'Cap myopathy': case report of a family.

We report the observation of an 18-year-old girl, whose clinical presentation was very suggestive of a congenital myopathy with neonatal onset. A congenital myopathy had been already diagnosed in her brother and in addition her half-cousin died diagnosed with a severe nemaline myopathy at age 4 years. A muscle biopsy performed on both siblings revealed histological and ultrastructural features of 'cap myopathy'. This case report suggests that 'cap myopathy' and some cases of nemaline myopathy with neonatal onset might be two phenotypic expressions of the same genetic disorder. These two entities could therefore, perhaps, be regarded as 'Z-line disorders' possibly caused by defective myofibrillogenesis.

Congenital muscular dystrophy with primary partial laminin alpha2 chain deficiency: molecular study.

The authors report a case of congenital muscular dystrophy with mild nonprogressive muscle weakness, white matter hypodensity, and absence of the laminin alpha2 chain in muscle fibers with two antibodies, but not with four others. They identified mutations in LAMA2, which explain the partial laminin alpha2 deficiency. Analysis of this case and two others allows us to refine the epitopes of two of the commercial antibodies, and illustrate the importance of using antibodies directed against different domains of the protein.

Homogeneous phenotype of the gypsy limb-girdle MD with the gamma-sarcoglycan C283Y mutation.

OBJECTIVE: To characterize the clinical phenotype of LGMD2C in gypsies. BACKGROUND: Limb-girdle muscular dystrophy (LGMD) in gypsies of Western Europe is caused by a homozygous C283Y mutation on the same haplotype, suggesting a founder effect. METHODS: We performed clinical, laboratory, and muscle imaging studies of 40 patients. RESULTS: Mean age at onset was 5.3 years. One half of the patients had loss of ambulation by the age of 12; 13% still could walk after age 16. Calf hypertrophy, scapular winging, macroglossia, and lumbar hyperlordosis were common. Girdle, trunk, and proximal limb flexor muscles had earlier and more severe involvement. Cardiomyopathy was not observed. Five patients in the third decade of life required mechanical ventilation. Scoliosis was common in the nonambulatory stage. CONCLUSIONS: LGMD2C in gypsy patients with C283Y mutation presents a rather homogeneous phenotype, characterized by an initial Duchenne-like progressive course followed by a more prolonged survival rate possibly due to the absence of early respiratory impairment and cardiac failure.

Genetic heterogeneity of congenital muscular dystrophy with rigid spine syndrome.

Rigid spine syndrome is a neuromuscular disorder characterised by early rigidity of the spine due to axial muscle contractures, generally associated with muscle weakness, limb-joint contractures, and often respiratory failure. This phenotype may be associated with several muscular diseases. In cases of merosin-positive congenital muscular dystrophies (CMD) with rigid spine syndrome, we have recently identified a new locus (RSMD1) on chromosome 1p35-36. In the present study, we report the clinical, morphological and genetic analysis of other patients affected by a CMD with rigid spine syndrome from nine consanguineous families. Homozygosity mapping showed that the disease was linked to RSMD1 in one of the nine families. The other families were excluded from RSMD1, and the patients presented highly variable phenotypes suggesting the involvement of more than one gene defect in rigid spine syndrome. Nevertheless, a subgroup of patients who never walked, and had very early rigidity of the spine and scoliosis, may be considered for further genetic analysis.

Genetics of laminin alpha 2 chain (or merosin) deficient congenital muscular dystrophy: from identification of mutations to prenatal diagnosis.

