Clinical correlations and long-term follow-up in 100 patients with sarcoglycanopathies.

BACKGROUND AND PURPOSE: To describe a large series of patients with α, ß, and γ sarcoglycanopathies (LGMD-R3, R4, and R5) and study phenotypic correlations and disease progression. METHODS: A multicentric retrospective study in four centers in the Paris area collecting neuromuscular, respiratory, cardiac, histologic, and genetic data. The primary outcome of progression was age of loss of ambulation (LoA); disease severity was established according to LoA before or after 18 years of age. Time-to-event analysis was performed. RESULTS: One hundred patients (54 γ-SG; 41 α-SG; 5 ß-SG) from 80 families were included. The γ-SG patients had earlier disease onset than α-SG patients (5.5 vs. 8 years; p = 0.022) and ß-SG patients (24.4 years). Axial muscle weakness and joint contractures were frequent and exercise intolerance was observed. At mean follow-up of 22.9 years, 65.3% of patients were wheelchair-bound (66.7% α-SG, 67.3% γ-SG, 40% ß-SG). Dilated cardiomyopathy occurred in all sarcoglycanopathy subtypes, especially in γ-SG patients (p = 0.01). Thirty patients were ventilated and six died. Absent sarcoglycan protein expression on muscle biopsy and younger age at onset were associated with earlier time to LoA (p = 0.021 and p = 0.002). Age at onset was an independent predictor of both severity and time to LoA (p = 0.0004 and p = 0.009). The α-SG patients showed genetic heterogeneity, whereas >90% of γ-SG patients carried the homozygous c.525delT frameshift variant. Five new mutations were identified. CONCLUSIONS: This large multicentric series delineates the clinical spectrum of patients with sarcoglycanopathies. Age at disease onset is an independent predictor of severity of disease and LoA, and should be taken into account in future clinical trials.

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.

Jeune syndrome and liver disease: report of three cases treated with ursodeoxycholic acid.

Three children with Jeune syndrome (asphyxiating thoracic dystrophy) had clinical and laboratory evidence of liver disease. In two patients the disease evolved to biliary cirrhosis, whereas in the third it was recognized when extensive fibrosis was developing. In the three patients, treatment with ursodeoxycholic acid appeared to control the progression of the hepatic dysfunction.

Sleep disorders caused by brainstem tumor: case report.

Few studies concerning sleep disorders in brainstem lesions or tumors have been published. We report the case of a girl who was operated on for a brainstem tumor at the age of 4 years. In postsurgery, she had hemiparesis of the left side, swallowing difficulties, and severe apneas requiring a tracheotomy with nocturnal ventilation. The child's health improved progressively. Two sleep recordings were performed at 7 and 9 years without nocturnal ventilation. These recordings showed sleep disorders with a decrease in total sleep time and rapid eye movement (REM) sleep. Several central apneas were observed. The apneas were more frequent during REM sleep in the first recording and were associated with desaturation and microarousals.

[Chylothorax complicating a subclavian puncture controlled by positive-pressure expiratory ventilation]. / Chylothorax compliquant une ponction sous-clavière contrôlé par la ventilation avec pression expiratoire positive.

We report a case of traumatic chylothorax which occurred after a right subclavian vein catheterisation. Chyle output exceeded 4 L.day-1 despite a continuous drainage of the pleural space, cessation of oral intake and mechanical ventilation. It was cured by addition of PEP to ventilation. The various causes and therapeutic approaches are reviewed.

Congenital myasthenic syndrome due to rapsyn deficiency: three cases with arthrogryposis and bulbar symptoms.

We report the cases of 3 children with postsynaptic congenital myasthenic syndrome with acetylcholine receptor deficiency due to rapsyn deficiency. Symptoms began at the neonatal period with hypotonia, arthrogryposis, bulbar symptoms, and respiratory distress. Two of the 3 children needed tracheostomy and gastrostomy. Electromyograms showed a decremental response to repetitive stimulation. Muscle biopsies were normal or showed type I fiber preponderance. Genetic studies identified mutations in the rapsyn gene (RAPSN). The 3 patients were heterozygous for N88 K and a second mutation (either Y86X, 1083_1084 dupCT or IVS4-2 A > G). The patients responded favorably to anticholinesterase treatment, with a clear improvement of clinical symptoms, especially the bulbar symptoms of apneas and swallowing disturbances. This paper underlines the importance of anticholinesterase medication in patients with congenital myasthenic syndrome due to rapsyn deficiency.