In adults, the syndrome may occur after a stroke or in association with damage to the parietal lobe. In addition to exhibiting the above symptoms, many adults also experience aphasia, which is a difficulty in expressing oneself when speaking, in understanding speech, or in reading and writing.

There are few reports of the syndrome, sometimes called developmental Gerstmann syndrome, in children. The cause is not known. Most cases are identified when children reach school age, a time when they are challenged with writing and math exercises. Generally, children with the disorder exhibit poor handwriting and spelling skills, and difficulty with math functions, including adding, subtracting, multiplying, and dividing. An inability to differentiate right from left and to discriminate among individual fingers may also be apparent. In addition to the four primary symptoms, many children also suffer from constructional apraxia, an inability to copy simple drawings. Frequently, there is also an impairment in reading. Children with a high level of intellectual functioning as well as those with brain damage may be affected with the disorder.

There is no cure for Gerstmann syndrome. Treatment is symptomatic and supportive. Occupational and speech therapies may help diminish the dysgraphia and apraxia. In addition, calculators and word processors may help school children cope with the symptoms of the disorder.

In adults, many of the symptoms diminish over time. Although it has been suggested that in children symptoms may diminish over time, it appears likely that most children probably do not overcome their deficits, but learn to adjust to them.

The National Institute of Neurological Disorders and Stroke (NINDS) supports research on disorders that result from damage to the brain such as dysgraphia. The NINDS and other components of the National Institutes of Health also support research on learning disabilities. Current research avenues focus on developing techniques to diagnose and treat learning disabilities and increase understanding of the biological basis of them.

This disorder is often associated with brain lesions in the dominant (usually left) side of the angular and supramarginal gyri near the temporal and parietal lobe junction.

It should not be confused with Gerstmann-Straussler syndrome, which is a transmissible spongiform encephalopathy.

Organizations

Learning Disabilities Association of America
4156 Library Road Suite 1
Pittsburgh, PA 15234-1349

Tel: 412-341-1515 412-341-8077
Fax: 412-344-0224

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Evidence that the 127-164 region of prion proteins has two equi-energetic conformations with (beta) or (alpha) features
From Biophysical Journal, 9/1/01 by Derreumaux, Philippe

ABSTRACT Prion proteins cause neurodegenerative illnesses in humans and animals. The diseases are associated with a topological change from a predominantly alpha (PrP^sup c^) to gamma-sheet (PrP^sup sc^) structure. Many studies have focused on the minimum sequence requirements and key events for developing or transmitting disease. Here, we report on the application of molecular modeling studies to predict the lowest-energy conformations for five fragments in solution at pH 7. We show that PrP(143-- 158) adopts a helix, the model PrP(106-126), PrP(142-167), and PrP(143-178) peptides have a clear preference for a variety of beta-sheet structures, whereas PrP(127-164) has two iso-energetic conformations with all beta or alphabeta native-like structures. Such a finding for PrP(127-164), which explains a large body of experimental data, including the location of all mutations causing prion diseases, may have important implications for triggering or propagating the topological change.

INTRODUCTION

In summary, we have shown that both PrP(106-126) and PrP(127-164) are prone to form scrapie-like beta structures. In contrast to PrP(106-126) and previous model peptides studied (Derreumaux, 1999, 2000), which are predicted to be in equilibrium between their native topologies and random coil conformations, PrP(127-164) is found to code for two distinct topologies with comparable energies in isolation. Because strand S2 interacts with helices H2 and H3, the extrapolation of this energetic result to the behavior of the full PrP protein in vivo remains to be validated. Nevertheless, this conformational distribution clarifies a large body of experimental aspects and provides a simple explanation for propagating and/or triggering the PrP topological change.

I am indebted to Serguei Kozin for providing me with the NMR structure of mPrP(142-167) and for numerous discussions. I also thank Pascale Debey, Vincent Monchois, Yves-Henri Sanejouand, and the anonymous referees for helpful comments.

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Philippe Derreumaux

Information Genetique et Structurale, CNRS-UMR 1889, 13402 Marseille, France

Received for publication 31 January 2001 and in final form 14 May 2001.

Address reprint requests to Dr. Philippe Derreumaux, Information Genetique et Structurale, CNRS-UMR 1889, 31 Chemin Joseph Aiguier, 13402 Marseille, France. Tel.: 33-4-91164603; Fax: 33-4-91164549; E-mail: philippe@igs.cnrs-mrs.fr.

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