Congenital muscular dystrophies (CMD) are a clinically and genetically heterogeneous group of muscle disorders, with autosomal recessive inheritance. Absence of the laminin alpha 2 chain in the skeletal muscle of patients with classical CMD has permitted the identification of a subgroup, referred to as 'merosin-deficient CMD or laminin alpha 2 chain deficient CMD'. We first identified a nonsense and a splice site mutation in laminin alpha 2 gene (LAMA2) (Glu1241 stop, 4573-2A-->T). We report here new mutations: nonsense mutations (Glu210stop, Trp2316stop) and 1- and 2-bp deletions (2418 delta C, 6968 delta TA), which result in truncation of the protein either in the short arm domains or in the C terminal globular domain and complete merosin deficiency. Another subgroup, referred to as 'partially-deficient in laminin alpha 2 chain' has been identified recently, and a LAMA2 missense mutation (Cys996Arg) has been shown to cause this partial deficiency. The laminin alpha 2 chain, together with the beta 1 or beta 2 and gamma 1 chains forms either laminin-2 (alpha 2-beta 1-gamma 1) or laminin-4 (alpha 2-beta 2-gamma 1). The LAMA2 mutations induce the formation of abnormal laminins which probably dramatically disturb the assembly and stability of the laminin network, one of the major components of the extracellular matrix in skeletal muscle. We report also the first prenatal diagnosis performed by direct mutation analysis.

Brown-Vialetto-Van Laere syndrome in a large inbred Lebanese family: confirmation of autosomal recessive inheritance?

Brown-Vialetto-Van Laere syndrome or pontobulbar palsy with deafness is a rare disorder characterized by bilateral nerve deafness, a variety of cranial nerve disorders usually involving the motor components of the 7th and 9th to 12th cranial nerves, and less commonly an involvement of spinal motor nerves and upper motor neurons. Familial and sporadic cases have been reported. Based on particular evidence, autosomal recessive, autosomal dominant, and X-linked inheritance, as well as autoimmune origin have been considered. We report on a large inbred Lebanese family with four patients of both sexes, strongly suggesting autosomal recessive inheritance.

Thoracoabdominal pattern of breathing in neuromuscular disorders.

STUDY OBJECTIVE: To assess abnormalities in thoracoabdominal pattern of breathing (TAPB) in neuromuscular disorders during spontaneous breathing, intermittent positive pressure ventilation (IPPV) with and without abdominal (AB) binder, and immediately after IPPV. DESIGN: Repeated measures design: Pre-IPPV spontaneous breathing, IPPV, IPPV with AB binder, and post-IPPV spontaneous breathing. In protocol 1, ventilator pressure was held constant at the individual value habitually adopted in sessions of IPPV. In protocol 2, it was increased stepwise from 5 to 30 cm H2O. SETTING: University hospital, Department of Pediatrics, Intensive Care, and Neuro-Ventilatory Rehabilitation. PATIENTS: Thirty-one patients with spinal muscular atrophy (SMA) and 19 patients with myopathy, mean age (+/- SD) 9.7 +/- 3 years. MEASUREMENTS: Tidal volume (VT), percent thoracic contribution to VT (%RC), the phase angle between the thoracic and the AB volume changes and the labored breathing index, which is an index of asynchrony taking into account both the phase relationships and relative volumes of rib cage and AB compartments. RESULTS: We observed marked abnormalities in TAPB during spontaneous breathing, especially in the SMA group. %RC, labored breathing index, and phase angle displayed nearly normal values during IPPV. IPPV pressures of 25 to 30 cm H2O were necessary to increase %RC above 80%. AB binding decreased VT, but led to larger thoracic volumes, especially in patients with SMA. Thoracic contribution to VT and thoracic volume after IPPV were higher than baseline levels. CONCLUSIONS: The quantitative assessment of TAPB enhances the ability to estimate pulmonary function in neuromuscular disorders, and the efficiency of mechanical ventilation.

Treatment of mediastinitis in children after cardiac surgery. A study of 20 cases.

Twenty-three cases of mediastinitis after cardiac surgery in children were treated by us between 1973 and 1976. Three patients died within 6 hours of admission. Treatment used in the tweny other cases are discussed. The mean age of the patients was three years and three months. The mediastinitis was evident an average of twelve days after extracoporeal circulation. A staphylococus was always responsible for the infection. Treatment was a combination of surgery, antibiotics and respiratory and nutritional supplies. The surgical treatment consisted of a careful mediastinal cleansing with resection of the sternal edges. In fifteen patients the thorax was closed after surgery, and an irrigation system installed using a solution of 4% Dakin in physiologic saline. Recovery was simple in 5 patients. In the 10 other patients of this group the thorax had to be reopened; one patient died after 90 days from Serratia marcescens endocarditis. The thorax was left open initially in five patients: one patient of this group died from candida endocarditis. All patients needed endotracheal ventilation through a nasotracheal tube (7 to 90 days of ventilation). Treatment with bactericidal antibiotics was pursued for three months and a monotherapy was kept for nine months. After reviewing the observed complications, our methods and results are compared with others in the literature.

