Congenital agenesis of the superficial posterior compartment calf muscles in a 13-month-old infant.

Muscle agenesis may induce cosmetic and functional deficits, particularly if the muscle is an axial limb or a large muscle. Limb muscle agenesis is a rare condition. Here, the authors report the case of a 13-mo-old girl with unilateral atrophic calf and gait abnormality. Magnetic resonance imaging confirmed agenesis of the posterior superficial compartment of the calf. The patient showed an out-toeing calcaneal gait and fibular length discrepancy secondarily during growth. Normal embryology and the differential diagnostic point of foot deformity as well as the clinical implications of calf agenesis are described.

Congenital absence of superficial posterior compartment calf muscles.

Although various congenital abnormalities have been described, congenital absence of calf musculature is extremely rare, with only one report on its complete absence. We are the first to describe a case of congenital absence of muscles of the superficial posterior compartment of the calf presenting in a toddler. The child presented with a history of a painless limp, however no significant difference was found in functional gait analysis. We suggest that such cases should be monitored and parents can be reassured that no immediate treatment is required.

Congenital lower brachial plexus palsy due to cervical ribs.

Congenital brachial plexus palsy (CBPP) usually occurs secondarily to intrapartum trauma, but this is not always the case. Cervical ribs have previously been reported to increase the risk of CBPP in association with birth trauma. We report the cases of two children (one female, one male) with congenital lower brachial plexus palsy in whom the presence of non-ossified cervical ribs was the only identified risk factor. In the female child magnetic resonance imaging (MRI) of the brain, spinal cord, and brachial plexus revealed no abnormality except for the presence of bilateral cervical ribs at the level of the seventh cervical (C7) vertebra. Chest radiography was normal, which suggested that the cervical ribs identified on the MRI were fibrous bands or cartilaginous ribs rather than ossified ribs. In the male child, MRI of the spine and brachial plexus was normal but he was noted to have bilateral cervical ribs at C7. These were not identifiable on chest radiography and, therefore, are likely to reflect fibrous bands or cartilaginous ribs.

An autosomal recessive syndrome of joint contractures, muscular atrophy, microcytic anemia, and panniculitis-associated lipodystrophy.

CONTEXT: Genetic lipodystrophies are rare disorders characterized by partial or complete loss of adipose tissue and predisposition to insulin resistance and its complications such as diabetes mellitus, hypertriglyceridemia, hepatic steatosis, acanthosis nigricans, and polycystic ovarian syndrome. OBJECTIVE: The objective of the study was to report a novel autosomal recessive lipodystrophy syndrome. RESULTS: We report the detailed phenotype of two males and one female patient, 26-34 yr old, belonging to two pedigrees with an autosomal recessive syndrome presenting with childhood-onset lipodystrophy, muscle atrophy, severe joint contractures, erythematous skin lesions, and microcytic anemia. Other variable clinical features include hypergammaglobulinemia, hepatosplenomegaly, generalized seizures, and basal ganglia calcification. None of the patients had diabetes mellitus or acanthosis nigricans. Two had mild hypertriglyceridemia and all had low levels of high-density lipoprotein cholesterol. Skin biopsy of an erythematous nodular skin lesion from one of the patients revealed evidence of panniculitis. The lipodystrophy initially affected the upper body but later became generalized involving abdomen and lower extremities as well. CONCLUSIONS: We conclude that these patients represent a novel autoinflammatory syndrome resulting in joint contractures, muscle atrophy, microcytic anemia, and panniculitis-induced lipodystrophy. The molecular genetic basis of this disorder remains to be elucidated.

Evidence of an asymmetrical endophenotype in congenital fibrosis of extraocular muscles type 3 resulting from TUBB3 mutations.

