Síndrome de Miller-Dieker: reporte de dos casos / Miller-Dieker Syndrome: Two Cases Report

Resumen Introducción: El síndrome de Miller-Dieker cuenta con un patrón de herencia autosómico dominante y pertenece al grupo de trastornos de la migración neuronal. Se caracteriza por la presencia de lisencefalia de tipo 1, retraso global del desarrollo, microcefalia, epilepsia y dismorfismos faciales dados por mutaciones en el cromosoma 17p13. El síndrome de Miller-Dieker es una enfermedad extremadamente rara con prevalencia de 1 caso por cada 100,000 recién nacidos vivos. Presentación de casos: Nosotros presentamos dos casos de síndrome de Miller-Dieker en los que datos de la exploración física y del interrogatorio fueron pistas que permitieron una fuerte sospecha diagnóstica y que a su vez el diagnóstico definitivo mediante FISH permitió brindar un adecuado manejo con la finalidad de mejorar el pronóstico a largo plazo. Conclusión: Se debe tener una alta sospecha diagnóstica mediante la exploración física dirigida a identificar alteraciones en pacientes con epilepsia de difícil control, ya que permite guiar el diagnóstico etiológico y con ello brindar un adecuado tratamiento.

Abstract Introduction: Miller-Dieker syndrome has an autosomal dominant pattern of inheritance and belongs to the group of neuronal migration disorders. It is characterized by the presence of type 1 lissencephaly, global development delay, microcephaly, epilepsy and facial dysmorphisms caused by mutations in chromosome 17p13. Miller-Dieker syndrome is an extremely rare disease with a prevalence of 1 case per 100,000 live births. Case presentation: We present two cases of Miller-Dieker syndrome in which data from the physical examination and questioning were clues that allowed a strong diagnostic suspicion and that, in turn, the definitive diagnosis by means of FISH allowed us to provide adequate management in order to improve the long-term prognosis. Conclusion: A high diagnostic suspicion must be achieved through physical examination aimed at identifying alterations in patients with difficult-to-control epilepsy, since it allows guiding the etiological diagnosis and thereby providing adequate treatment.

Split hand/foot malformation with long-bone deficiency and BHLHA9 duplication: A prenatal diagnosis report

Distal limb deformities are congenital malformations with phenotypic variability and high genetic heterogeneity. Split hand/foot malformation, also known as ectrodactyly, is a congenital limb malformation characterized by a defect of the central rays of the hands and/or feet. Split hand/foot malformation with long-bone deficiency (SHFLD) is a rare condition related to a 17p13.3 duplication. Recently, genomic duplications encompassing BHLHA9 have been associated with SHFLD. We report a case of SHFLD presenting with campomelia of the right femur, bilateral agenesis of fibulae, bilateral club feet, and oligosyndactyly of the hands and feet, that was associated with a 17p13.3 duplication, as determined prenatally using array comparative genomic hybridization.

A Case of Miller-Dieker Syndrome with Infantile Spasm and Lennox-Gastaut Syndrome / 대한소아신경학회지

Miller-Dieker syndrome is a contiguous gene deletion syndrome involving chromosome 17p13.3, which is characterized by type 1(classical) lissencephaly and typical craniofacial abnormalities. Children with Miller-Dieker syndrome have profound psychomotor retardation, seizures that often are intractable, chronic feeding problems that lead to recurrent pneumonia, and shortened lifespan. We have experienced a Miller-Dieker syndrome female who has lived to 8years, showing severe mental and motor retardation and intractable epilepsy. She was diagnosed as Miller-Dieker syndrome in the neonatal period, showing typical facial features, type 1 lissencephaly, and chromosome 17p13.3 microdeletion in fluorescence in situ hybridization. Infantile spasm occurred at 4 months of age and progressed to Lennox-Gastaut syndrome at 3 years and 6 months, both of which were not controlled by antiepileptic drugs.

