Autism spectrum disorders are a heterogeneous group of disorders that share the presence of two core symptoms: problems in social interaction / communication and the tendency to present restricted ...interests and repetitive behavior. Over the last years, several epidemiologic studies have been published by different authors in diverse countries, having all of them shown two common characteristics: a global increase in the prevalence rates of autism spectrum disorders, and the existence of a great geographical variability no only between geographical areas, but also within the same geographical areas. At the present manuscript, we analyze some of the most recent prevalence data published in USA and some European countries (including Spain). All of them show different prevalence rates, ranging from 1/59 children with autism spectrum disorders in the USA to 1/806 in Portugal. In a second part, we briefly describe some of the current scientific hypotheses that try to explain this variability.
We report on a girl with cutaneous angioma and hydrocephalus who presented the characteristics of the condition described by Shapiro and Shulman. At birth, she manifested extensive pink discoloration ...on her face, scalp, and back. During infancy, she developed hydrocephalus, which later stabilized. Magnetic resonance angiography revealed anomalous intracranial venous drainage, which led to development of her hydrocephalus. Various authors described such a process in the 1970s and 1980s, interpreting it as a variant of Sturge-Weber syndrome, and listing it with other neurocutaneous syndromes associated with vascular nevi, but few references to this condition appear in the recent literature. We think it exists as a syndrome, and that it is not a variant of Sturge-Weber syndrome. The cutaneous anomaly has characteristics closer to those of vascular birthmarks that fade than those of the port wine stain itself, and seems a direct consequence of abnormal venous drainage rather than a primarily capillary malformation.
Background: Wolf-Hirschhorn syndrome (WHS) is a rare disease caused by deletion in the distal moiety of the short arm of chromosome 4. The objectives of this study were to report the most ...representative oral findings of WHS, relate them with other clinical characteristics of the disease, and establish possible phenotype-genotype correlation. Methods: The study was conducted at 6 reference centers distributed throughout Spain during 2018–2019. The study group consisted of 31 patients with WHS who underwent a standardized oral examination. Due to behavioral reasons, imaging studies were performed on only 11 of the children 6 years of age or older. All participants had previously undergone a specific medical examination for WHS, during which anatomical, functional, epilepsy-related, and genetic variables were recorded. Results: The most prevalent oral manifestations were delayed tooth eruption (74.1%), bruxism (64.5%), dental agenesis (63.6%), micrognathia (60.0%), oligodontia (45.5%), and downturned corners of the mouth (32.3%). We detected strong correlation between psychomotor delay and oligodontia (p = 0.008; Cramér’s V coefficient, 0.75). The size of the deletion was correlated in a statistically significant manner with the presence of oligodontia (p = 0.009; point-biserial correlation coefficient, 0.75). Conclusion: Certain oral manifestations prevalent in WHS can form part of the syndrome’s phenotypic variability. A number of the characteristics of WHS, such as psychomotor delay and epilepsy, are correlated with oral findings such as oligodontia and bruxism. Although most genotype-phenotype correlations are currently unknown, most of them seem to be associated with larger deletions, suggesting that some oral-facial candidate genes might be outside the critical WHS region, indicating that WHS is a contiguous gene syndrome.
BACKGROUND // Wolf-Hirschhorn syndrome is a rare disease of genetic origin caused by the deletion of the distal end of chromosome
4, including at least the region p16.3. The objectives of this work ...were to determine the prevalence of the disease in the Spanish
population, as well as to establish the geographical distribution of the syndrome throughout the Spanish geography, elucidating the
age range in which there are more patients.
METHODS // Patients diagnosed with the disease for nine years (2013-2021) throughout the Spanish territory were recruited for the
research, thanks to agreements with the Spanish Association of Wolf-Hirschhorn Syndrome (AESWH). The clinical information of the
patients was obtained from referring physicians using two standardized questionnaires completed with data from medical reports and
the parent interview. The molecular characterization of the disease was made using SNP (single nucleotide polymorphism) microarrays
(cytoSNP850K, Illumina, USA). The data were statistically processed using Microsoft Excel (Microsoft Corporation) and SPSS (IBM) software,
using comparisons between two groups s with Student’s t-test (for continuous variables) or with Chi-square tests (for categorical ones).
For more than two groups, ANOVA analyses were performed (followed by Bonferroni or T3-Dunnett post hoc tests) for continuous variables
and z-tests between column proportions for categorical variables.
RESULTS // In Spain (until 2021) eighty people are diagnosed with this syndrome, estimating its prevalence at 1.69x10-4 per 10,000
inhabitants and / or 1/172,904 for each live newborn. This paper remarks the existence of important differences in prevalence between
the different regions in Spain. The region with the most diagnosed patients was Madrid, although the highest prevalence was observed
in Asturias. Significant differences have been established in terms of sex and disease (ratio of women to men of 2:1), and the mean
age at diagnosis has been established at 7.20 years.
