Miller-Dieker syndrome (MDS) is a genetic disorder characterized by classic lissencephaly, distinctive facial features, intellectual disability, seizures, and early death. The anesthetic management of patients with MDS should focus on airway manipulation with the risk of potentially difficult intubation, seizure control due to lissencephaly, and any other clinical complications. Herein, we report a case of anesthetic management in a child with MDS and describe relevant clinical features in a perioperative anesthetic setting. This case highlights the importance of difficult airway manipulation using a videolaryngoscope, seizure management with regard to anesthetics use, and the low validity of BIS monitoring in patients with MDS.

17p13.3 microdeletions or microduplications (collectively known as copy number variants or CNVs) have been described in individuals with neurodevelopmental disorders. However, 17p13.3 CNVs were rarely reported in fetuses. This study aims to investigate the clinical significance of 17p13.3 CNVs with varied sizes and gene content in prenatal and postnatal samples.
Eight cases with 17p13.3 CNVs out of 8806 samples that had been subjected to single nucleotide polymorphism array analysis were retrospectively analyzed, along with karyotyping, clinical features, and follow-up.
Eight cases with 17p13.3 CNVs consisted of five fetuses, one aborted embryo and two probands manifested severe congenital defects. The indications of prenatal testing varied considerably for the five fetuses, including ultrasound abnormalities (n = 3), segmental deletions indicated by non-invasive prenatal testing (n = 1), and intellectual disability in the mother of one fetus (n = 1). Of them, two and six harbored copy number gains and losses involving 17p13.3, respectively. The size of the detected 17p13.3 CNVs ranged from 576 kb to 5.7 Mb. Case 1 was diagnosed with 17p13.3 duplication syndrome, and cases 4, 6, and 7 with Miller-Dieker syndrome (MDS). Microdeletions of the 17p13.3 region in two cases (cases 5 and 8) involving YWHAE and CRK, sparing PAFAH1B1, were classified as pathogenic. Case 2 harbored a 576 kb microduplication, encompassing YWHAE and CRK but not PAFAH1B1, which was of maternal origin and considered a variant of uncertain significance. Case 3 carried one 74.2 Mb mosaic duplication of approximately 3.5 on chromosome 17p13.2q25.3, and two deletions at 17p13.3p13.2 and 17q25.3. The karyotype of case 3 was 46,XY,r(17)(p13q25). For five fetuses, only case 2 continued gestation and showed normal development at the age of 15 months; the others were subjected to termination of pregnancy.
The clinical findings of 17p13.3 microdeletions or microduplications varied among subjects, and 17p13.3 CNVs often differ in size and gene content. Microdeletions or microduplications containing the typical MDS region, as well as the microdeletions involving YWHAE and CRK, could be classified as pathogenic. The clinical significance of small duplications including YWHAE and CRK but not PAFAH1B1 remains uncertain, for which parental testing and clinical heterogeneity should be considered in genetic counseling.

Miller-Dieker syndrome (MDS) is a rare genetic disorder characterized by congenital lissencephaly (absent or diminished cerebral gyri), facial dysmorphisms, neurodevelopmental retardation, intrauterine fetal demise, and death in early infancy or childhood. We present a case of a 4-year-old girl with MDS (17p13.3p13.2 deletion) who was admitted to the hospital due to fever and increased secretions from her nose, mouth, and tracheostomy tube (as she had been on a ventilator and G-tube dependent since birth). During the course of hospitalization, she developed multiorgan failure, third spacing, and significant lactic acidosis. The patient had a cardiorespiratory arrest and expired after 4 months and 8 days of hospitalization. We provide a synopsis of the main autopsy findings, with a focus on the neuropathologic anomalies.

The 17p13.3 chromosome region is often deleted or duplicated in humans, resulting in severe neurodevelopmental disorders such as Miller-Dieker syndrome (MDS) and 17p13.3 duplication syndrome. Lissencephaly can also be caused by gene mutations or deletions of a small piece of the 17p13.3 region, including a single gene or a few genes. PAFAH1B1 gene, coding for LIS1 protein, is a responsible gene for lissencephaly and MDS and regulates neuronal migration by controlling microtubules (MTs) and cargo transport along MTs via dynein. CRK is a downstream regulator of the reelin signaling pathways and regulates neuronal migration. YWHAE, coding for 14-3-3ε, is also responsible for MDS and regulates neuronal migration by binding to LIS1-interacting protein, NDEL1. Although these three proteins are known to be responsible for neuronal migration defects in MDS, there are 23 other genes in the MDS critical region on chromosome 17p13.3, and little is known about their functions in neurodevelopment, especially in neuronal migration. This review will summarize the recent progress on the functions of LIS1, CRK, and 14-3-3ε and describe the recent findings of other molecules in the MDS critical regions in neuronal migration.

