RESUMO
OBJECTIVE: To evaluate radiological (gestational and perinatal) and neonatal signs of patients with Patau syndrome and semilobar holoprosencephaly, as well as to report the association of both pathologies. CASE DESCRIPTION: This case report is about a female infant, born at term with trisomy of the chromosome 13 and semilobar holoprosencephaly, with thalamic fusion and a single cerebral ventricle, in addition to several other changes that worsened the patient's prognosis. COMMENTS: Chromosome 13 trisomy is a genetic alteration that leads to the symptoms that determines Patau syndrome. In this syndrome, cardiovascular, urogenital, central nervous system, facial structure and intellectual impairment are common, in addition to problems in limb formation, such as decreased humerus and femur length, polydactyly, hypotelorism and low ear implantation. It is estimated, however, that holoprosencephaly is present in only 24 to 45% of the patients with trisomy 13.
Assuntos
Holoprosencefalia , Polidactilia , Recém-Nascido , Gravidez , Lactente , Humanos , Feminino , Holoprosencefalia/diagnóstico , Holoprosencefalia/diagnóstico por imagem , Síndrome da Trissomia do Cromossomo 13/complicações , Síndrome da Trissomia do Cromossomo 13/diagnóstico , Trissomia , Polidactilia/complicações , Polidactilia/diagnóstico , Polidactilia/genética , Mutação , Cromossomos Humanos Par 13RESUMO
Holoprosencephaly is the most common brain malformation in humans and it is a complex genetic disorder. We report on a patient with holoprosencephaly caused by a rare ZIC2 mutation presenting a bifid nose associated with a nasal fistula and an epidermal cyst, besides hypernatremia. The patient was a 1 year and 4 months old girl that developed an important neuropsychomotor delay. Currently, she uses a wheelchair to move around and only emits sounds. Computed tomography (CT) scan revealed a semilobar holoprosencephaly and a Dandy-Walker variant. Head magnetic resonance imaging also disclosed corpus callosum agenesis and prefrontal subarachnoid space enlargement. On physical examination at 1 year and 4 months of age, we verified growth retardation, microcephaly, bilateral epicantic fold, upslanting palpebral fissures, bifid nose, and limbs spasticity secondary to hypertonia. Later, she began to present hypernatremia; however, its precise cause was not identified. At 6 years and 10 months of age, a nasal fistula was suspected. Facial CT scan showed an epidermal cyst at cartilaginous portion of the nasal septum. High resolution GTG-Banding karyotype was normal. However, molecular analysis through direct sequencing technique showed a mutation at regulatory region of the ZIC2 gene: c.1599*954T > A, a genetic variation previously described only in a Brazilian patient. Our patient presented findings still not reported in literature among patients with holoprosencephaly, including those with ZIC2 mutations. Thus, the spectrum of abnormalities associated to ZIC2 mutations may be broader and include other defects as those observed in our patient.
Assuntos
Cisto Epidérmico/genética , Holoprosencefalia/genética , Hipernatremia/genética , Proteínas Nucleares/genética , Mutação Puntual , Fístula do Sistema Respiratório/genética , Fatores de Transcrição/genética , Encéfalo/anormalidades , Encéfalo/diagnóstico por imagem , Cisto Epidérmico/diagnóstico , Fácies , Feminino , Holoprosencefalia/diagnóstico , Humanos , Hipernatremia/diagnóstico , Lactente , Imageamento por Ressonância Magnética , Fenótipo , Fístula do Sistema Respiratório/diagnóstico , Síndrome , Tomografia Computadorizada por Raios XRESUMO
Here we report on a Brazilian child who presented semilobar holoprosencephaly, frontonasal encephaloceles and bilateral cleft lip and palate. Malformations also included agenesis of the corpus callosum, abnormal cortical gyres, dilation of the aqueduct, bilateral endolymphatic sac, bilateral cystic cocci-vestibular malformation, and a cribriform defect. The 3D TC craniofacial images showed abnormal frontonasal transition region, with a bone bifurcation, and partial agenesis of nasal bone. The trunk and upper and lower limbs were normal. To our knowledge, this rare association of holoprocensephaly with frontonaso-orbital encephaloceles without limb anomalies has never been reported before. Karyotype was normal. SNP-array showed no copy-number alterations but revealed 25% of regions of homozygosity (ROH) with normal copy number, indicating a high coefficient of inbreeding, which significantly increases the risk for an autosomal recessive disorder. Whole exome sequencing analysis did not reveal any pathogenic or likely pathogenic variants. We discuss the possible influence of two variants of uncertain significance found within the patient's ROHs. First, a missense p.(Gly394Ser) in PCSK9, a gene involved in the regulation of plasma low-density lipoprotein cholesterol. Second, an inframe duplication p.(Ala75_Ala81dup) in SP8, a zinc-finger transcription factor that regulates signaling centers during craniofacial development. Further studies and/or the identification of other patients with a similar phenotype will help elucidate the genetic etiology of this complex case.
