[Pontocerebellar hypoplasia secondary to CASK gene deletion: Case report]. / Hipoplasia pontocerebelosa secundaria a deleción en el gen CASK: Caso clínico.

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.

Hipoplasia pontocerebelosa secundaria a deleción en el gen CASK: Caso clínico / Pontocerebellar hypoplasia secondary to CASK gene deletion: Case report

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.

The role of CYP2C9 polymorphisms in phenytoin-related cerebellar atrophy.

PURPOSE: Phenytoin is known to be able to induce cerebellar atrophy in patients with epilepsy. It is also known that a CYP2C9 mutation (*2 or *3) reduces phenytoin metabolism by 25-50% and can increase the risk of phenytoin-related side effects. We examined the influence of CYP2C9 polymorphisms on total cerebellar volume and cerebellar gray and white matter volumes in patients with epilepsy taking phenytoin. METHODS: For the genotyping, 100 adult patients with documented epilepsy who had been taking phenytoin for >1 year were selected. From this group, we randomly selected 19 mutant individuals (MT group; CYP2C9*2 and *3) for a whole-brain volume measurement using MRI and 19 wild-type individuals (group WT; CYP2C9*1) with similar clinical and demographic characteristics to those in the MT group for comparison. Total intracranial volume measurements were used to normalize the acquired volumes, which were separated into gray matter volume, white matter volume, and total volume. RESULTS: The MT group exhibited a significant reduction in cerebellar white matter volume (p=0.002) but not in total cerebellar volume. CONCLUSION: Our study is the first to report evidence linking CYP2C9 polymorphism and a reduction in cerebellar volume in epileptic users of phenytoin.

[Joubert syndrome: report of four adult siblings affected]. / Sindrome de Joubert: a propósito de cuatro hermanos adultos afectados.

INTRODUCTION: Joubert syndrome is a rare, autosomal recessive genetic transmission illness, with ten associated genes discovered at the time. They code for primary ciliary proteins; that is why Joubert syndrome is considered a 'ciliopathie'. The primary cilia are involved in cell proliferation and neuronal migration in cerebellum and axonal brain, being essential for their proper development. The first description was made in 1969 by Marie Joubert and colleagues. They reported four cases with partial or total agenesis of the cerebellar vermis, apnea-hyperpnea neonatal episodic, abnormal eye movements, ataxia and mental retardation. One of them also showed occipital meningoencephalocele. CASE REPORTS: Four adult individuals affected by the disease are described. All of them biological siblings, within 24-35 years old, and presenting the 'sign of the molar' midbrain in their clinical and neuroimaging. It is an entity characteristic, with the image formed by agenesis or hypoplasia of the cerebellar vermis, superior cerebellar peduncle narrow, flatten, thickened and elongated with a lack of decussation and deep interpeduncular fossa at the level of the isthmus and upper bridges. CONCLUSIONS: This study shows the need for early disease diagnosis to ensure proper monitoring, therapeutic approach and family genetic counseling, as well as the role of the cerebellum in cognitive functions and intelligence development.

Spinocerebellar degeneration and slow saccades in three generations of a kinship: clinical and electrophysiologic findings.

Four members of a family with spinocerebellar degeneration and slow saccadic eye movements are described. Detailed electrophysiological studies revealed abnormalities of neurological pathways not apparent clinically. The patients had slow saccades as measured electrophysiologically, as well as absence of rapid eye movements (REM) despite REM stages of sleep. These studies suggest that although saccadic eye movement and REM are mediated through the pontine paramedian reticular formation, other characteristics of REM sleep are not necessarily mediated through the same neurons.