1/163. monosomy 18q syndrome and atypical rett syndrome in a girl with an interstitial deletion (18)(q21.1q22.3). We describe a 6 1/2-year-old girl with an interstitial deletion of chromosome arm 18q (18q21.1q22.3). Her clinical manifestations are a combination of those found in monosomy 18q syndrome and those of rett syndrome. cytogenetic analysis demonstrated a deletion of the long arm of chromosome 18, defined by molecular analysis with polymorphic markers as a de novo interstitial deletion, paternally derived. The findings typical of the 18q- syndrome included mental retardation, midface hypoplasia, and hypoplasia of labia majora, and those typical of rett syndrome were severe mental retardation, autistic behavior, inappropriate hand-washing movements, epilepsy, attacks of sighing and hyperventilation, and progressive scoliosis since the age of 5 years. She did not have microcephaly, and the mental delay was obvious from an early age without a period of normal development, which makes the diagnosis of rett syndrome atypical. Previously, a girl with mosaicism for a monosomy 18q associated with rett syndrome has been described. That girl had a terminal deletion of chromosome 18q, which seems to coincide in part with that in the present girl. It is possible that genes in the distal region of 18q are involved in the etiology of rett syndrome. ( info) |
| We studied the circadian rhythm of serum melatonin levels in two patients with classical rett syndrome having severe sleep disorders; serum melatonin levels were measured before and during melatonin treatment using radioimmunoassay. Patient 1 had a free-running rhythm of sleep-wake cycle from 3 years of age. At the age of 4 years, the peak time of melatonin was delayed 6 h compared to normal control and the peak value was at the lower limit. Patient 2 had a fragmented sleep pattern accompanied by night screaming from 1 year and 6 months of age. At the age of 10 years, the peak time of melatonin secretion was normal but the peak value was at the lower limit. These patients were given 5 mg melatonin orally prior to bedtime. Exogenous melatonin dramatically improved the sleep-wake cycle in patient 1. In patient 2, exogenous melatonin showed a hypnotic effect but early morning awakenings occurred occasionally. When melatonin treatment was stopped, the sleep disorders recurred and re-administration of 3 mg melatonin was effective in both patients. The effect was maintained over 2 years without any adverse effects. These findings suggests that sleep disorders in patients with rett syndrome may relate with an impaired secretion of melatonin. ( info) |
| rett syndrome is a unique and puzzling disorder noted in females and is possibly caused by fundamental failures in critical brain connectivity during early infancy. The most frequent habits in rett syndrome are hand sucking or biting, bruxism and mouth breathing. Children with musculoskeletal disorders and children who suffer from mental retardation commonly grind their teeth. A five year old female case with rett syndrome is presented with significant bruxism in this article. ( info) |
4/163. Male rett syndrome variant: application of diagnostic criteria. Classic rett syndrome (RS) has been described in females only. Although an x chromosome origin is probable, it has not been substantiated. It is possible, therefore, that RS could occur in males. The authors describe a male with RS and review all the reported cases involving male patients. The authors compare their patient to the other patients and examine the applicability of the classic RS diagnostic criteria to this variant. To date, nine male patients with RS have been reported. The authors describe an additional male who met seven of nine necessary criteria and six of eight supportive criteria as defined by the RS Diagnostic Criteria work Group. When the authors applied these criteria to the other nine reported patients, many necessary inclusion criteria were not met despite the absence of exclusion criteria. The supportive criteria were even more variable and limited in many patients. In conclusion, males with RS appear to represent a heterogeneous phenotype, with clinical features that may meet many but not all of the necessary diagnostic criteria of classic RS. Less restrictive criteria are needed to include this variant, which should be considered when evaluating males with idiopathic developmental regression, autistic features, and loss of hand function. ( info) |
5/163. Congenital variant rett syndrome in a girl with terminal deletion of chromosome 3p. A girl fulfilling four/five of six inclusion criteria and eight/nine of 11 supportive criteria for atypical rett syndrome had a cytogenetic deletion of chromosome 3p, del(3)(pter-->3p25.1 approximately 25.2). The deletion was situated on the maternally derived chromosome and by molecular analysis the deletion breakpoint was shown to be between dna markers D3S3589 and D3S1263. ( info) |
6/163. rett syndrome: photographic evidence of rapid regression. rett syndrome is known to occur in females, around the second year, with loss of hand use, onset of stereotypes and acquired microcephaly. Such regression is often very rapid, but this has never been documented. In one of our patients, photographs taken at different times clearly demonstrate the rapid progression of first symptoms. Moreover, in the present case, the occurrence of a febrile illness, which preceded the onset of the neurological picture, support the hypothesis that environmental factors may trigger the onset of rett syndrome in genetically predisposed subjects. ( info) |
| We report a 12-year-old girl with features of the syndrome of microcephaly, mesobrachydactyly, and tracheoesophageal fistula, who also developed distinctive features of rett syndrome including regression of milestones with repetitive actions, autistic-like behavior, stereotypic hand movements, and seizures. This unique combination of clinical manifestations appears to constitute a "new syndrome." We speculate that this association may represent a contiguous gene syndrome. ( info) |
8/163. Novel de novo nonsense mutation of MECP2 in a patient with rett syndrome. Because of the recent identification of several mutations of methyl-cpg-binding protein 2 (MECP2) in patients with rett syndrome (RTT), a patient with suspected RTT from an autism clinic was screened for mutations. She was found to have a novel heterozygous nonsense mutation, 129C>T (Q19X), which leads to the most severely truncated MECP2 protein reported to date. Sequencing of parental dna revealed the mutation was de novo. The patient was not affected with microcephaly or hyperventilation, but had other features of rett syndrome including severe mental retardation and symptoms of autistic disorder. Moderately skewed X-chromosome inactivation (XCI) may have contributed to her relatively mild phenotype. ( info) |
| rett syndrome is a progressive neurodegenerative disease of unknown etiology. Reported here are three children who presented with all clinical features of rett syndrome. The aim of this presentation is to alert physicians to the existence of this progressive brain disease which only affects girls and so far no specific treatment has been suggested. ( info) |
| rett syndrome (RTT) is a progressive neurodevelopmental disorder that affects one in 10,000-15,000 females. RTT is mainly sporadic; familial cases have an estimated frequency of less than 1%. Before the recent identification of de novo dominant mutations in the X-linked MECP2 gene, many other hypotheses had been proposed to explain the particular pattern of inheritance and the phenotypic expression of the disease. The involvement of mitochondrial dna had been investigated because of the structural and functional mitochondrial abnormalities evident in the patients. In 1997 the finding of mutations at 16S rRNA in several affected RTT females and their mothers was reported, suggesting that mitochondrial dna might play a key role in the pathogenesis of RTT. To investigate the relevance of such mutations, we used the same methodologic approach to analyze RTT mitochondrial dna in our series. No 16S rRNA alterations were evident in 27 Spanish patients with classic RTT. ( info) |