1. Fehr S, Downs J, Bebbington A, Leonard H. {{Atypical presentations and specific genotypes are associated with a delay in diagnosis in females with Rett syndrome}}. {Am J Med Genet A} (Sep 2)

There is often delay between onset of Rett syndrome symptoms and its diagnosis, possibly related to symptom presentation or socio-demographic factors. We hypothesized that girls with an atypical presentation or whose family had a lower socio-economic status would receive a later diagnosis. Female subjects with a confirmed diagnosis of Rett syndrome were sourced from the Australian Rett Syndrome and InterRett Databases. Variables analyzed included timing and development of symptoms; MECP2 mutation type; parental occupation and education; maternal age and birth order. Residential location and socio-economic status were also analyzed for the Australian cases. Linear regression was used to determine relationships between these factors and age at diagnosis. A total of 909 cases were included. An older age of diagnosis was associated with later loss of hand function and speech, later onset of hand stereotypies and the presence of the p.R133C or p.R294X MECP2 mutation. Socio-economic factors did not predict age of diagnosis for Australian families. For families participating in the InterRett database, a younger age of diagnosis was associated with higher levels of parental education or occupation. A clinical picture consistent with the classic presentation of Rett syndrome is associated with an earlier diagnosis. Clinicians need to be alerted to the variable presentation of Rett syndrome including the milder phenotypes of cases with the p.R133C or p.R294X mutation. Educational resources to assist this understanding including guidance on when to request genetic testing could be useful to streamline the process of diagnosis in Rett syndrome. (c) 2010 Wiley-Liss, Inc.

2. Jellinger KA. {{The Neurochemical Basis of Autism: From Molecules to Minicolumns}}. {Eur J Neurol} (Aug 31)

3. O’Hearn K, Schroer E, Minshew N, Luna B. {{Lack of developmental improvement on a face memory task during adolescence in autism}}. {Neuropsychologia} (Aug 30)

Autism Spectrum Disorders (ASD) are associated with abnormalities in face memory, which evidence suggests has a protracted development through adolescence. The development of face memory in people with and without ASD, from 9 to 29 years old, was examined using the Cambridge Face Memory Test (CFMT). Results indicate that the developmental improvement evident from adolescence to adulthood typically was not apparent in individuals with ASD. While children and adolescents with ASD performed similarly to typically developing individuals comparable in age and IQ, adults with ASD displayed limitations on the CFMT. The pattern of performance was constant across conditions despite differences in the timing of the presentation and delay. This atypical development in ASD is consistent with the view that the processing of complex visual stimuli continues to develop through adolescence, along with the function and structure of the temporal lobes, but that this process is disrupted in ASD. This result underscores the importance of characterizing adolescent development for understanding ASD, and suggests additional opportunities for intervention.

4. Solt I, Bornstein J. {{[Childhood vaccines and autism–much ado about nothing?]}}. {Harefuah} (Apr);149(4):251-255, 260.

The increased diagnoses of autism and developmental disorders in recent decades, together with the childhood vaccination program, has led to the hypothesis that vaccination in general, and the measles, mumps, and rubella virus live vaccine, and vaccines that contain mercury, in particular, cause autism. It has been hypothesized that intestinal infection caused by live virus vaccines change the permeability of the intestinal wall, and subsequently, the passage of peptides through the intestinal wall to the blood, and from there to the brain. It has been suggested that the accumulation of these peptides in the central nervous system causes autism. Studies that investigated this theory did not find an association between vaccine administration and between digestive system symptoms and autism. According to a second hypothesis, an organomercury compound (Thimerosal), used as a preservative in vaccines that do not include live viruses, is a cause of autism. Like the former, this hypothesis has been well researched, and refuted. Some studies have in fact found an increase in autism diagnosis among children who were vaccinated after Thimerosal was removed from the vaccine preparation. Recent studies have refuted the theory that the consecutive administration of vaccines weakens the young immune system in children, and leads to an autoimmune process that causes autism. The etiology of autism is still unknown, with research continuing from different directions. The extensive research conducted so far indicates that childhood vaccination is not a cause of the sharp increase in autism diagnoses in recent decades.

5. Stein MT, Elias ER, Saenz M, Pickler L, Reynolds A. {{Autistic spectrum disorder in a 9-year-old girl with macrocephaly}}. {J Dev Behav Pediatr} (Sep);31(7):632-634.

CASE:: A 9-year-old girl was brought for consultation due to autism and a large head circumference. Her birth weight was 6 pounds after a 37-week gestation to a healthy G3P1SAb 2 mother. She had been a healthy child with the exception of the development of a lipomatous lesion on the left thigh, requiring surgical removal at age 3(1/2) years. Autism was diagnosed at age 5 yr by a developmental pediatrician. She did not have cognitive disabilities or a history of seizures. The family history was notable for maternal infertility with no history of developmental disabilities, large body or head size, or malignancy in close relatives.On physical examination, she was a mildly obese girl with a large head. Her weight was 50.4 kg (>95%), height was 142 cm (90%), and head circumference was 60.3 cm (significantly >95%; 4SDs above the mean). Examination of her skin was notable for a 2 x 6 cm scar on her left thigh and three cafe au lait macules on her trunk. She was Tanner Stage I. Mild hypotonia with normal deep tendon reflexes was observed; the remainder of the neurological examination was normal.Laboratory studies included high-resolution chromosomes, fragile X, metabolic screens, and methylation for Prader Willie Syndrome and Angelman Syndrome; all these studies were normal. Molecular testing of the PTEN gene (phosphatase and tensin homolog protein) revealed a R355X mutation, consistent with the diagnosis of Bannayan-Riley-Ruvalcaba Syndrome (BRRS). In parents and siblings, PTEN test results were negative for mutations.Endocrine evaluation revealed an abnormal thyroid nodule on ultrasound. Computed tomography and positron emission tomography scans raised suspicion of malignancy. She underwent a total thyroidectomy; the pathology report revealed a thyroid adenoma with Hurthle cells. She was treated with thyroid hormone replacement therapy.