Membrane oxygenators for acute respiratory insufficiency. Clinical use in 11 patients.

Extracorporeal circulation with a membrane oxygenator (ECMO) was used in 11 patients with acute respiratory insufficiency who did not respond to conventional treatment. By pass was veno-arterial in every case, seven times with femoral artery return, three times with axillary artery return, and once with both femoral and axillary return. Five patients died on ECMO. Six patients were taken off ECMO and two of them are long-term survivors. In nine cases ECMO allowed short-term control of respiratory failure. The respective roles of oxygen supply from ECMO and the haemodynamic changes incurred by its use are discussed. Although use of ECMO for long periods seems less hazardous now, present results are restricted by the lack of therapy for the underlying pulmonary lesions.

Diaphragmatic paralysis in children: a review of 11 cases.

We reviewed 11 pediatric cases of diaphragmatic paralysis related to nonspinal-cord injury which were managed in our Intensive Care Unit over the past 10 years. Three cases were secondary to birth trauma, 7 followed surgical procedures for congenital heart disease, and 1 occurred in association with injuries sustained in a motor vehicle accident. The paralysis was bilateral in 8 children. The diagnosis was initially suspected on clinical grounds because of respiratory distress, impossibility of weaning from the ventilator, and paradoxical abdominal respiratory movements. Confirmatory investigations included chest radiography, which revealed elevation of the affected hemidiaphragm, fluoroscopy and ultrasound, both of which demonstrated diminished diaphragmatic movement. Electromyography exhibited a failure of diaphragmatic response to phrenic nerve stimulation in 8 patients. All patients were mechanically ventilated; tracheostomy was required in 5 patients. Physiotherapy was considered a beneficial adjuvant measure. Diaphragmatic plication was attempted without success in 3 children. Seven children recovered without sequelae: Partial respiratory autonomy was achieved after an average of 2.6 months, complete autonomy after an average of 5.4 months. Two patients developed chronic lung disease; one of them remains unresponsive, and one child died following accidental extubation. We conclude that the diagnosis of diaphragmatic paralysis is predominantly clinical, and that the outcome of patients treated by adequate endotracheal mechanical ventilation is usually favorable.

[Dysautonomia in acute primary polyradiculoneuritis]. / La dysautonomie des polyradiculonévrites aiguës primitives

In this research involving 172 cases of acute primary polyradiculoneuritis, the authors draw attention to the frequency and seriousness of the autonomic disorders, notably circulatory disorders (arterial hypertension, bradycardia), water retention, disorders in glucose metabolism. They have found a close correlation between the development of arterial hypertension and levels of VMA and the cathecholamines and between the appearance of hyperglycaemia and the level of urinary 17 OH. Free water clearance is often negative and becomes positive as the paralytic syndrome improves. The biological picture is identical with that brought about by inappropriate secretion of HAD. From the therapeutic point of view, caution is advised in using certain procedures and in prescribing certain drugs.

[The Landry-Guillain-Barré syndrome. Study of prognostic factors in 223 cases]. / Le syndrome de Landry-Guillain-Barré. Etude des facteurs pronostiques dans 223 cas.

