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.

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.

Gómez-López-Hernández syndrome in a child born to consanguineous parents: new evidence for an autosomal-recessive pattern of inheritance?

BACKGROUND: Gómez-López-Hernández syndrome is a rare genetic disease characterized by scalp alopecia with trigeminal anesthesia, brachycephaly or turribrachycephaly, midface retrusion, and rhombencephalosynapsis. We report the second case with this condition who presented with consanguineous parents. PATIENT: This boy was evaluated shortly after birth because of suspected craniosynostosis. He was the only son of healthy, consanguineous parents (his maternal grandmother and his paternal great-grandfather were siblings). His examination was notable for turribrachycephaly, prominent forehead, bilateral parietotemporal alopecia, midfacial retrusion, anteverted nostrils, micrognathia, low-set and posteriorly rotated ears, and short neck with redundant skin. Radiographs and tridimensional computed tomography scan of skull revealed lambdoid craniosynostosis. Brain magnetic resonance imaging revealed complete rhombencephalosynapsis, aqueductal stenosis, fused colliculi, abnormal superior cerebellar penducle, mild ventriculomegaly, and dysgenesis of the corpus callosum. CONCLUSIONS: Since its first description, 34 patients with this condition have been reported. The etiology of Gómez-López-Hernández syndrome is unknown. However, it is noteworthy that the patient in this report presented with a family history of consanguinity because this finding reinforces the possibility of an autosomal-recessive inheritance for this condition.

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.