Holoprosencephaly in Patau Syndrome / Holoprosencefalia na Síndrome de Patau

ABSTRACT 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.

RESUMO Objetivo: Avaliar sinais radiológicos (gestacionais e perinatais) e neonatais de paciente com síndrome de Patau e holoprosencefalia semilobar, assim como relatar a associação de ambas as patologias. Descrição do caso: Trata-se de um relato de recém-nascido do sexo feminino a termo, que apresentou trissomia do cromossomo 13 e holoprosencefalia semilobar, com fusão talâmica e ventrículo cerebral único, além de várias outras alterações que pioraram o prognóstico da paciente. Comentários: A trissomia do cromossomo 13 é um defeito genético que caracteriza um conjunto de sintomas que compõem a Síndrome de Patau. Nesta síndrome, é comum o acometimento cardiovascular, urogenital, do sistema nervoso central, da estrutura facial e da capacidade intelectual, além de falhas na formação dos membros, como diminuição no comprimento do úmero, fêmur, polidactilia, hipotelorismo e baixa implantação das orelhas. Estima-se, no entanto, que a holoprosencefalia apresente-se nesse grupo de malformações congênitas apenas em 24 a 45% dos casos.

CEP135 associated primary microcephaly-A rare presentation in early second trimester.

Primary microcephaly (MCPH) is a rare neurogenic disorder with most cases being inherited in an autosomal recessive pattern. The present report is of a case of second gravid patient with recurrent fetal microcephaly with agenesis of corpus callosum, cerebellar hypoplasia and ventriculomegaly. Maternal TORCH profile and amniotic fluid chromosomal microarray were normal. Following the termination of pregnancy, the autopsy evaluation has shown additional findings of evolving craniosynostosis, and semilobar holoprosencephaly. Whole exome sequencing done on fetal DNA from amniotic fluid, revealed a pathogenic compound heterozygous variant (NM_025009.5) c.2863C>T (p.Arg955Ter) in exon 22 and c.1372_1375del (p.Lys459SerfsTer2) in exon 11 of CEP135 gene: known to cause primary microcephaly-8; and both partners in the couple are heterozygous carriers for the same. With the identification of MCPH genes and with the availability of next-generation sequencing (NGS) based exome sequencing, a definitive prenatal diagnosis of primary microcephaly and also appropriate genetic counselling for the couple has become possible.

Holoprosencefalia semilobar y malformaciones asociadas: reporte de caso y algunas consideraciones / Semilobar holoprosencephaly and associated malformations: case report and some considerations

RESUMEN: El defecto más común del prosencéfalo es la holoprosencefalia (HPE), caracterizada por ausencia en la división del prosencéfalo. La holoprosencefalia tiene una prevalencia de 1/10.000 en recién nacidos; la ciclopía de 1/100.000 nacidos y la agnatia asociada a holoprosencefalia de 0,8 a 10 %. El objetivo fue describir las características morfológicas e histopatológicas de un feto humano con holoprosencefalia y sus malformaciones asociadas. Se estudió un feto masculino. Se le realizó microdisección bajo el estereomicroscopio, toma de microfotografías con cámara AxioCam y software AxioVision 4.8, y estudio histopatológico. La edad gestacional estimada fue de 12,4-13,2 semanas, encontrándose como hallazgos la HPE semilobar asociada a ciclopía, esbozo oral hipoplásico sin apertura oral, cubierta por una membrana y ausencia de labios. El estudio histopatológico reportó: ojo con lente, retina y córnea únicos; en la cara, probóscide con cartílago tubular en formación asociado a mesénquima y cubierta muscular esquelética, y cavidad oral pequeña, circunscrita por mandíbula hipoplásica conformada por cartílago. Se revisa la literatura y se reafirma la necesidad de estudio multidisciplinario de esta patología para mejorar su comprensión.

SUMMARY: The most common defect of the forebrain is holoprosencephaly (HPE), characterized by absence in the forebrain division. Holoprosencephaly has a prevalence of 1 / 10,000 in newborns; the cyclopia of 1 / 100,000 births and the agnathia, in a series of cases of holoprosencephaly ranges from 0.8 to 10 %. The objective was the description of the morphological and histopathological characteristics of fetus with holoprosencephaly and its associated malformations. A male fetus was studied. Microdissection was performed under the stereomicroscope, taking microphotographs with AxioCam camera and AxioVision 4.8 software, and histopathological study. The estimated gestational age was 12.4-13.2 weeks, the findings were semilobar HPE, associated with cyclopia, hypoplastic oral outline without buccal opening, covered by a membrane and lips absence. The histopathological study reported: eye with lens, retina and cornea only; in the face, proboscis with tubular cartilage in formation associated with mesenchyme and musculoskeletal sheath, and small oral cavity, delimited by hypoplastic mandible conformed by cartilage. The literature is reviewed and reaffirmed the need for multidisciplinary studies of this disease to improve their understanding.