Assuntos
Fenda Labial/diagnóstico , Fenda Labial/genética , Fissura Palatina/diagnóstico , Fissura Palatina/genética , Encefalocele/diagnóstico , Encefalocele/genética , Holoprosencefalia/diagnóstico , Holoprosencefalia/genética , Anormalidades Múltiplas/diagnóstico , Anormalidades Múltiplas/genética , Encéfalo/anormalidades , Encéfalo/diagnóstico por imagem , Mapeamento Cromossômico , Estudos de Associação Genética , Predisposição Genética para Doença , Homozigoto , Humanos , Imageamento Tridimensional , Imageamento por Ressonância Magnética , Masculino , Fenótipo , Polimorfismo de Nucleotídeo Único , Síndrome , Tomografia Computadorizada por Raios X , Sequenciamento do ExomaRESUMO
Reportamos un neonato masculino con defectos de línea media, cardiopatía congénita y polidactilia, características sugestivas de trisomía 13. Sin embargo, el reporte de cariotipo fue normal. Por hallazgos clínicos, el diagnóstico final probable fue pseudotrisomía 13. Aunque el pronóstico de ambas condiciones es pobre, los estudios genéticos siempre son necesarios para establecer una adecuada asesoría genética. Si bien hay síndromes con presentación similar, como el de Meckel, el de Smith-Lemli- Opitz, el de Pallister-Hall y el hidroletalus, se puede realizar una aproximación diagnóstica basada en los antecedentes perinatales, el peso al nacer, el tiempo de supervivencia y algunos rasgos característicos de cada síndrome. Además, pueden existir, en algunos países, limitaciones para realizar estudios genéticos, por lo que los criterios clínicos pueden ser relevantes.
We report a male infant with midline defects, congenital heart disease and polydactyly, features suggestive of trisomy 13. However, the report of the karyotype was normal. By clinical findings the final diagnosis was likely to be Pseudotrisomy 13. Although the prognosis is poor in both conditions, the genetic study is always necessary to establish an adequate genetic counseling. Although there are syndromes with similar presentation as Meckel syndrome, Smith-Lemli-Opitz syndrome, Pallister-Hall syndrome and hydrolethalus, it is possible to make a diagnostic approach based on the perinatal history, birth weight, survival time, and some characteristics of each syndrome. However, limitations may exist to perform genetic studies in some countries, therefore the clinical criteria may be relevant.
Assuntos
Humanos , Masculino , Recém-Nascido , Trissomia/diagnóstico , Cromossomos Humanos Par 13 , Macrossomia Fetal/diagnóstico , Deformidades Congênitas da Mão/diagnóstico , Holoprosencefalia/diagnóstico , Fenda Labial/diagnóstico , Fissura Palatina/diagnóstico , Polidactilia/diagnósticoRESUMO
We report a male infant with midline defects, congenital heart disease and polydactyly, features suggestive of trisomy 13. However, the report of the karyotype was normal. By clinical findings the final diagnosis was likely to be Pseudotrisomy 13. Although the prognosis is poor in both conditions, the genetic study is always necessary to establish an adequate genetic counseling. Although there are syndromes with similar presentation as Meckel syndrome, Smith-Lemli-Opitz syndrome, Pallister-Hall syndrome and hydrolethalus, it is possible to make a diagnostic approach based on the perinatal history, birth weight, survival time, and some characteristics of each syndrome. However, limitations may exist to perform genetic studies in some countries, therefore the clinical criteria may be relevant.