A retrospective study of 223 patients (111 men, 112 women, mean age 40.6 years) with the Landry-Guillain-Barre syndrome investigated vital or functional prognostic factors. Patients were first seen between 1963 and 1981, when 192 were noted to have cranial nerve disorders. Assisted ventilation was required in 152 cases, and 23 patients died, including 5 from cardiocirculatory dysautonomy. Plasma exchange was not used. Patients were divided into 3 groups as a function of the degree of maximum paralysis: group 1 (n = 63) patients had incomplete quadriplegia without assisted ventilation, group 2 (n = 93) incomplete quadriplegia with assisted ventilation, group 3 (n = 62) quadriplegia with or without assisted ventilation. Vital prognosis was related to the severity of neurologic disorders. Frequency of intercurrent complications, dysautonomic disorders and mortality increased with maximal severity of motor deficit. The 3 groups did not differ as a function of previous history, mode of onset of polyradiculoneuritis, duration of extension phase of paralysis, or CSF protein content at the first examination during the extension phase of the paralyses. It is therefore impossible at an early stage of the disease to predict future motor deficit. The cumulative percentage of patients who recovered a normal muscular force in limbs and cranial territories was 48 p. 100 after one year and 60 p. 100 after two years (actuarial values). The functional prognosis depends upon the degree of motor deficit at maximum paralysis and duration of the plateau phase. Probability of full muscular strength recovery was lower in group 3 and in those patients with a plateau phase duration longer than 2 weeks. Independently of groups, motility recovery rate was markedly higher in patients with a plateau phase duration of less than one week. Motility recuperation was independent of age, sex, duration of extension phase, CSF protein levels during the acute phase, and presence of autonomic nervous system disorders.

[Infantile spinal muscular atrophy]. / Amyotrophie spinale infantile.

The authors report 100 cases with prolonged spinal muscular atrophy (SMA) and survival beyond 4 years old. There were 46 boys and 54 girls. 23 of them had histories with an autosomal recessive form of inheritance. One case had a dominant form. The unity of cases described as Werdnig Hoffman disease [SMA I, SMA II (Childhood), ans SMA III (Kugelberg Welander)] is supported and our cases fell in three groups according to their ambulatory capabilities: never acquired, lost, or retained. 71 cases have never walked: the onset of symptoms was noted at an average age of 6.4 months +/- 3; the average age at the last examination was 16 years (4-39). Death occurred in 6 cases. Loss of walking occurred in 24 cases: the onset of symptoms was noted at an average age of 17.4 months +/- 14.2. 5 cases were still ambulatory: the onset of symptoms was noted at an average age of 2.4 years +/- 2.8. For these last 29 cases the average age at the last examination was 20 years (4-38); death occurred in two cases. The weakness was symmetrical and proximal. The period of worsening varied but, frequently, patients with a later onset of symptoms had a longer period of deterioration. Tongue fasciculations were present in all cases who never walked. Facial and masseter weakness occurred in 3 cases. Oesophagus dyskinesia and distension of the stomach due to brain stem lesions occurred in many cases. This brain stem damage was responsible of 2 sudden deaths (8-30 years). Premature puberty occurred in 14 cases.(ABSTRACT TRUNCATED AT 250 WORDS)

[Familial mitochondrial encephalopathy. A clinicopathologic study]. / Encéphalopathie mitochondriale familiale. Etude clinicopathologique.

We report the cases of 2 siblings with progressive encephalopathy. The first symptoms were noted when they were 6 years old. The full clinical picture included myoclonus, seizures, cerebellar ataxia, blindness due to optic atrophy and retinal degeneration, deafness, swallowing difficulties with relatively spared intellectual functions. The course was progressive and led to death within 8 years. The pathological findings included bilateral and almost symmetrical lesions involving the thalami, the colliculi, and the pontine and medullar tegmentum, similar to the changes described in Leigh disease. Neuronal loss and gliosis were noted in the dentate nucleus and in the inferior olive, as in MERRF syndrome. Laminar necrosis of the cerebral cortex could have been due to episodes of severe hypotension before death. Cytochrome c oxidase deficiency was found in case 2. The enzyme deficiency was present in muscle and in fibroblasts in culture.

[Andermann syndrome in an Algerian family: suggestion of phenotype and genetic homogeneity]. / Le syndrome d'Andermann dans une famille algérienne: suggestion d'une homogénéité phénotypique et génétique.