PURPOSE: Orbital magnetic resonance imaging (MRI) was used to investigate the structural basis of motility abnormalities in congenital fibrosis of the extraocular muscles type 3 (CFEOM3), a disorder resulting from missense mutations in TUBB3, which encodes neuron-specific beta-tubulin isotype III. METHODS: Ophthalmic examinations in 13 volunteers from four CFEOM3 pedigrees and normal control subjects, were correlated with TUBB3 mutation and MRI findings that demonstrated extraocular muscle (EOM) size, location, contractility, and innervation. RESULTS: Volunteers included clinically affected and clinically unaffected carriers of R262C and D417N TUBB3 amino acid substitutions and one unaffected, mutation-negative family member. Subjects with CFEOM3 frequently had asymmetrical blepharoptosis, limited vertical duction, variable ophthalmoplegia, exotropia, and paradoxical abduction in infraduction. MRI demonstrated variable, asymmetrical levator palpebrae superioris and superior rectus EOM atrophy that correlated with blepharoptosis, deficient supraduction, and small orbital motor nerves. Additional EOMs exhibited variable hypoplasia that correlated with duction deficit, but the superior oblique muscle was spared. Ophthalmoplegia occurred only when the subarachnoid width of CN3 was <1.9 mm. A-pattern exotropia was frequent, correlating with apparent lateral rectus (LR) muscle misinnervation by CN3. Optic nerve (ON) cross sections were subnormal, but rectus pulley locations were normal. CONCLUSIONS: CFEOM3 caused by TUBB3 R262C and D417N amino acid substitutions features abnormalities of EOM innervation and function that correlate with subarachnoid CN3 hypoplasia, occasional abducens nerve hypoplasia, and subclinical ON hypoplasia that can resemble CFEOM1. Clinical and MRI findings in CFEOM3 are more variable than those in CFEOM1 and are often asymmetrical. Apparent LR innervation by the inferior rectus motor nerve is an overlapping feature of Duane retraction syndrome and CFEOM1. These findings suggest that CFEOM3 is an asymmetrical, variably penetrant, congenital cranial dysinnervation disorder leading to secondary EOM atrophy.

The IGF-I splice variant MGF increases progenitor cells in ALS, dystrophic, and normal muscle.

The effects of muscle splice variants of insulin-like growth factor I (IGF-I) on proliferation and differentiation were studied in human primary muscle cell cultures from healthy subjects as well as from muscular dystrophy and ALS patients. Although the initial numbers of mononucleated progenitor cells expressing desmin were lower in diseased muscle, the E domain peptide of IGF-IEc (MGF) significantly increased the numbers of progenitor cells in healthy and diseased muscle. IGF-I significantly enhances myogenic differentiation whereas MGF E peptide blocks this pathway, resulting in an increased progenitor (stem) cell pool and thus potentially facilitating repair and maintenance of this postmitotic tissue.

[Congenital hemiplegia. A disease with manifold problems]. / Kongenitale Hemiplegie. Eine Krankheit mit vielen Problemen.

Congenital hemiplegia, defined as unilateral motor disability, is the hemiplegic type of cerebral palsy. The prevalence of congenital hemiplegia is estimated to be about 0.41-0.79/1000 live births. We examined 223 children (122 boys and 101 girls) suffering from congenital hemiplegia at the age of 3 months to 12 years. Mild hemiplegia was found in 31%, a moderate form in 48%, and a severe form in 21%. The upper limb was affected in more than half of the patients, only the lower extremity in one third, and both upper and lower limbs in 20%. Electroencephalographic abnormalities were found in 75.8% of the patients. The most frequent type of epilepsy was complex partial seizures (33%). Severity of the motor handicap, grade of EEG abnormalities, and the prevalence of epilepsy showed a significant correlation. The magnitude of the lesions in neuroimaging directly correlated with these three clinical variables, particularly in children with cortical and subcortical defects (84.2%). Strabismus was the most common visual impairment (17%), while hearing impairment was found in 8% of the patients. Of them, 38.3% showed no cognitive deficits, while those with severe congenital hemiplegia were found to have a lower intelligence quotient.

Porcine congenital splayleg is characterised by muscle fibre atrophy associated with relative rise in MAFbx and fall in P311 expression.

BACKGROUND: Porcine congenital splayleg (PCS) is the most important congenital condition of piglets, associated with lameness and immobility, of unknown aetiology and pathogenesis, hence the need to better understand the condition by defining, in the first instance, its histopathology and molecular pathology. RESULTS: Semitendinosus, longissimus dorsi, and gastrocnemius muscles were removed from 4 sets of 2-day-old splayleg piglets, each with a corresponding normal litter mate. Based on immunohistochemistry and histological image analysis, PCS piglets showed significantly smaller fibre size without any accompanying sign of inflammation. Although there was no dramatic change in fibre type composition in affected muscles, several structural myosin heavy chain genes were significantly down-regulated. MAFbx, a major atrophy marker, was highly up-regulated in nearly all PCS muscles, in comparison with controls from normal litter mates. In contrast, P311, a novel 8 kDa protein, was relatively down-regulated in all the PCS muscles. To investigate a functional role of P311 in skeletal muscle, its full-length cDNA was over-expressed in murine C2C12 muscle cells, which resulted in enhanced cell proliferation with reduced myotube formation. Hence, reduced P311 expression in PCS piglets might contribute to atrophy through reduced muscle cell proliferation. P311, predictably, was down-regulated by the over-expression of calcineurin, a key signalling factor of muscle differentiation. CONCLUSION: We demonstrated that PCS is a condition characterised by extensive fibre atrophy and raised fibre density, and propose that the combined differential expression of MAFbx and P311 is of potential in the diagnosis of subclinical PCS.

