or diseases associated with neurodysfunction. Thus, there is a need for standardization of the definition of microcephaly and macrocephaly. This study was designed to investigate associations between abnormal cranial development (head size) and diseases or syndromes linked to neurodysfunction based on essential data collected upon admission of patients to the Neurological Rehabilitation Ward for Children and Adolescents in Poland. The retrospective analysis involved 327 children and adolescents with medical conditions associated with neurodysfunction. Two assessment criteria were applied to identify subgroups of patients with microcephaly, normal head size, and macrocephaly: one system commonly used in clinical practice and another applied in dysmorphology. Based on the results, children and adolescents with syndromes or diseases associated with neurodysfunction present abnormal cranial development (head size), and microcephaly rarely co-occurs with neuromuscular disease. Macrocephaly frequently co-occurs with neural tube defects or neuromuscular diseases and rarely with cerebral palsy (p < 0.05); microcephaly frequently co-occurs with epilepsy and hypothyroidism (p < 0.001). Traditional classification facilitates the identification of a greater number of relationships and is therefore recommended for use in daily practice. There is a need to standardize the definition of microcephaly and macrocephaly and to include them in 'Human Phenotype Ontology' terms.


Assuntos
Cefalometria/normas , Megalencefalia/diagnóstico , Microcefalia/diagnóstico , Doenças do Sistema Nervoso/complicações , Crânio/crescimento & desenvolvimento , Adolescente , Desenvolvimento do Adolescente/fisiologia , Criança , Desenvolvimento Infantil/fisiologia , Pré-Escolar , Feminino , Humanos , Masculino , Megalencefalia/etiologia , Megalencefalia/fisiopatologia , Microcefalia/etiologia , Microcefalia/fisiopatologia , Doenças do Sistema Nervoso/fisiopatologia , Polônia , Estudos Retrospectivos , Síndrome
19.
Clin Dysmorphol ; 30(3): 121-124, 2021 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-33605605

RESUMO

Homozygous or compound heterozygous mutations in STRADA cause polyhydramnios, megalencephaly and symptomatic epilepsy syndrome (PMSE), with additional features of distinctive facial traits and severe developmental delay or intellectual disability. This syndrome was first defined in 16 Old Order Mennonite patients, carrying a homozygous STRADA deletion of exon 9-13. Five additional PMSE patients have been reported since, each of them with loss-of-function variants. We report a female patient with the typical clinical features of PMSE, homozygous for a novel STRADA missense mutation c.792T>A (p.Ser264Arg) in exon 10. This finding contributes to the further delineation of the phenotype of PMSE.


Assuntos
Proteínas Adaptadoras de Transporte Vesicular/genética , Proteínas Adaptadoras de Transporte Vesicular/metabolismo , Síndromes Epilépticas/genética , Criança , Deficiências do Desenvolvimento/genética , Epilepsia Generalizada/genética , Feminino , Homozigoto , Humanos , Deficiência Intelectual/genética , Megalencefalia/genética , Mutação de Sentido Incorreto/genética , Fenótipo , Poli-Hidrâmnios/genética , Gravidez
20.
Eur J Med Genet ; 64(4): 104166, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33571694

RESUMO

CHD3-related syndrome, also known as Snijders Blok-Campeau syndrome, is a rare developmental disorder described in 2018, caused by de novo pathogenic variants in the CHD3 gene. This syndrome is characterized by global developmental delay, speech delay, intellectual disability, hypotonia and behavioral disorders including autism spectrum disorder (ASD). Typical dysmorphic features include macrocephaly, hypertelorism, enophthalmia, sparse eyebrows, bulging forehead, midface hypoplasia, prominent nose and pointed chin. To our knowledge, there have been no other clinical descriptions of patients since the initial publication. We report the clinical description of a 21-year-old patient harboring a pathogenic de novo variant in CHD3. We reviewed the clinical features of the 35 previously reported patients. Main features were severe intellectual disability, dysmorphic facies, macrocephaly, cryptorchidism, pectus carinatum, severe ophthalmologic abnormalities and behavioral disorders including ASD, and a frank happy demeanor. Hypersociability, which was a noticeable clinical feature in our case, despite ASD, is an uncommon behavioral feature in syndromic intellectual disabilities. Our report supports hypersociability as a suggestive feature of CHD3-related syndrome along with developmental delay, macrocephaly and a dysmorphic facies.


Assuntos
Anormalidades Craniofaciais/genética , DNA Helicases/genética , Deficiências do Desenvolvimento/genética , Megalencefalia/genética , Complexo Mi-2 de Remodelação de Nucleossomo e Desacetilase/genética , Comportamento Social , Anormalidades Craniofaciais/patologia , Deficiências do Desenvolvimento/patologia , Humanos , Masculino , Megalencefalia/patologia , Mutação , Síndrome , Adulto Jovem
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