Assuntos
Fenda Labial/diagnóstico , Fissura Palatina/diagnóstico , Macrossomia Fetal/diagnóstico , Deformidades Congênitas da Mão/diagnóstico , Holoprosencefalia/diagnóstico , Polidactilia/diagnóstico , Trissomia/diagnóstico , Cromossomos Humanos Par 13 , Humanos , Recém-Nascido , MasculinoRESUMO
A severe mandibular hypoplasia and microstomy with intraoral anomalies including hypoglossia, fused gums, persistence of buccopharyngeal membrane, and laryngeal hypoplasia were noted in a female newborn with the dysgnathia complex (DC). Additionally, our proposita also presented natal teeth as a probably new finding. These clinical manifestations overlapped with those of the fourth report of hypomandibular faciocranial syndrome (HFS) (31), and given that both lack for craniosynostosis (pathognomonic of HFS), we considered that both represent a subtype of DC proposed as DC sine holoprosencephaly nor synotia (DCSHS). Differential characteristics between the DCSHS, the HFS, and the DC with holoprosencephaly sine synotia are reviewed and additionally, we discussed some aspects about the nosology of the DC.
Assuntos
Anormalidades Múltiplas/diagnóstico , Holoprosencefalia/diagnóstico , Anormalidades Maxilomandibulares/diagnóstico , Craniossinostoses/complicações , Craniossinostoses/diagnóstico , Evolução Fatal , Feminino , Cabeça/diagnóstico por imagem , Holoprosencefalia/complicações , Humanos , Imageamento Tridimensional , Recém-Nascido , Anormalidades Maxilomandibulares/complicações , Mandíbula/anormalidades , Dentes Natais , Tomografia Computadorizada por Raios X/métodosRESUMO
Here we report on a Brazilian female patient with the clinical manifestations of the holoprosencephaly-like phenotype who also presented with a retroocular granuloma diagnosed as Langerhans cell histiocytosis in early infancy. Mutation analysis showed a missense mutation (G316D) in the exon 2 of SIX3 gene, which was predicted as damaged by the PolyPhen program. We discuss the clinical and genetic aspects of this unusual case.
Assuntos
Proteínas do Olho/genética , Heterozigoto , Histiocitose de Células de Langerhans/complicações , Histiocitose de Células de Langerhans/genética , Holoprosencefalia/complicações , Holoprosencefalia/genética , Proteínas de Homeodomínio/genética , Mutação de Sentido Incorreto/genética , Proteínas do Tecido Nervoso/genética , Adulto , Substituição de Aminoácidos/genética , Brasil , Feminino , Histiocitose de Células de Langerhans/diagnóstico , Holoprosencefalia/diagnóstico , Humanos , Imageamento por Ressonância Magnética , Fenótipo , Proteína Homeobox SIX3RESUMO
Here we report on the clinical and genetic data for a large sample of Brazilian patients studied at the Hospital de Reabilitação de Anomalas Craniofaciais-Universidade de São Paulo (HRAC-USP) who presented with either the classic holoprosencephaly or the holoprosencephaly-like (HPE-L) phenotype. The sample included patients without detected mutations in some HPE determinant genes such as SHH, GLI2, SIX3, TGIF, and PTCH, as well as the photographic documentation of the previously reported patients in our Center. The HPE-L phenotype has been also called of HPE "minor forms" or "microforms." The variable phenotype, the challenge of genetic counseling, and the similarities to patients with isolated cleft lip/palate are discussed.
Assuntos
Face , Holoprosencefalia/classificação , Holoprosencefalia/diagnóstico , Brasil , Anormalidades Craniofaciais/diagnóstico , Anormalidades Craniofaciais/etiologia , Análise Mutacional de DNA , Face/anormalidades , Holoprosencefalia/complicações , Holoprosencefalia/genética , Hospitais , Humanos , FenótipoRESUMO
Amplio espectro de anormalidades del desarrollo intracraneano y de la región media de la cara, producido por una división incompleta o inexistente del prosencéfalo (lóbulo frontal del embrión) en los hemisferios cerebrales laterales. Se describen su embriología, incidencia, etiología, formas de presentación, malformaciones asociadas, diagnóstico prenatal, y diagnóstico diferencial.