Expression, localization and functional divergence of alphaB-crystallin and heat shock protein 27 in core myopathies and neurogenic atrophy.

AlphaB-crystallin (alphaBC) and heat shock protein 27 (hsp 27) are members of the family of small heat shock proteins (shsps), which exert a role as molecular chaperones by binding unfolded or denatured proteins, thereby suppressing irreversible protein aggregation and consecutive cell damage. The essential role of shsps in human neuromuscular disorders is highlighted by the observation that a mutation of the human alphaBC gene causes an autosomal dominant "myofibrillar myopathy" characterized by alphaBC and desmin accumulation. Furthermore, an aberrant immunostaining of alphaBC was recently reported in sporadic inclusion body myositis. In the present study we analyzed the expression and localization of alphaB-crystallin and hsp 27 in various congenital myopathies by means of indirect immunofluorescence, immunogold electron microscopy and Western blotting. We demonstrate an increased immunoreactivity of alphaBC and hsp 27 in central and minicore lesions as well as in target fibers, which renders both shsps as reliable, but nonspecific, markers for core and target structures. In contrast, Western blotting demonstrated a normal expression level of alphaBC and hsp 27, which indicates that the increased immunostaining is not the result of an enhanced protein expression. Furthermore, thiocyanate-induced degradation of actin filaments led to a dramatic decrease of hsp 27 immunostaining in core and target lesions, whereas the increased alphaBC and desmin immunostaining was found to be even more enhanced. The latter findings imply a functional diversity of both shsps with a preferential association of hsp 27 with the actin microfilament system and alphaBC with the intermyofibrillar desmin cytoskeleton in human skeletal muscle.

Congenital contractural arachnodactyly with neurogenic muscular atrophy: case report.

We report the case of a 3-(1/2)-year-old girl with hypotonia, multiple joint contractures, hip luxation, arachnodactyly, adducted thumbs, dolichostenomelia, and abnormal external ears suggesting the diagnosis of congenital contractural arachnodactyly (CCA). The serum muscle enzymes were normal and the needle electromyography showed active and chronic denervation. The muscle biopsy demonstrated active and chronic denervation compatible with spinal muscular atrophy. Analysis of exons 7 and 8 of survival motor neuron gene through polymerase chain reaction did not show deletions. Neurogenic muscular atrophy is a new abnormality associated with CCA, suggesting that CCA is clinically heterogeneous.

Congenital contractural arachnodactyly with neurogenic muscular atrophy: case report

We report the case of a 3-1/2-year-old girl with hypotonia, multiple joint contractures, hip luxation, arachnodactyly, adducted thumbs, dolichostenomelia, and abnormal external ears suggesting the diagnosis of congenital contractural arachnodactyly (CCA). The serum muscle enzimes were normal and the needle electromyography showed active and chronic denervation. The muscle biopsy demonstrated active and chronic denervation compatible with spinal muscular atrophy. Analysis of exons 7 and 8 of survival motor neuron gene through polymerase chain reaction did not show deletions. Neurogenic muscular atrophy is a new abnormality associated with CCA, suggesting that CCA is clinically heterogeneous

Sleep-disordered breathing in a patient with congenital myopathy.

A case of adult onset myopathy who showed a peculiar sleep-related respiratory disorder (SRRD) is reported. She recovered from respiratory failure after tracheostomy and/or with the aid of the respirator used only during the night. Sleep study without the use of respirator revealed that her sleep was highly fragmented by frequent arousal responses due to inspiratory effort but not by apnea or hypopnea. To our knowledge this type of SRRD has not been described.

Neonatal perifascicular myopathy.

