[Dandy-Walker malformation associated with extracranial abnormalities in a newborn]. / Malformación de Dandy-Walker asociada a malformaciones extracraneales en un neonato.

Hydrocephalus is a clinical condition that consists of an accumulation of cerebrospinal fluid around the brain; Dandy- Walker syndrome is a rare cause of it. We present the case of a newborn with prenatal diagnose of hydrocephalus due to a Dandy-Walker malformation, as well as ambiguous genitalia. After birth, diagnosis of Dandy-Walker malformation associated with uncommon extracranial manifestations is confirmed. Specifically, the baby presents interscrotal hypospadias and coronary sinus dilatation due to the persistence of the left superior vena cava. With the exposition of this case, we bring Malformación de Dandy-Walker asociada a malformaciones extracraneales en un neonato Dandy-Walker malformation associated with extracranial abnormalities in a newborn out the complexity of the Dandy-Walker syndrome due to the malformations associated with it; the ones that will determine the prognosis and the need of a multidisciplinary treatment.

La hidrocefalia es una condición clínica que consiste en un cúmulo de líquido cefalorraquídeo a nivel encefálico. Una de las causas, poco frecuente, es el síndrome de Dandy-Walker. Se presenta el caso de un recién nacido con diagnóstico prenatal de hidrocefalia secundaria a una malformación de Dandy- Walker y sospecha de genitales ambiguos. Tras el nacimiento, se confirma el diagnóstico prenatal de malformación de Dandy-Walker asociado a manifestaciones extracraneales poco frecuentes como hipospadias interescrotal y dilatación del seno coronario secundario a persistencia de la vena cava superior izquierda. Con este caso clínico queremos exponer la complejidad del síndrome de Dandy-Walker debido a sus múltiples asociaciones, que marcarán el pronóstico del paciente y la necesidad de tratamiento multidisciplinar.

Malformación de Dandy-Walker asociada a malformaciones extracraneales en un neonato / Dandy-Walker malformation associated with extracranial abnormalities in a newborn

La hidrocefalia es una condición clínica que consiste en un cúmulo de líquido cefalorraquídeo a nivel encefálico. Una de las causas, poco frecuente, es el síndrome de Dandy-Walker. Se presenta el caso de un recién nacido con diagnóstico prenatal de hidrocefalia secundaria a una malformación de Dandy-Walker y sospecha de genitales ambiguos. Tras el nacimiento, se confirma el diagnóstico prenatal de malformación de Dandy-Walker asociado a manifestaciones extracraneales poco frecuentes como hipospadias interescrotal y dilatación del seno coronario secundario a persistencia de la vena cava superior izquierda. Con este caso clínico queremos exponer la complejidad del síndrome de Dandy-Walker debido a sus múltiples asociaciones, que marcarán el pronóstico del paciente y la necesidad de tratamiento multidisciplinar.

Hydrocephalus is a clinical condition that consists of an accumulation of cerebrospinal fluid around the brain; Dandy-Walker syndrome is a rare cause of it. We present the case of a newborn with prenatal diagnose of hydrocephalus due to a Dandy-Walker malformation, as well as ambiguous genitalia. After birth, diagnosis of Dandy-Walker malformation associated with uncommon extracranial manifestations is confirmed. Specifically, the baby presents interscrotal hypospadias and coronary sinus dilatation due to the persistence of the left superior vena cava. With the exposition of this case, we bring out the complexity of the Dandy-Walker syndrome due to the malformations associated with it; the ones that will determine the prognosis and the need of a multidisciplinary treatment

Comprehensive genomic diagnosis of non-syndromic and syndromic hereditary hearing loss in Spanish patients.

BACKGROUND: Sensorineural hearing loss (SNHL) is the most common sensory impairment. Comprehensive next-generation sequencing (NGS) has become the standard for the etiological diagnosis of early-onset SNHL. However, accurate selection of target genomic regions (gene panel/exome/genome), analytical performance and variant interpretation remain relevant difficulties for its clinical implementation. METHODS: We developed a novel NGS panel with 199 genes associated with non-syndromic and/or syndromic SNHL. We evaluated the analytical sensitivity and specificity of the panel on 1624 known single nucleotide variants (SNVs) and indels on a mixture of genomic DNA from 10 previously characterized lymphoblastoid cell lines, and analyzed 50 Spanish patients with presumed hereditary SNHL not caused by GJB2/GJB6, OTOF nor MT-RNR1 mutations. RESULTS: The analytical sensitivity of the test to detect SNVs and indels on the DNA mixture from the cell lines was > 99.5%, with a specificity > 99.9%. The diagnostic yield on the SNHL patients was 42% (21/50): 47.6% (10/21) with autosomal recessive inheritance pattern (BSND, CDH23, MYO15A, STRC [n = 2], USH2A [n = 3], RDX, SLC26A4); 38.1% (8/21) autosomal dominant (ACTG1 [n = 3; 2 de novo], CHD7, GATA3 [de novo], MITF, P2RX2, SOX10), and 14.3% (3/21) X-linked (COL4A5 [de novo], POU3F4, PRPS1). 46.9% of causative variants (15/32) were not in the databases. 28.6% of genetically diagnosed cases (6/21) had previously undetected syndromes (Barakat, Usher type 2A [n = 3] and Waardenburg [n = 2]). 19% of genetic diagnoses (4/21) were attributable to large deletions/duplications (STRC deletion [n = 2]; partial CDH23 duplication; RDX exon 2 deletion). CONCLUSIONS: In the era of precision medicine, obtaining an etiologic diagnosis of SNHL is imperative. Here, we contribute to show that, with the right methodology, NGS can be transferred to the clinical practice, boosting the yield of SNHL genetic diagnosis to 50-60% (including GJB2/GJB6 alterations), improving diagnostic/prognostic accuracy, refining genetic and reproductive counseling and revealing clinically relevant undiagnosed syndromes.