Expressive Speech Delay Research Articles

Language and Cognitive Development of Children Who Have Williams Syndrome or Duplication of the Williams Syndrome Region

Language and Cognitive Development of Children Who Have Williams Syndrome or Duplication of the Williams Syndrome Region

Recurrent interstitial deletions of proximal 18q: A new syndrome involving expressive speech delay

Most deletions of the long arm of chromosome 18 involve some part of the most distal 30 Mb. We have identified five individuals with cytogenetically diagnosed interstitial deletions that are all proximal to this commonly deleted region. The extent of their deletions was characterized using molecular and molecular cytogenetic techniques. Each participant was assessed under the comprehensive clinical evaluation protocol of the Chromosome 18 Clinical Research Center. Three of the five individuals were found to have apparently identical interstitial deletions between positions of 37.5 and 42.5 Mb (18q12.3-->18q21.1). One individual's deletion was much larger and extended from a more proximal breakpoint position of 23 Mb (18q11.2) to a more distal breakpoint at 43 Mb (18q21.1). The fifth individual had a proximal breakpoint identical to the other three, but a distal breakpoint at 43.5 Mb (18q21.1). The clinical findings were of interest because the three individuals with the smaller deletions lacked major anomalies. All five individuals were developmentally delayed; however, the discrepancy between their expressive and receptive language abilities was striking, with expressive language being much more severely affected. This leads us to hypothesize that there are genes in this region of chromosome 18 that are specific to the neural and motor planning domains necessary for speech. Additionally, this may represent a previously underappreciated syndrome since these children do not have the typical clinical abnormalities that would lead to a chromosome analysis.

Terminal 22q deletion syndrome: a newly recognized cause of speech and language disability in the autism spectrum.

Cryptic subtelomeric chromosome rearrangements account for 6% to 10% of idiopathic mental retardation. As cytogenetic and molecular techniques have become more sophisticated, the number of genetic syndromes attributed to these microdeletions has increased. To date, 64 patients have been described in the literature with a more recently recognized microdeletion syndrome, del 22q13.3. The purpose of this study is to present 11 new cases of this recently described syndrome to delineate further the phenotype and to alert the clinician to another genetic condition that should be considered in the differential diagnosis of early hypotonia, delayed speech acquisition, and autistic behavior. Eleven patients were evaluated in 3 academic institutions. Clinical features and results of cytogenetic testing were recorded and tabulated. Reasons for referral for genetic evaluation included developmental delay, severe expressive speech and language delay, and dysmorphic features. Age of presentation ranged from 5 months to 46 years. There were 10 female patients and 1 male patient. All of the patients exhibited delayed motor development, some degree of hypotonia, and severe expressive speech and language delay. Dysmorphic facial features included epicanthal folds, large cupped ears, underdeveloped philtrum, loss of cupid's bow, and full supraorbital ridges. Six patients exhibited autistic-like behaviors. Microscopically visible chromosome deletions were observed in 6 patients. In the remainder, the deletion was detected with the use of fluorescence in situ hybridization. Hypotonia and developmental delay are nonspecific findings observed in many malformation and genetic syndromes. However, in association with severe speech and language delay and autistic-like behavior, this phenotype may be a significant indication to consider the 22q13 deletion syndrome as a potential cause.

X-linked creatine transporter defect: an overview.

In 2001 we identified a new inborn error of metabolism caused by a defect in the X-linked creatine transporter SLC6A8 gene mapped at Xq28 (SLC6A8 deficiency, McKusick 300352). An X-linked creatine transporter defect was presumed because of (1) the absence of creatine in the brain as indicated by proton magnetic resonance spectroscopy (MRS); (2) the elevated creatine levels in urine and normal guanidinoacetate levels in plasma, ruling out a creatine biosynthesis defect; (3) the absence of an improvement on creatine supplementation; and (4) the fact that the pedigree suggested an X-linked disease. Our hypothesis was proved by the presence of a hemizygous nonsense mutation in the male index patient and by the impaired creatine uptake by cultured fibroblasts. Currently, at least 7 unrelated families (13 male patients and 13 carriers) with a SLC6A8 deficiency have been identified. Four families come from one metropolitan area. This suggests that SLC6A8 deficiency may have a relatively high incidence. The hallmarks of the disorder are X-linked mental retardation, expressive speech and language delay, epilepsy, developmental delay and autistic behaviour. In approximately 50% of the female carriers, learning disabilities of varying degrees have been noted.

22q 13 Deletion Syndrome: A Genetic Basis For Neurobehavioral Disorders?

Neurobehavioral disorders pose a challenge to physicians, both in diagnostic and therapeutic aspects. Many neurobehavioral disorders have been identified to have a genetic basis such as the fragile X syndrome and the 22q11 deletion associated with the Velocardiofacial syndrome. We describe three children with a different and less well characterized deletion involving the most distal band of chromosome 22 (22q13), where the presentation entails deviant development, minor dysmorphism and autistic features.All 3 patients had developmental delay and unusual behavioral features. All our patients exhibited normal to advanced growth. Patient 1 had an added feature in submucous clefting of the palate. Patient 2 and 3 shared features of autistic spectrum disorder. Results of cytogenetic analysis in the three patients are as follows: Patient 1 ( 46XX ish del (22) (q13.3) (D22S39- D22S75X2), Patient 2 (46XY, del(22)(q13.1), Patient 3 (ish del (22)(q13q13) (LSI ARSA-) de novo). Thus, all three patients appear to share a deletion affecting the terminal 22q13 region.Literature review of the patients with 22ql3 deletion is presented. Initially, the deletion was detected using high resolution chromosome analysis. Recently a FISH probe (D22S39) through its fortuitous use as a control probe in testing for 22q11 deletions has been used to demonstrate this deletion. The phenotypic features in most of the cases described include marked expressive speech delay, deviant development and pervasive behaviors, minor motor delays, minor dysmorphism, with normal or exaggerated growth. While there remain gaps in our understanding of this particular deletion syndrome, we propose that patients with significantly delayed speech, deviant development and behavioral issues, and minor facial dysmorphism be screened for this deletion.