CONCLUSIONS // The prevalence of this syndrome in Spain has been estimated well below the prevalence that is handled in scientific
texts (1/50,000 newborns). In addition, we have determined that this prevalence shows large geographical differences, which
allows us to affirm that this syndrome could be under-diagnosed in our country. Most of the patients included in this cohort are of
paediatric age. It has not been possible to corroborate that mortality in this syndrome, in our population, occurs preferably during
the first two years of life, as has been claimed.
FUNDAMENTOS // El Síndrome de Wolf-Hirschhorn es una enfermedad poco frecuente de origen genético causada por la deleción
del extremo distal del cromosoma 4, que incluye preferentemente la región p16.3. Los objetivos de este trabajo fueron determinar la
prevalencia de la enfermedad en la población española, así como establecer la distribución geográfica del síndrome a lo largo de la
geografía nacional, dilucidando el rango de edad en el que existían más pacientes afectados.
MÉTODOS // Para la investigación se reclutaron 80 pacientes diagnosticados con el síndrome en el periodo 2013-2021, en todo el
territorio español, gracias a los acuerdos con la Asociación Española de Síndrome Wolf-Hirschhorn (AESWH). La información clínica
de los pacientes se obtuvo mediante dos cuestionarios estandarizados que fueron cumplimentados por médicos de referencia y
los padres, siendo completados y corroborados con los distintos informes médicos de cada paciente y, al menos, una entrevista
una entrevista a los padres. La caracterización molecular de la enfermedad se realizó mediante el uso de microarrays de SNP
(del inglés, single nucleotide polymorphism) (CytoSNP 850K, Illumina). Los datos se trataron estadísiticamente utilizando los softwares
Microsoft Excel (Microsoft Corporation) y SPSS (IBM), mediante las comparaciones entre dos grupos s con la prueba t de Student
(para variables continuas) o con pruebas de Chi cuadrado (para las categóricas). Para más de dos grupos se realizó análisis ANOVA
(seguido de las pruebas post hoc de Bonferroni o T3-Dunnett) para variables continuas y pruebas z entre proporciones de columna
para variables categóricas.
RESULTADOS // En España (hasta 2021) están diagnosticadas ochenta personas con este síndrome, estimándose su prevalencia en
1,69x10-4 por cada 10.000 habitantes y/o 1/172.904 por cada recién nacido vivo. En este trabajo se constató la existencia de importantes
diferencias de prevalencia entre las comunidades autónomas de nuestro país. La comunidad con más pacientes diagnosticados fue
Madrid, aunque la mayor prevalencia se observó en Asturias. Se establecieron diferencias estadísticamente significativas en cuanto al
sexo y la enfermedad (proporción de mujeres sobre varones de 2:1), así como se estableció la edad media al diagnóstico en 7,20 años.
CONCLUSIONES // La prevalencia de este síndrome en España se estima muy por debajo de la prevalencia que se maneja en los
textos científicos (1 por cada 50.000 recién nacidos). Adicionalmente, hemos determinado que esta prevalencia muestra grandes diferencias
geográficas, lo que nos permite afirmar que este síndrome podría encontrarse infra-diagnosticado en nuestro país. La mayor
parte de los pacientes incluidos en esta cohorte se encuentran en edad pediátrica. No se ha podido corroborar que la mortalidad
en este síndrome, en nuestra población, ocurra preferentemente durante los dos primeros años de vida, como se venía afirmando.
El síndrome de Wolf-Hirschhorn es una entidad polimalformativa debida a la microdeleción en la región distal del brazo corto del cromosoma 4 (4p16.3), el cual produce una serie de manifestaciones ...clínicas, que pueden variar dependiendo del tipo y tamaño del defecto genético en este síndrome de genes contiguos. Se presentan cinco pacientes, tres de ellos de sexo femenino, todos con los hallazgos clínicos primordiales, con rasgo facial característico de "apariencia en casco de guerrero griego", retraso en el crecimiento y del desarrollo psicomotor. Además de la deleción parcial en la región distal del brazo corto del cromosoma 4, en dos pacientes, se encontraron alteraciones genéticas adicionales, mediante el uso de microarrays de polimorfismos de nucleótido único. Se resaltan las características clínicas del síndrome de Wolf-Hirschhorn con la finalidad de orientar el diagnóstico, brindar una atención médica interdisciplinaria y, a través de su confirmación, brindar un adecuado asesoramiento genético familiar.
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