ABSTRACT
Introducción: La hipoplasia pontocerebelosa (HPC) es la reducción del tamaño del cerebelo y la protuberancia secundaria a una alteración en su desarrollo, pudiendo ser provocado por enfermedades neurodegenerativas de causa genética, de las que se conocen 10 subtipos (PCH 1-10), malformaciones corticales, enfermedades metabólicas y enfermedades genéticas. Objetivo: Presentar el caso de una niña con microcefalia, HPC y Síndrome de West, en que el estudio genético permitió llegar al diagnóstico de una deleción en el cromosoma X. Caso clínico: Lactante de 7 meses al diagnóstico, sin antecedentes familiares ni obstétricos de interés, perímetro cefálico (PC) al nacimiento en -1.5 desviaciones estándar (DE). Evolucionó con escasa progresión ponderal y estancamiento del crecimiento del PC, retraso del desarrollo psicomotor, caracterizado por ausencia de fijación de la mirada e hipotonía con reflejos osteotendinosos conservados, y epilepsia refractaria. En los potenciales evocados auditivos se demostró compromiso de las vías pontomesencefálicas y en las neuroimágenes HPC. El estudio genético Array de Hibridación Genómica Comparada (aCGH) demostró deleción parcial heterocigota en el cromosoma X, afectando al gen CASK. Conclusiones: Ante el amplio diagnóstico diferencial que plantea las HPC, las nuevas técnicas citogenéticas han permitido mejorar la clasificación y en algunos casos establecer su etiología, pudiendo ofrecer en estos casos un adecuado asesoramiento genético a las familias.
Introduction: Pontocerebellar hypoplasia (PCH) is a reduction of the size of the cerebellum and pons secondary to an alteration in its development, and can be caused by neurodegenerative diseases of genetic origin, of which there are known 10 subtypes (PCH 1-10), cortical malformations, metabolic and genetic diseases. Objective: To present the case of a child with microcephaly, PCH and West syndrome, in which the genetic study allowed to make the diagnosis of a deletion on chromosome X. Case report: This is a female infant of 7-month at diagnosis, without family or obstetric history of interest, head circumference at birth -1.5 standard deviations (SD). She had little weight and growth in head circumference progression. In addition, physical examination revealed no fixating gaze, hypotonia with preserved deep tendon reflexes. Progressively developed refractary seizures. Brainsteam Auditory Evoked Potential demonstrated involvement of pontomesencefphalic ways and neuroimaging Pontocerebellar hypoplasia. The genetic study (aCGH) showed heterozygous deletion on the X chromosome, affecting the CASK gene. Conclusions: Given the wide differential diagnosis proposed at the PCH, new cytogenetic techniques have improved the classification of HPC and in some cases establish their etiology, so in these cases can provide appropriate genetic counseling to families.
Subject(s)
Humans , Female , Infant , Child, Preschool , Cerebellar Diseases/diagnosis , Cerebellar Diseases/genetics , Gene Deletion , Guanylate Kinases/genetics , Spasms, Infantile/diagnosis , Spasms, Infantile/etiology , Genetic Markers , Cerebellar Diseases/complications , Microcephaly/diagnosis , Microcephaly/etiologyABSTRACT
MICrocephaly, disproportionate pontine and cerebellar hypoplasia (MICPCH) syndrome, a rare X-linked disorder, generally seen in girls, is characterized by neurodevelopmental delay, microcephaly, and disproportionate pontine and cerebellar hypoplasia. It is caused by inactivating calcium/calmodulin-dependent serine protein kinase (CASK) gene mutations. We report a 2-year-old girl with severe neurodevelopmental delay, microcephaly, minimal pontine hypoplasia, cerebellar hypoplasia, and normal looking corpus callosum, with whom the conventional cytogenetic studies turned out to be normal, and an array-comparative genomic hybridization (a-CGH) analysis showed CASK gene duplication at Xp11.4. Our case highlights the importance of using clinico-radiologic phenotype to guide genetic investigation and it also confirms the role of a-CGH analysis in establishing the genetic diagnosis of MICPCH syndrome, when conventional cytogenetic studies are inconclusive.