A child with cat-eye syndrome and oculo-auriculo-vertebral spectrum phenotype: A discussion around molecular cytogenetic findings.

Cat eye syndrome (CES) is a rare chromosomal disorder that may be evident at birth. A small supernumerary chromosome is present, frequently has 2 centromeres, is bisatellited, and represents an inv dup(22)(q11) in those affected. It's known that the 22q11 region is associated with disorders involving higher and lower gene dosages. Conditions such as CES, 22q11 microduplication syndrome (Dup22q11) and oculoauriculovertebral spectrum phenotype (OAVS) may share genes belonging to this same region, which is known to have a predisposition to chromosomal rearrangements. The conditions, besides being related to chromosome 22, also share similar phenotypes. Here we have added a molecular evaluation update and results found of the first patient described with CES and OAVS phenotype, trying to explain the potential mechanism involved in the occurrence of this association.

Population-based prevalence surveys during the Covid-19 pandemic: A systematic review.

Population-based prevalence surveys of Covid-19 contribute to establish the burden of infection, the role of asymptomatic and mild infections in transmission, and allow more precise decisions about reopen policies. We performed a systematic review to evaluate qualitative aspects of these studies, assessing their reliability and compiling practices that can influence the methodological quality. We searched MEDLINE, EMBASE, bioRxiv and medRxiv, and included cross-sectional studies using molecular and/or serological tests to estimate the prevalence of Covid-19 in the general population. Survey quality was assessed using the Joanna Briggs Institute Critical Appraisal Checklist for Prevalence Studies. A correspondence analysis correlated methodological parameters of each study to identify patterns related to higher, intermediate and lower risks of bias. The available data described 37 surveys from 19 countries. The majority were from Europe and America, used antibody testing, and reached highly heterogeneous sample sizes and prevalence estimates. Minority communities were disproportionately affected by Covid-19. Important risk of bias was detected in four domains: sample size, data analysis with sufficient coverage, measurements in standard way and response rate. The correspondence analysis showed few consistent patterns for high risk of bias. Intermediate risk of bias was related to American and European studies, municipal and regional initiatives, blood samples and prevalence >1%. Low risk of bias was related to Asian studies, nationwide initiatives, reverse-transcriptase polymerase chain reaction tests and prevalence <1%. We identified methodological standards applied worldwide in Covid-19 prevalence surveys, which may assist researchers with the planning, execution and reporting of future population-based surveys.

Mismatch negativity in children with complaints of learning difficulties / Mismatch Negativity en niños con quejas de dificultades de aprendizaje

INTRODUCTION: Mismatch Negativity (MMN) is an electrophysiological measure of hearing that reflects the skills of auditory discrimination and central auditory processing. OBJECTIVE: To analyze MMN results in children with complaints of learning difficulties and to compare the results with children without complaints of learning difficulties. MATERIALS AND METHODS: Cross-sectional and comparative study. The sample consisted of 105 male and female children, aged between 8 and 11 years and 11 months, 3rd to 5th graders at Elementary School. The study group consisted of 35 children with learning difficulties and the control group, of 70 children without complaints. All children underwent pure-tone threshold audiometry (PTTA), vocal audiometry, acoustic immittance measurements and Mismatch Negativity (MMN) evaluations. RESULTS: The mean latency of MMN was 213.3ms in the right ear and 215.2ms in the left in the study group, and 169.3ms in the right ear and 170.4ms in the left in the control group. The mean MMN latency was significantly higher in the study group compared to the control group (p<.001). The mean amplitude of MMN in the study group was 5.76μV in the right ear and 5.62μV in the left, while in the control it was 5.01μV in the right ear and 5.22μV in the left. CONCLUSIONS: In the study sample, children with complaints of learning difficulties had significantly higher mean significances than those without the same complaints

