Pitt-Hopkins syndrome: report of a case with a TCF4 gene mutation

<p>Abstract</p> <p>Aims</p> <p>We will discuss the clinical and genetic diagnosis of a child with severe psychomotor delay, who at 3 years of age presented with paroxysms of hyperpnea-apnea and seizures unrelated to breathing anomalies.</p> <p>Methods</p> <p>The child underwent genetic (karyotype, FISH telomeres) and neuroradiological (cranial CT and MRI) tests, which proved to be normal. He came under our clinical observation at 3 years and 5 months of age. Due to severe psychomotor delay and facial dysmorphisms we completed the genetic investigations based on his clinical feature and analysis of the available literature.</p> <p>Results</p> <p>The presence of severe mental retardation associated with anomalous breathing pattern may suggest the Joubert and Rett syndrome, however these were excluded on the basis of clinical and genetic examination. Angelman syndrome, suspected for facial dysmorphisms and absent language, was also excluded because of the presence of a normal pattern of methylation at SNRPN locus. Another possible diagnosis was the Pitt-Hopkins Syndrome (PHS), characterized by severe mental retardation, breathing anomalies (paroxisms of hyperpnea-apnea), dysmorphisms and sometimes epilepsy. Haploinsufficiency of TCF4 gene located at 18q21.2 region has been recently identified as causative of this syndrome. In our patient the research of TCF4 mutation by the Institute of Human Genetics, University Hospital Erlangen (Germany), showed a de novo mutation.</p> <p>Conclusions</p> <p>The diagnosis of Pitt-Hopkins syndrome, an underdiagnosed cause of mental retardation, was based on clinical and genetic findings. Searching for TCF4 mutations is highly recommended when others overlapping syndromes was excluded. At our knowledge our patient is the first italian case of PHS diagnosed at molecular level.</p

Bartonella henselae infection associated with Guillain-Barri syndrome

This is the first report of Guillain-Barré syndrome (GBS) related to Bartonella henselae infection. A 10-year-old girl had difficulty walking and marked myalgia. The search for all causes known to trigger GBS was negative. She was treated with intravenous immunoglobulins and recovered. Because she lived in a rural area and had a history of kitten contact, a specific serology for B. henselae infection was performed and confirmed an ongoing infection. She did not show any clinical typical feature of cat-scratch disease. B. henselae infection should be considered in the wide etiologic spectrum of GBS. © 2005 Lippincott Williams & Wilkins

A rare case of hypomelanosis of Ito presenting with generalized alopecia

A rare case of hypomelanosis of Ito presenting with generalized alopeci

Clinical pattern, mutations and in vitro residual activity in 33 patients with severe 5, 10 methylenetetrahydrofolate reductase (MTHFR) deficiency

Background Severe methylenetetrahydrofolate reductase (MTHFR) deficiency is a rare inborn defect disturbing the remethylation of homocysteine to methionine ( Methods Clinical, biochemical and treatment data was obtained from physicians by using a questionnaire. MTHFR activity was measured in primary fibroblasts; genomic DNA was extracted from cultured fibroblasts. Results Thirty-three patients (mean age at follow-up 11.4 years; four deceased; median age at first presentation 5 weeks; 17 females) were included. Patients with very low (1.7-34.8 %) residual enzyme activity had mainly psychiatric symptoms, mental retardation, myelopathy, ataxia and spasticity. Treatment with various combinations of betaine, methionine, folate and cobalamin improved the biochemical and clinical phenotype. During the disease course, patients with very low enzyme activity showed a progression of feeding problems, neurological symptoms, mental retardation, and psychiatric disease while in patients with higher residual enzyme activity, myelopathy, ataxia and spasticity increased. All other symptoms remained stable or improved in both groups upon treatment as did brain imaging in some cases. No clear genotype-phenotype correlation was obvious. Discussion MTHFR deficiency is a severe disease primarily affecting the central nervous system. Age at presentation and clinical pattern are correlated with residual enzyme activity. Treatment alleviates biochemical abnormalities and clinical symptoms partially