Figura. Resonancia magnética cerebral con secuencias en T1 en corte coronal y en T2 en corte axial. a, b) Las imágenes muestran las sustancias blanca y gris sin ninguna anormalidad cerebral; c, d) La resonancia magnética del paciente a los 9 meses de edad mostró la sustancia blanca hemisférica difusamente anormal con edema (flecha en d) y quistes subcorticales en la región temporal anterior (flecha en c); e, f) La resonancia magnética control a los 16 meses no mostró cambios significativos.
Tabla I. Hallazgos clínicos asociados a patrones genéticos [7]. |
|||
MLC1 |
HEPACAM (AR) |
HEPACAM (AD) |
|
Macrocefalia |
Primer año de vida (mantenida) |
Primer año de vida (mantenida) |
Primer año de vida (puede normalizarse) |
Deambulación en la edad adulta |
Puede no lograrse |
Preservada |
Preservada |
Afectación según el GMFS |
Variable |
Variable |
Menor |
Rasgos de TEA |
9% |
0% |
25% |
Inicio epiléptico antes de los 20 años |
62% |
69% |
12% |
Alteración cognitiva |
63% |
69% |
27% |
Aumento del espacio subaracnoideo |
24% |
40% |
60% |
Presencia de quistes |
100% |
100% |
50% |
Afectación cerebelosa en la RM |
89% |
60% |
10% |
AD: autosómico dominante; AR: autosómico recesivo; GMFS: Gross Motor Function Classification System; RM: resonancia magnética; TEA: trastorno del espectro autista. |
Tabla II. Criterios de diagnóstico para la leucoencefalopatía megalencefálica con quistes subcorticales [4]. |
Macrocefalia en el primer año de vida |
Ausencia o lento deterioro neurológico |
Diferentes anomalías en la sustancia blanca cerebral con signos de edema de la sustancia blanca |
Preservación relativa de estructuras centrales de la sustancia blanca, como cuerpo calloso, cápsula interna y tallo cerebral |
Quistes temporales anteriores |
Normalidad de la sustancia gris |
En el seguimiento, atrofia de la sustancia blanca cerebral o mejora progresiva hasta la normalización de la sustancia blanca |
Ausencia de otras patologías |
Megalencephalic leukoencephalopathy with cysts –the clinical importance in the genetic era Introduction. Megalencephalic leukoencephalopathy with cysts is a leukodystrophy of genetic origin that produces an alteration in the water and ion homeostasis in the brain, generating vacuolar forms and chronic oedema in the white matter with progressive neurological deterioration. It should be suspected in infants who present progressive macrocephaly during the first year of life, motor retardation and characteristic findings in magnetic resonance brain scans. Case report. We report the case of a girl who was followed up from the age of 9 months due to progressive macrocephaly and delayed psychomotor development and brain MRI findings consistent with megalencephalic leukoencephalopathy with cysts, and the appearance of epilepsy during its development. The usual genetic studies (new generation sequencing and array) were negative, but as the diagnostic criteria were met, a complementary messenger RNA and DNA study was conducted, which confirmed the presence of two pathogenic variants in MLC1. Conclusions. Megalencephalic leukoencephalopathy with cysts is a rare condition. Progressive macrocephaly in the first year of life, the absence of deterioration or slow deterioration, and the possibility of developing epilepsy, spasticity and ataxia are characteristic signs in its course. It is important for these patients to undergo an imaging test that shows findings that characterise this condition, which, together with the clinical features, makes it possible to differentiate it from other leukodystrophies and to establish a confirmatory diagnosis. Genetic studies can confirm the associated mutation that makes it possible to predict the clinicoradiological phenotype. Key words. Genetic diseases. Leukodystrophy. Magnetic resonance brain scan. Megalencephalic leukoencephalopathy with cysts. Megalencephaly. Progressive macrocephaly. Spasticity. Van der Knaap disease. White matter diseases. |