Hereditary neuropathy with liability to pressure palsy presenting with hand drop in a young child.

Hereditary neuropathy with liability to pressure palsy (HNPP) results from the deletion of the PMP22 gene in chromosome 17p11.2. Clinically, it presents with painless pressure palsies, typically in the 2nd and 3rd decades of life, being a rare entity in childhood. We present the case study of a six-year-old male child who presented with left hand drop that he kept for over four weeks. Electrophysiological studies suggested HNPP and genetic studies confirmed it. With this paper, we pretend to create awareness to this entity as a diagnosis to be considered in a child with painless monoparesis and to emphasize the importance of electrophysiological studies in the diagnosis.

[Spinal muscular atrophy: descriptive analysis of a case series]. / Atrofia muscular espinhal: análise descritiva de uma série de casos.

INTRODUCTION: Spinal Muscular atrophy (SMA) is a genetically determined specific neuromuscular disease, characterized by the deterioration of spinal a motor neurons, causing progressive muscular atrophy and weakening. It is genetically determined, with the absence or mutation of the survival motor neuron 1 (SMN1) as a hallmark. A similar copy of the SMN1, named SMN2, modulates the severity of the disease. Several types of the disease have been described along with several classification systems based either on the age at onset of symptoms or on the maximum function achieved. SMA leads to a vast group of secondary manifestations in various organ systems, particularly the respiratory, muscle-skeletal and gastrointestinal. GOAL: To study the population with the diagnosis of SMA (clinical and/or genetic) followed in the Physical Medicine and Rehabilitation outpatient clinic (PMR) of the Hospital de Dona Estefânia (HDE) in Lisbon, from January 2007 to October 2009. METHODS: The authors conducted a retrospective study focusing on socio-demographic, clinical parameters, evolution and complications of the disease. RESULTS AND DISCUSSION: Twelve children were enrolled in the study, with age ranging from 0 months to 21 years, four diagnosed with SMA type III, seven with SMA type I and one with SMA II. An inverse relation was found between the severity of the course of illness and the age at onset and maximum motor function achieved. All patients sustained recurrent lower respiratory infections during the course of the disease. Respiratory insufficiency complicated by cardio-respiratory arrest was the cause of death in the deceased patients. The main musculoskeletal complication was the development of contractures in the main joints of the lower limbs, as well as scoliosis. Dysphagia was the main gastroenterological complication. CONCLUSION: The authors conclude that the lack of acquisition of motor developmental milestones is correlated to worse vital and functional prognosis.

Phenotypical spectrum of DOK7 mutations in congenital myasthenic syndromes.

Dok ('downstream-of-kinase') family of cytoplasmic proteins play a role in signalling downstream of receptor and non-receptor phosphotyrosine kinases. Recently, a skeletal muscle receptor tyrosine kinase (MuSK)-interacting cytoplasmic protein termed Dok-7 has been identified. Subsequently, we and others identified mutations in DOK7 as a cause of congenital myasthenic syndromes (CMS), providing evidence for a crucial role of Dok-7 in maintaining synaptic structure. Here we present clinical and molecular genetic data of 14 patients from 12 independent kinships with 13 different mutations in the DOK7 gene. The clinical picture of CMS with DOK7 mutations is highly variable. The age of onset may vary between birth and the third decade. However, most of the patients display a characteristic 'limb-girdle' pattern of weakness with a waddling gait and ptosis, but without ophthalmoparesis. Respiratory problems were frequent. Patients did not benefit from long-term therapy with esterase inhibitors; some of the patients even worsened. DOK7 mutations have emerged as one of the major genetic defects in CMS. The clinical picture differs significantly from CMS caused by mutations in other genes, such as the acetylcholine receptor (AChR) subunit genes. None of the patients with DOK7 mutations had tubular aggregates in the muscle biopsy, implying that 'limb-girdle myasthenia (LGM) with tubular aggregates' previously described in literature may be a pathogenic entity distinct from CMS caused by DOK7 mutations.