ANTECEDENTES Y OBJETIVO: La Mismatch Negativity (MMN) es una medida electrofisiológica de la audición que refleja las habilidades de discriminación auditiva y el procesamiento auditivo central. El objetivo de este estudio fue analizar los resultados de la MMN en los niños con quejas de dificultades de aprendizaje, y comparar los resultados con niños sin quejas de dificultades de aprendizaje. MATERIALES Y MÉTODOS: Estudio transversal y comparativo. La muestra fue constituida por 105 niños de ambos sexos, con edad comprendidas entre 8 y 11 años y 11 meses, 3.ª a 5.ª series de la enseñanza fundamental. El grupo de estudio fue constituido por 35 niños con dificultades de aprendizaje y el grupo control, de 70 niños sin quejas. Todos los niños fueron sometidos a la audiometría tonal liminar (PTTA), a la audiometría vocal, a las medidas de imitancia acústica y a la MMN. RESULTADOS: La latencia media de la MMN fue de 213,3ms en el oído derecho y 215,2ms en el izquierdo en el grupo de estudio, y 169,3ms en el oído derecho y 170,4ms en el izquierdo en el grupo control. La latencia media de la MMN fue significativamente mayor en el grupo de estudio en comparación con el grupo control (p < 0,001). La amplitud media de la MMN en el grupo de estudio fue de 5,76μV en el oído derecho y de 5,62μV en el oído izquierdo, mientras que en el control fue de 5,01μV en el oído derecho y 5,22μV en el oído izquierdo. CONCLUSIONES: En la muestra estudiada, los niños con quejas de dificultades de aprendizaje tuvieron significados significativamente mayores que aquellas sin las mismas quejas

Nasal fistula, epidermal cyst and hypernatremia in a girl presenting holoprosencephaly due to a rare ZIC2 point mutation.

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.

Interstitial deletion of 7q31.32 → q33 secondary to a paracentric inversion of a maternal chromosome 7.

Carriers of paracentric inversions (PAIs) are usually asymptomatic. However, such inversions may lead to the formation of recombinant gametes and then to an abnormal gestation. Here we report a girl with a 7q31.32 → q33 deletion secondary to a maternal PAI of chromosome 7. This finding was confirmed through FISH and whole-genome array-CGH analyses. The deficiency of the chromosome 7 observed in our patient was never described before and we did not find any known gene localized within the deficient segment that could be related to her findings of hypoplastic iliac bones, hypoplastic labia minora and postaxial polydactyly. This case highlights the fact that rare viable recombinants can be developed from PAIs, an issue that must be discussed in the genetic counseling.

Angiosarcoma in a 3-year-old child with congenital lymphedema

Angiosarcoma occurring in chronic lymphedema has been described in more than 200 cases, especially in the upper extremity following radical mastectomy (Stewart-Treves syndrome). However, angiosarcoma developing in congenital lymphedema is quite rare and the literature presents only 14 cases. Our patient is a girl with congenital lymphedema of the left lower limb that developed an angiosarcoma at 3 years of age, noted initially as a painful nodular lesion on the left thigh. This seems to be the earliest presentation of angiosarcoma associated with lymphedema. It claims attention to a careful evaluation of any lesions in a child with lymphedema to provide a better prognosis, which is allowed by precocious diagnosis and rapid interventions.

Combined chemotherapy and teratogenicity.

BACKGROUND: The concomitant occurrence of breast cancer and pregnancy is relatively uncommon. We report the case of a patient with syndactyly, cleft hands, and absence of distal finger phalanges associated with maternal exposure to chemotherapeutic agents during the first trimester of pregnancy. These associations have not been previously described. CASE: The patient was born by normal delivery after 38 weeks of pregnancy. His mother became pregnant while receiving chemotherapy (cyclophosphamide, 5-fluorouracil, and adriamycin) for breast cancer, and the fetus was exposed to these drugs from conception to the 16th week of pregnancy. At birth, anomalies were observed, including a high-arched palate, microcephaly, a flat nasal bridge, bilateral syndactyly in the first and second fingers with a hand cleft between the second and third fingers and hypoplasia of the fifth fingers, and dystrophic nail of the fourth finger of the left hand. The patient's growth and development were deficient. CONCLUSIONS: The malformations associated with in utero exposure to these chemotherapeutic agents are highly variable, but growth deficiency and anomalies of the craniofacial region and limbs are the most common. The pattern of malformations in children who were congenitally exposed to chemotherapeutic agents appears to be directly related to the age at and duration of exposure, rather than to the specific drug itself. Effective contraception is essential for the safe use of a potential teratogen in nonpregnant women of reproductive age.