Prognostic factors for epileptic seizures in severe motor and intellectual disabilities syndrome (SMIDS)--a clinical and electroencephalographic study.

PURPOSE: The purpose of this study is to examine prognostic factors for seizures in 106 epileptic patients with SMIDS. SUBJECTS AND METHODS: One-hundred-six epileptic patients with SMIDS were the subjects of this study. The study group consisted of 60 male and 46 female patients. The ages ranged from 4 to 61 years. They were all followed up for more than 4 years in our residential facility hospital "Kobato Gakuen". Fourteen possible prognostic factors were investigated statistically, and the validity is studied by factor analysis (principal component method). RESULTS: Statistically significant poor prognostic factors for epileptic seizures in SMIDS were (1) status epilepticus; (2) multifocal spikes (MFS) or Diffuse spike and waves (DSW) on final EEG; (3) symptomatic generalized epilepsy; (4) MFS or DSW on first EEG; (5) multi-antiepileptic drugs; (6) postnatal etiology; and (7) short duration of institutional hospitalization. As a result of factor analysis, the following five factors are elucidated: (1) Age/Time Passage; (2) Status epilepticus/Etiology; (3) Epileptic syndrome/EEG; (4) intensive medical care; and (5) Severity of Disabilities/Gender. CONCLUSION: Our findings indicate that intractability of epilepsy may be identified early in the course of the disease, even in SMIDS, and EEG and epileptic syndrome are the very important factors for predicting the seizure prognosis.

Epilepsy in severe motor and intellectual disabilities syndrome (SMIDS)--a clinical and electroencephalographic study of epileptic syndromes.

The subjects were 106 SMIDS with epilepsy. They were classified into four epileptic syndromes: (1) SE-MISF (34.0%), (2) SGE (25.5%), (3) SLRE (20.7%), and (4) epileptic discharge-free patients (EDFP) (19.8%). Clinical electroencephalographic studies elucidated the following result: (1) The seizure disappearance rate was the highest in SLRE (54.5%), and it decreased in the order of EDFP (47.6%), SE-MISF (36.1%), and SGE (11.1%). (2) Status epilepticus was most frequently seen in SGE (62.4%), but it was not so often seen in EDFP (14.3%) or SLRE (22.7%). (3) The age at seizures onset was the lowest in SE-MISF (0.84 years), and it increased in the order of SLRE (1.3), SGE (2.3), and EDFP (6.7). (4) The rate of Ohshima's classification 1 was highest in SE-MISF (61.1%) and lowest in SGE (40.7%). In conclusion, epileptic syndrome and EEG findings are good indicators for predicting the seizure prognosis and some of the clinical features, and the majority of epileptic syndromes could be classified by the very first EEG findings. Since epilepsy in SMIDS is so frequent (70.3%) and intractable (seizure disappearance rate more than 3 years, 36.2%), more attention should be paid to electroencephalography and epileptic seizures in SMIDS.

Two cases of partial trisomy 21 (pter-q22.1) without the major features of Down syndrome.

We report two cases of partial trisomy 21 with clinical features distinct from Down syndrome (DS). These patients presented with moderate mental retardation and short stature, but the typical facial appearance of DS was not observed. Each patient had a similarly sized extra chromosome 21. We performed FISH analysis to examine whether deletions of reported approximately 5 Mb DS critical region (DSCR) might be associated with unusual clinical features in these cases. The results showed that each of their extra chromosomes 21 contained a distal part of chromosome 3p or 14q at the telomeric region of chromosome 21q. The translocation breakpoint of 21q for each patient was located on the centromeric side of DSCR (DSCR was deleted) and the sizes of partial trisomy 21 in respective patients are approximately 34.5 (21pter-q22.12) and approximately 33.0 Mb (21pter-q22.11). In one patient, the additional region of the short arm of chromosome 3 was 3pter-p26.1 from maternal origin, measuring approximately 9 Mb in size. The second patient had an extra 14q32.1-qter of maternal origin, measuring approximately 14 Mb in size. These are one of the shortest partial distal trisomy among reported cases. Taken together, two patients with partial trisomy 21 lack all of DSCR on 21q22, and their distinct clinical features are likely caused by the genes located at 21pter-q22.1 and the distal part of chromosome 3p or 14q.