Loss of Heterozygosity Analysis of Chromosome 17p13.1-13.3 and Its Correlation with Clinical Outcome in Medulloblastomas / 대한소아혈액종양학회지

PURPOSE: Cytogenetic studies molecular genetic studies, including loss of heterozygosity (LOH) studies, have shown that deletions on the short arm of chromosome 17 (17p) distal to TP53 locus are the most common genetic events in medulloblastoma, and that these occur in 30 to 50% of medulloblastomas. We examined the occurrences and frequencies of allelic deletions on chromosome 17p13.1-13.3 by LOH analysis to investigate the possible involvement of 17p13.1-13.3 in medulloblastoma development. We also performed survival analysis to determine whether LOH analysis of 17p13.1-13.3 can be used to predict prognosis in medulloblastoma. METHOD: LOH was analyzed by polymerase chain reaction (PCR) on chromosome 17p13.1-13.3 using 3 microsatellite markers, TP53 on 17p13.1, D17S796 on 17p13.1-13.2 and D17S1574 on 17p13.3, in 17 medulloblastoma DNAs extracted from archival tissue specimens (cases 1~15) or fresh frozen tissue specimens (cases 16 and 17). RESULTS: Allelic deletions were detected in 5 of 17 informative cases (29%) on TP53, 8 of 17 informative cases (47%) on D17S796, and 4 of 17 informative cases (24%) on D17S1574. Overall, 9 of 17 cases (53%) showed LOH on chromosome 17p13.1-13.3. The 5-year progression free survival (PFS) and 5-year overall survival (OS) rates were identical (59%). The 5-year PFS for 9 medulloblastoma patients with LOH on 17p13.1-13.3 was 56%, and the 5-year PFS for 8 medulloblastoma patients without LOH on 17p13.1-13.3 was 63%. In our survival analysis, we did not find a significant association between survival and LOH on 17p13.1-13.3. CONCLUSION: Our results support the notion that deletions of chromosome 17p13.1-13.3 may be involved in the pathogenesis of medulloblastoma. From survival analysis, we conclude that LOH on chromosome 17p13.1-13.3 may not be a significant predictor of prognosis in medulloblastoma.

Loss of Heterozygosity on Chromosome 9p21, 17p13 and 3p in Human Astrocytic Tumor

BACKGROUND: The purpose of this study was to determine the genetic abnormalities of chromosomes 9p21, 17p13.1, 3p25 and 3p14.2 in the development and progression of astrocytic tumors. METHODS: We performed loss of heterozygosity (LOH) analysis in 41 astrocytic tumors, including 20 astrocytomas, 11 anaplastic astrocytomas and 10 glioblastomas, and correlated the results of LOH at different histopathologic grades. LOH was determined by multiplex polymerase chain reaction analysis of the DNA, which was extracted by microdissection. RESULTS: LOH of 9p21 was found in 55.6% of astrocytomas, 54.6% of anaplastic astrocytomas and 100.0% of glioblastomas. LOH of 17p13.1 was found in 21.4% of astrocytomas, 28.6% of anaplastic astrocytomas, and 66.7% of glioblastomas. LOH of 3p25 was found in 37.5% of astrocytomas, 16.7% of anaplastic astrocytomas, and 14.3% of glioblastomas. LOH of 3p14.2 was found in 16.7% of astrocytomas, 40.0% of anaplastic astrocytomas, and 42.9% of glioblastomas. LOH on chromosome 9p21 and 17p13.1 was closely related with the histopathologic grades. CONCLUSIONS: These results may suggest that LOH of 9p21, 17p13.1, 3p25 and 3p14.2 involves an early event of astrocytoma development and accumulates during progression. LOH of 3p25 may be involved in the tumorigenesis of astrocytoma. Identification of these LOH may illuminate the stepwise pathogenesis of astrocytic tumors and predict the possibility of malignant transformation.

A Case of Miller-Dieker Syndrome

Miller-Dieker Syndrome consists of severe type I lissencephaly and a characteristic abnormal facial appearance at birth and may progress to severe neurologic defects such as intractable seizure and growth failure. This syndrome is associated with microdeletion of p13.3 in the distal portion of chromosome 17. Lissencephaly is a brain malformation manifested by a smooth cerebral surface, thickened cortical mantle, and microscopic evidence of incomplete neuronal migration. We diagnosed Miller-Dieker syndrome in a case in which there are charcteristic craniofacial appearance and neurologic symptoms and type I lissencephaly on the MRI. : We confirmed this syndrome with the a microdeletion of p13.3 portion in the short arm of chromosome 17 by the FISH method. We have experienced a baby with this syndrome, who showed characterisic craniofacial abnormalities and a microdeletion of p13.3 portion in the short arm of chromosome 17. Then we report this rare case with brief review of literature.