OBJECTIVE: To evaluate the electroclinical course and the correlation Electroencephalographic (EEG) pattern and epileptic seizures in an infant with Miller Dieker Syndrome (MDS) during the first year of life.
METHODS: MDS was diagnosed in the infant soon after birth and followed up from six months of life to one year, at the Department of Pediatrics, General Pediatric Operative Unit, Policlinico Vittorio Emanuele, University Hospital, XCatania, Italy, with clinical and serial EEG recording.
RESULTS: Aside from severe delay in the developmental milestone, the onset of the seizures was first noticed by the parents at the age of 4 months as brief slow tonic movements; at 6 months as tonic movements of the upper limbs with a slow rotations of the trunk, i.e. \"subtle spams\"; and at 7 months as typical \"infantile spams\" and tonic seizures. The EEG recording registered pattern of modified hypsarrhythmia (MH) correlated with \"subtle spams\" at the age of 6 months and at the age of 7 months the same EEG recording of MH associated to clinical expression of classical Infantile Spams (IS).
CONCLUSIONS: In this infant, the EEG pattern and epileptic seizures were widely variable ranging clinically from brief anomalous movements to \"subtle spams\" and to typical infantile spams. At the same time, the EEG recording manifested first with MH and one month later with classical hypsarrhythmia. The EEG recording MH correlated first with clinical expression of subtle spams and the EEG remaining unchanged with the classical clinical expression of infantile spams.

Miller-Dieker syndrome (MDS) is a rare disorder characterized by type I lissencephaly and a distinctive facial appearance that may include prominent forehead, bitemporal hollowing, and micrognathia. MDS is associated with epilepsy. We here report an 18-month-old girl with MDS who required general anesthesia. The child had an extremely low Bispectral Index (BIS) value prior to undergoing general anesthesia. Her perioperative course was uneventful. This case highlights some of the important anesthetic concerns in patients with MDS, which include potentially difficult airways and extremely low BIS values.

Miller-Dieker syndrome (MDS) is a rare genetic syndrome associated with lissencephaly, developmental delay, and high mortality. We describe a patient who was diagnosed postnatally with both MDS and congenital lobar emphysema. We believe that this is the first reported case of the two conditions presenting in the same patient.

The tumor suppressor gene HIC1 (Hypermethylated In Cancer 1) is located in 17p13.3 a region frequently hypermethylated or deleted in tumors and in a contiguous-gene syndrome, the Miller-Dieker syndrome which includes classical lissencephaly (smooth brain) and severe developmental defects. HIC1 encodes a transcriptional repressor involved in the regulation of growth control, DNA damage response and cell migration properties. We previously demonstrated that the membrane-associated G-protein-coupled receptors CXCR7, ADRB2 and the tyrosine kinase receptor EphA2 are direct target genes of HIC1. Here we show that ectopic expression of HIC1 in U2OS and MDA-MB-231 cell lines decreases expression of the ApoER2 and VLDLR genes, encoding two canonical tyrosine kinase receptors for Reelin. Conversely, knock-down of endogenous HIC1 in BJ-Tert normal human fibroblasts through RNA interference results in the up-regulation of these two Reelin receptors. Finally, through chromatin immunoprecipitation (ChIP) in BJ-Tert fibroblasts, we demonstrate that HIC1 is a direct transcriptional repressor of ApoER2 and VLDLR. These data provide evidence that HIC1 is a new regulator of the Reelin pathway which is essential for the proper migration of neuronal precursors during the normal development of the cerebral cortex, of Purkinje cells in the cerebellum and of mammary epithelial cells. Deregulation of this pathway through HIC1 inactivation or deletion may contribute to its role in tumor promotion. Moreover, HIC1, through the direct transcriptional repression of ATOH1 and the Reelin receptors ApoER2 and VLDLR, could play an essential role in normal cerebellar development.