[Tracheostomy for home-care patients with severe motor and intellectual disabilities].

We discuss here the indication and complications of tracheostomy performed in 57 home-care pateints with severe motor and intellectual disabilities (SMID) during the past 13 years at our hospital. Thirty-five cases underwent tracheostomy following emergency endotracheal intubation for acute respiratory failure. Recently, the number of cases without preceding endotracheal intubation have increased. Many patients underwent tracheostomy at the age of 1 to 4 years and 10 to 14 years. The quality of life (QOL) of almost all the patients without preceding intubation markedly improved, as well as that of their families, and they were able to return to home. The most decisive reason for tracheostomy was secretions and recurrent aspiration pneumonia in 8 patients, gastroesophageal reflux in 4 and upper airway obstructions in 3. Several complications of tracheostomy were observed: tracheal granulations in 9 patients, tracheal malacia in 8, and tracheoinnominate artery fistula in 5. Among 8 patients with tracheal malacia, bleeding from the tracheoinnominate artery fistula occurred in 3. In 7 patients, self-made long tracheostomy tubes were necessary for the initial management of the tracheal malacia or tracheal granulations. Subsequently, made-to-order long tracheostomy tubes were used in three of these patients. In 12 patients, improved endotracheal T-tube with the tip sealed on the vocal cord side was used to prevent aspiration. Home-care SMID patients with respiratory disturbance require tracheostomy timely performed, followed by careful observation to prevent postoperative complications.

[Clinical symptoms of the Rett syndrome patients with MECP2 gene abnormalities].

Mutations in a gene on the X-chromosome encoding methyl-CpG-binding protein 2 (MECP2) cause Rett syndrome. We examined clinical symptoms of 27 patients with Rett syndrome (aged 2 to 37 years), diagnosed by the criteria of the Rett Syndrome Diagnostic Criteria Work Group. having MECP2 gene mutations. Two novel MECP2 mutations, 119 del AG resulting in amino acid frame-shift 40fs43X and C to G transversion resulting in amino acid change of F157L, were found. All patients had the most important symptoms of this syndrome, including loss of acquired purposeful hand skills followed by stereotyped hand movements. Two patients had mild perinatal abnormalities. Nine showed psychomotor delay or hypotonia before 6 months. Five patients over 4 years old did not have microcephaly. Speech was preserved in five patients. According to the criteria, 18 cases were diagnosed as Rett syndrome variants. Sixteen out of 26 patients over 3 years old were able to walk (61.5%), and 22 had epilepsy (84.6%). Mutations of the 5 patients without microcephaly were R133C, P225R, R255X, R306C and 376fs386X, whereas those of the 5 variants with preserved speech were 34fs123X, R133C, R255X and R270. Common T158M mutation was detected in 4 patients, R255X in 7 and R270X in 4. Patients with the same mutations showed different phenotypes. Patients with R133C and R306C presented a mild phenotype without microcephaly. Of the proposed diagnostic criteria, the following three may not be essential: apparently normal prenatal and perinatal period, apparently normal psychomotor development through the first 6 months, and deceleration of head growth between 5 months and 4 years.

A novel mutation, P126R, in a Japanese patient with HHH syndrome.

Mitochondrial ornithine transporter deficiency, or HHH syndrome, is a metabolic disorder resulting in various neurologic symptoms, including mental retardation, spastic paraparesis with pyramidal signs, cerebellar ataxia, and episodic disturbance of consciousness or coma caused by hyperammonemia. Several mutations have been reported in the ORNT1 gene encoding mitochondrial ornithine transporter of patients with this disorder. In this article, we report a new patient, a male 15 years of age, who had typical clinical features of HHH syndrome. Because the patient did not have any of the three mutations previously described in other Japanese patients with HHH syndrome, and the only material available from the patient was peripheral leukocytes, we established a genomic polymerase chain reaction method using intronic primers to amplify every exon of the ORNT1 gene, and we directly sequenced the polymerase chain reaction products. Using this method, we documented a novel mutation in this patient, P126R, and demonstrated that HHH syndrome is genetically heterogeneous, even in the Japanese population.