Andermann syndrome or Agenesis of the Corpus Callosum with Polyneuropathy (MIM 218000) is an autosomal recessive disease almost exclusively found in Québec. Only few cases have been reported in other populations. The locus for Andermann syndrome was assigned to chromosome 15q13-q15 in French Canadian families. We performed a haplotype analysis with two markers of this chromosomal region in an Algerian consanguineous family with two affected sibs. The children were homozygous for both markers, suggesting genetic homogeneity in Andermann syndrome.

[Congenital myasthenic syndromes due to mutations in the rapsyn gene]. / Syndromes myasthéniques congénitaux dus à des mutations du gène de la rapsyne.

Congenital myasthenic syndromes (CMS) are genetic diseases characterized by dysfunctional neuromuscular transmission and usually start during the neonatal period. Most are due to postsynaptic abnormalities, specifically to mutations in the acetylcholine receptor (AChR) genes. In 2002, the group of A Engel reported the first cases of CMS with mutations in the gene coding rapsyn, a postsynaptic molecule which stabilizes AChR aggregates at the neuromuscular junction. Since this first publication, more than 30 other cases, including six in France, have been reported. Study of these published cases allows us to distinguish three classes of phenotypes: 1) severe neonatal cases; 2) more benign cases, starting during infancy; 3) cases with facial malformations, involving Jewish patients originating from the Near-East. Comparison of the observations of other groups with our own has led us to the following conclusions: the N88K mutation is frequent (homozygous in 50% of cases); besides the N88K mutation, the second mutation varies considerably; heterozygous allelic cases (N88K + another mutation) are severe; there is probably a founder effect in the European population. There is phenotypic variability in the homozygous N88K cases, with benign cases and severe cases of early expression. A Engel and colleagues report that the seven cases of benign CMS with facial malformation, previously described in the Jewish population of Iraq and Iran, were caused by mutation in the promoter region of the rapsyn gene.

[Congenital muscular dystrophy with merosin deficiency: clinical, histopathological, immunocytochemical and genetic analysis]. / Dystrophie musculaire congénitale avec déficience en mérosine: analyse clinique, histopathologique, immunocytochimique et génétique.

A selective deficiency of a specific laminin isovariant, merosin made of M, B1 and B2 chains, was found in a series of 17 patients affected with congenital muscular dystrophy (CMD). The merosin deficiency was complete in 15 cases, and almost complete in two cases. An overexpression of the laminin A chain was seen in these biopsies, while B1 and B2 chains were normally expressed. Comparison of the clinical data with a series of 18 "merosin-non deficient" cases showed that the "merosin-deficient" cases were forming a more homogenous group than the "non-deficient" one. Hypotonia, contractures, motor development delay were generally more severe in the "merosin-deficient" series of cases. Moreover, white matter alterations were seen in most cases explored by MRI or scan imaging. A genetic linkage with a 6q2 locus, corresponding to the M chain gene localization, was found in a panel of informative families from French and Turkish origin with "merosin deficient" CMD. "Merosin non-deficient" families did not map on this locus. So, the "merosin-deficient" CMD can be considered as a peculiar entity within the group of Congenital Muscular Dystrophies.

[Ventricular staphylococcal infections. Treatment with vancomycin by continuous venous infusion]. / Infections ventriculaires à staphylocoque. Traitement par la vancomycine en perfusion veineuse continue.

Thirteen cases of meningeal and/or ventricular infection and 1 case of septicaemia, all caused by staphylococci, were treated with continuous intravenous infusions of vancomycin. Repeated measurements of vancomycin plasma and CSF levels by microbiological assay or by high performance liquid chromatography showed that the antibiotic entered the CSF after 48 hours of treatment and that its concentrations in CSF remained stable at 1 to 4 micrograms/ml (mean: 2 micrograms/ml) throughout the 3 weeks' treatment period. After treatment was discontinued, vancomycin became undetectable in CSF within less than 24 hours. All the children were cured.

[Thoracic scoliosis: exothoracic and endothoracic deformations and the spinal penetration index]. / Scolioses thoraciques: les gibbosités exo et endo thoraciques et l'index de pénétration rachidienne.