Digynic triploidy in a fetus presenting with semilobar holoprosencephaly.

OBJECTIVE: We present digynic triploidy in a fetus with semilobar holoprosencephaly (HPE). CASE REPORT: A 32-year-old, gravid 1, para 0, woman underwent prenatal ultrasound examination at 12 weeks of gestation, and the ultrasound showed relative macrocephaly, a small non-cystic placenta, and a fetus with absent nasal bone and semilobar HPE. The pregnancy was terminated subsequently, and a 50-g fetus was delivered with a relatively enlarged head and premaxillary agenesis. The placenta was small and non-cystic. Postnatal cytogenetic analysis of the umbilical cord revealed a karyotype of 69, XXX. Postnatal DNA marker analysis using quantitative fluorescent polymerase chain reaction assays and the polymorphic short tandem repeat markers for chromosome 18 and 20 on the placental tissues showed a diallelic pattern with a dosage of 1:2 (paternal allele to maternal allele ratio), indicating a maternal origin of the triploidy. CONCLUSION: Fetuses with digynic triploidy may present relative macrocephaly, semilobar HPE and a small placenta on prenatal ultrasound.

Semilobar holoprosencephaly in a 12-month-old baby boy born to a primigravida patient with type 1 diabetes mellitus: a case report.

BACKGROUND: Holoprosencephaly is a rare spectrum of cephalic disorders resulting from a failure or incomplete division of the embryonic forebrain into distinct cerebral hemispheres. It is the most common brain malformation with an incidence of 1:250 during embryogenesis; however, owing to the associated high rates of spontaneous abortion the incidence is 1:16,000 among live deliveries. Pathogenesis of holoprosencephaly is complex and heterogeneous involving genetic abnormalities, teratogenic exposures, and syndromic associations. Among the teratogenic exposures, maternal diabetes is a well-established risk factor associated with a 200-fold increased incidence of holoprosencephaly. CASE PRESENTATION: We report a case of a delayed diagnosis of semilobar holoprosencephaly in a 12-month-old baby boy of African descent who presented to us with a history of global developmental delay, erratic sleep patterns, and poor weight gain. He was born to a type 1 diabetes mellitus mother at 39+ weeks by emergency cesarean section due to fetal distress and breech presentation. The baby weighed 2315 g and had Apgar scores of 6/10 and 8/10 at 1 and 5 minutes respectively. A physical examination done at 12 months of age revealed a small-for-age child with a developmental age of 2 months. He had normal facies but a neurological examination revealed hypotonia in all four limbs. The rest of systemic examination was unremarkable. Hematological and biochemical investigations revealed normal findings except for iron deficiency anemia. The child also underwent magnetic resonance imaging of his brain which revealed distinctive features of semilobar holoprosencephaly. He was treated for iron deficiency anemia with Hemovit syrup (ferric ammonium citrate, folic acid, pyridoxine hydrochloride, cyanocobalamin, and zinc sulfate) 10 ml thrice daily, ferrous sulfate 10 mg once daily, folic acid 1 mg once daily, and multivitamin syrup 5 ml once daily. Furthermore, nutritional and genetic counseling was offered to his parents. CONCLUSIONS: In conclusion, although rare, holoprosencephaly is the commonest structural anomaly of the brain with a complex and multifactorial etiopathogenesis. It is prudent to diagnose it prenatally, classify its severity, and forge its prognosis so that parents are counseled early enough to make informed decisions especially where termination of pregnancy may be implicated.

Two patients with small chromosome 22q11.21 alterations and central nervous system abnormalities.

BACKGROUND: Central nervous system features have been rarely described to be associated with the small deletion or duplication of chromosome 22q11.21. CASE PRESENTATION: We report two patients with chromosome 22q11.21 alterations and central nervous system abnormalities. Features described include semilobar holoprosencephaly in the patient with the small deletion and Chiari I malformation in the patient with the small duplication. CONCLUSIONS: This report will aid in the characterization of the clinical significance of interstitial duplications and deletions on the long-arm of chromosome 22. Areas of future research would benefit from additional analysis of the described regions with inclusion of the phenotypic findings described in this case report to provide additional insight into the pathogenicity of the described alterations.

Semilobar Holoprosencephaly with Neurogenic Hypernatraemia: Two new cases.

Holoprosencephaly (HPE) is a developmental defect of the embryonic forebrain and midface. It is due to the non-cleavage of the embryonic forebrain into two cerebral hemispheres and the incomplete development of the paramedian structures. The overall prevalence is 1.31 per 10,000 births. The aetiology could be genetic, environmental, or both. HPE is classified into alobar, semilobar, and lobar subtypes based on the degree of separation of the cerebral hemispheres. We report two new cases of semilobar HPE with neurogenic hypernatraemia. Lack of thirst and hypodypsia associated with chronic hypernatraemia in patients with HPE is highly suggestive of neurogenic hypernatraemia. Early identification of neurogenic hypernatraemia is important as it improves with forced fluid therapy and does not require any medication.