[Clinical phenotypes of classic Rett syndrome]. / Fenotipos clínicos del síndrome de Rett clásico.

INTRODUCTION: Rett syndrome (RS) is a progressive neurological disorder that is diagnosed by essential, supportive and exclusion clinical criteria, and development takes place in four stages. It has been shown to be caused by de novo mutations of a gene located in the long arm of the dominant X chromosome that codes for the methyl CpG binding protein (MECP2). It has been observed that girls with classic RS (CRS) present distinguishing nuances with respect to the age of onset of the different criteria and as regards the progression of the disorder. Taking the ability or failure to walk as a reference, we have established three phenotypes. METHOD: Phenotype I. Ambulant CRS, which corresponds to a permanent stage III, or a stage III that lasts a long time before going into stage IV. The loss of the ability to use the hands in a purposeful way takes place at the age of 25.6 months, social withdrawal at 25.4 months, language impairment at 20 months, stereotypic hand movements at 22.8 months and signs of spasticity appear around the age of 8-10 years. Phenotype II. Ambulant CRS. Transitory, which corresponds to an early stage IV-A. The first signs of abnormality appear around the age of 9-10 months. This is followed by the loss of the purposeful use of the hands towards the age of 23.4 months, social withdrawal around 21.4 months, language impairment at 20 months, stereotypic hand movements at 25.2 months and scoliosis, neuromotor disorders and trophic and vasomotor disorders at the age of 4-5 years. Phenotype III. Non ambulant CRS, which corresponds to stage IV-B. It begins with hypotonia towards the age of 5-6 months, loss of voluntary grasping at 17.8 months, social withdrawal at 18 months, language impairment at the age of 12 months, stereotypic hand movements at 13 months and early onset of motor, trophic and vasomotor disorders. Genetic studies were conducted in 12 girls and MECP2 gene mutations were found in 10 of them, belonging to the three different phenotypes. CONCLUSIONS: We have established three phenotypes in RS according to the ability to walk. If walking is not achieved or the ability is lost early on, speech loss, social withdrawal and the onset of stereotypic movements, motor, trophic and vasomotor disorders all progress more quickly. Mutations in the MECP2 gene have been found in the three phenotypes. In 16.6% the genotype was normal. Greater accuracy is required in the definition of cases of CRS in order to establish phenotype genotype correlations.

[Clinical course of epileptic seizures in Rett's syndrome]. / Evolución de las crisis epilépticas en el síndrome de Rett.

INTRODUCTION: Seventeen girls diagnosed as Rett syndrome (RS) patients suffer or have suffered epileptic fits; we have analyzed the evolution of these seizures. The RS diagnosis is based on criteria established by the Rett Syndrome Diagnostic Criteria Working Group in 1988. PATIENTS AND METHODS: All girls have had clinical, biochemical, electroneurophysiological neuroimaging and cytogenetic studies done on them. Periodic EEG were carried out while the girls were awake; all had night-time EEGs done. The females are aged between 7 y 5 m, and 22 y 7 m (medium 14 years, 8 months). The age at first seizure was between 18 m and 7 y 8 m (median 4 years 5 months). RESULTS: The clinic semiology is in decreasing order: tonic, generalized clonic, partial, absence and myoclonic seizures; eight patients have had more than one type of seizures. The frequency is variable: one or more continuous seizures in 6 cases, sporadic seizures in 3 cases, series of seizures in 4 cases, and subnitrant seizures in 4 cases. The evolution is variable: 6 cases have presented only the first fit, and 11 cases recurrent seizures which in 5 have ceased between 8 and 9 years, and 1 case at 13 years. CONCLUSIONS: The study shows that the epileptic seizures in RS present three evolution profiles: 1. One or more non recurrent seizures (35.3%); 2. Recurrent seizures until 8-9 years (35.3%); 3. Recurrent seizures in subnitrant form which continued after puberty (29.4%).

[Contribution to studies of seizures in Rett's syndrome. Analysis of critical forms of four cases]. / Contribución al estudio de las crisis epilépticas en el síndrome de Rett. Análisis de los registros críticos de cuatro casos.

Twenty girls were diagnosed as having Rett's Syndrome (RS) based on criteria decided upon in 1988. Fifteen suffered epileptic fits, four of which were possible to record by EEG. In this work we report on the clinical EEG semiology of these girls. All underwent clinical, biochemical, electroneurophysical, neuroimaging and cytogenetic studies. Periodic EEG were carried out while the girls were awake and the recorded fits were so obtained. All had night-time EEG. Four girls had their first fits between 5 years 4 months and 6 years 5 months (average 6 years). The ages at which their attacks were recorded varied from seven to eleven years. Two girls presented tonic-axial attacks expressed graphically by desynchronisation in the EEG in one case and rhythmically in the other, one having had atypical simple absences expressed on EEG as point-wave complexes at a rate of two per second, the other presenting two types of attack: initially tonic-axial fits expressed as a low amplitude rhythm and a year later generalised clonal fits expressed as slow waves with sharp waves in between. Outstanding is the fact that despite the diversity of epileptic fits described in RS all such attacks recorded were of a generalised type.

Familial spastic paraplegia with neuropathy and poikiloderma. A new syndrome?

We report a case study spanning three generations of familial spastic paraplegia, distal amyotrophy and poikiloderma. This study is the first description of an association between these three disorders. The gait disorder, the sensory and motor involvement and the skin disorder coincide in all the affected members, suggesting autosomal dominant inheritance with complete penetrance.