PURPOSE OF THE STUDY: We reviewed retrospectively our patients with thoracic lordoscoliosis and conducted a conceptual analysis of the patients with airway compression and atelectasia due to anterior protrusion of the vertebral bodies in order to describe the pathological conditions involved and the management methods used. Our goal was to develop a new concept for quantifying thoracic deformation. The individual cases discussed here have been reported earlier, but this is the first series analysis to date. MATERIAL AND METHODS: Eighteen patients, aged 7.3 to 18 years, with thoracic lordoscoliosis due to a variety of causes, mostly neuromuscular disorders (12 cases), are described. Most patients were treated by anterior subtotal periosteal resection of the vertebral body followed by posterior instrumentation and arthrodesis. RESULTS: Atelectasia disappeared with a normalization of blood gases but the effect was variable on vital capacity. The analysis of the CT studies led to the concept of spinal deformity as an endothoracic deformation resulting from protrusion of the vertebral body into the thorax, the endothoracic vertebral hump. This concept was developed and quantified leading to the definition of a new index: the spinal penetration index. The spinal penetration index was obtained by tracing a line tangent to the posterior curve of the concave and convex ribs on each CT slice to determine a relationship between the real thoracic surface and theoretical thoracic surface measured with this tangent and the circumference of the thoracic cage. The index was expressed as a percent of the endothoracic surface occupied by the protruding veterbral body and the associated ribs. Calculated for each successive CT slice for the entire height of the thorax yielded a spinal penetration index quantifying the thoracic volume occupied by the spine. For the control population, we used CT series of the thorax obtained to search for pulmonary metastases in patients with malignant tumors. This gave a theoretical volume of 8 to 10% occupied by the spine in normal subjects. In our patients with lordoscoliotic deformations we obtained real volumes of 15, 20 and even 50%. DISCUSSION: The spinal penetration index is an important morphological index of thoracic anatomy that measures the real volume of the functional thoracic cavities and which must be differentiated from vital capacity which measures both volume and function. This index can be used for pre- post-operative comparisons and constitutes a first step in 3-D assessment of thoracic spine deformations. It can also be used to classify spinal deformations and to make general recommendations concerning the management of both endothoracic humps and exothoracic rib humps.

[Respiratory problems in severe scoliosis]. / Les problèmes respiratoires des scolioses graves.

In kyphoscoliosis restrictive ventilatory defect occurs. In idiopathic scoliosis vital capacity failure is significantly correlated with Cobb angle, vertebral rotation, and thoracic lordosis. Maximum voluntary ventilation is the most affected measurement. Forced expiratory volume in 1 second is reduced. Residual volume remains longtime normal. Hypoxemia due to decrease of diffusing capacity occurs, with initially reflex hyperventilation hypocapnia, and secondary hypercapnia. Pulmonary hypertension and cor pulmonale is related to hypoventilation and hypoxia. The lung situated on the concave side of the scoliosis curve shows a more functional derangement. Ventilatory pattern consists of low tidal volume and high respiratory rate with increase of ventilatory work. Scoliosis that appears in the earlier stage of the life has the worst respiratory prognosis (before 5 years of age) with impairement of lung and thoracic growth. To stimulate pulmonary and thoracic growth, intermittent ventilatory assistance by pressure preset ventilator should be performed as soon as possible and pursued up to 8 years of age, at least, more if necessity. In over 60 degrees angle idiopathic scoliosis, respiratory failure appears after 40 to 50 years of age. Non invasive ventilatory assistance with preset pressure ventilator by oral way in moderate cases and nocturnal nasal ventilation by volume ventilator or inspiratory assistance ventilator, in the most severe cases are efficient. In very severe and acute respiratory insufficiency (scoliosis over 90 degrees) ventilation by intubation then tractheostomy may be required. Earlier orthopedic management and surgical procedure to correct and stabilize spinal deformities is the best to prevent respiratory insufficiency. For scoliosis below 60 degrees, post operative pulmonary complications are very low, with no requirement of post operative ventilatory support. In very severe respiratory insufficiency treatment of respiratory failure precedes, and follows, orthotic treatment and surgical procedures; it shouldle pursued afterwards.