Perifascicular atrophy of muscle fibers is generally considered to be a specific feature of autoimmune myopathies, dermatomyositis in particular. We describe a neonate presenting with hypotonia and weakness. A biopsy revealed atrophic and regenerating muscle fibers in a perifascicular distribution, and abnormal alkaline phosphatase activity in neighboring perimysial connective tissue. The weakness was nonprogressive and improved on follow-up even though no long-term treatment was administered. We conclude that the presence of perifascicular myopathic changes and muscle fiber atrophy in infants presenting with hypotonia and weakness is neither diagnostic of progressive dermatomyositis, nor a necessary indication for immunosuppressive therapy.

Association of Krabbe leukodystrophy and congenital fiber type disproportion.

Hypotonia and weakness developed in a 12-month-old boy whose psychomotor development had previously been normal. The muscle biopsy demonstrated a disparity in the mean diameters of type 1 and type 2 fibers and satisfied major histologic criteria for diagnosis of congenital fiber type disproportion (CFTD). However, deterioration of motor and mental function, which developed subsequently, strongly suggested progressive encephalopathy. Examination of leukocyte cerebral enzymes at 15 months of age revealed a complete lack of galactosylceramide-beta-galactosidase. Selective type 1 fiber atrophy with type 1 fiber predominance has been observed in various conditions, including Krabbe disease. We report an additional case of Krabbe leukodystrophy associated with CFTD. The finding on the molecular level will resolve the dilemma of whether CFTD is a congenital myopathy or whether these patterns of disproportion may result from a number of different processes that interfere with the maturation of the developing motor unit.

Central-type eight-toed polydactyly associated with ipsilateral complex renogluteal agenesis: a case report with 8 years' follow-up.

At birth, a baby girl was found to have central-type eight-toed polydactyly of the left foot associated with ipsilateral nonvisualization of the kidney and atrophy of the gluteal maximum muscle. X-ray examination showed eight completely developed metatarsal and digit bones, and a chromosome study showed a normal 46, XX karyotype. She received ray amputation of the extra toes when she was 1 year old. Follow-up examination at age 9 showed unchanged renogluteal anomalies and a slightly smaller left foot. In addition, a bony defect over the posterior iliac spine and a wide femoral neck-shaft angle were found on the radiograph. Her left leg was found to be 1 cm shorter than the right, but there was no evidence of valgus or varus. Presently she can walk and run quite well, and there is no callus formation over her sole. The timing and options for excision of the supernumerary digits are discussed and this rare disease reviewed.

Miopatía centro nuclear tardía: forma autosómica dominante / Later centronuclear myopathy: autosomal dominant form

We report a family with three generation affected by an autosomal dominant centronuclear palsy. This gene is characterized by ptosis that begins in childhood and a slowly progressive weakness that starts in the second decade of life, involving face, neck and limbs. In this stage, muscle pan associated to exercise or cold muscle sparms may apprear. The gene is expressed with differing intensity in each individual. Myopathic electro myographic alterations are only found in fuctionally impaired subjects. Muscle biopsy shows type I fiber atrophy and central nuclei in a high percentage of fibers, specially in type I fibers

Cytoplasmic body myopathy with hypertrophic cardiomyopathy.

A patient with cytoplasmic body myopathy presented muscle hypotonia from birth and developed progressive muscular atrophy and weakness, scoliosis, contracture of joints and cardiorespiratory failure. At the age of 17, he died of heart failure. Post mortem examination revealed severe hypertrophy of cardiac walls and generalized muscular atrophy. Microscopic examination showed many cytoplasmic bodies in skeletal muscle fibers and myofiber disarray in myocardium. No cases of cytoplasmic body myopathy with hypertrophic cardiomyopathy have been reported previously. It is suggested that the Z-line component is related to the formation of the cytoplasmic body in skeletal muscle and disarray in the cardiac muscle.

Late presentation of congenital muscular torticollis: use of MR imaging and CT scan in diagnosis.

A 17-year old boy presented with a 10-year history of progressive head tilt to the right. Bilateral posterolateral cervical pain was mild and he was fully functional. The right sternocleidomastoid (SCM) muscle was prominent without rotation of the head to the left. The SCM had a cord-like consistency on palpation. Magnetic resonance (MR) and computed tomography (CT) scan imaging of the neck musculature suggested fibrous tissue within the substance of the muscle. This was histopathologically confirmed when the right SCM was surgically explored and resected. Congenital muscular torticollis is usually seen in newborns, infants, and children but may also present in adolescence and young adulthood. It should be included in the differential diagnosis of cervical dystonia as one of the nondystonic causes of abnormal head posture. Combined use of MR and CT scan of neck muscles may be of help in the diagnosis.