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A family is described in which a hereditary peripheral neuropathy occurs, inherited as an autosomal dominant character. The syndrome is present at birth and does not show any significant progression thereafter. Three of the cases have suffered from arthrogryposis multiplex congenita. A secondary myopathy is also present. The condition appears to be intermediary between peroneal muscular atrophy and Friedreich's ataxia. Appearance at birth, presence of arthrogryposis multiplex congenita, and the non-progressive nature separate it sharply from the other heredofamilial ataxias and peripheral neuropathies.

This review deals with CNS troubles and anomalies (excluding mental defects and oligophrenia, as well as primary muscular degenerations), that account for approximately 25 percent of all cases of genetic counseling in our material.From a genetic-counseling perspective, CNS affections may be easily classed as follows: (1) congenital malformations; (2) monofactorial Mendelian affections; (3) diseases with a possibly hereditary disposition (e.g., arthrogryposis); (4) infant cerebral palsies; and (5) epilepsies.In our own material, CNS congenital malformations account for approximately 60 percent of all cases of neurologic genetic counseling, whereas Mendelian affections account for only 20 percent and epilepsies for 15 percent. They mainly include cases of hydrocephaly, anencephaly, spina bifida, and microcephaly, for which the recurrence risk is mostly empirical. Emphasis is laid on the present possibilities of prenatal detection of some of these malformations.

An infant affected by severe arthrogryposis multiplex congenita leading to death in infancy due to neurogenic atrophy is described. Six other sibs were similarly affected. An autosomal recessive mode of inheritance is suggested.

Two brothers (7 years of age and 8 months respectively) are reported. They both suffered from a combination of severe microcephaly, spastic tetraplegia, clonic epileptic fits, absent abdominal cutaneous reflexes and severe mental retardation. This syndrome shows an X-chromosomal mode of inheritance. Dermatoglyphic patterns were characteristic. There was no change in aminoacids in CSF and the birth weight was high (4000g, in contrast to the cases described by Warkany et al.).

1. The possibilities in the treatment of the elbow in arthrogryposis are discussed. 2. The role of tricepsplasty to gain movement, and of triceps transfer to obtain power are outlined and the results obtained in the surgical treatment of twenty-three elbows are analysed.

This study was designed to test in experimental animals the hypothesis (Renwick, 1972) that human spina bifida and anencephalus are causally related to maternal consumption of blighted potatoes. Gavaging of pregnant rats with blighted potatoes on days 5–11 or daily ip injections of solanine or glycoalkaloids (5–10 mg/kg) extracted from B5141-6 potatoes, given on days 5–12 or 7–17 of gestation, resuited in minor skeletal and renal tract abnormalities, but failed to produce neural-tube defects. Daily injections (days 5–12) of 20 and 40 mg/kg of the glycoalkaloid caused 100% fetal and maternal mortality, respectively. Daily ip injections of 5 mg/kg of solanine into New Zealand White rabbits on days 0–8 of gestation produced abortion in one-third of the treated animals, 23% resorptions, but no teratogenesis. Single yolk-sac injections of 5–20 mg/kg of solanine into 20–22 h incubated white Leghorn eggs produced 63–90% mortality within 72 h without significant teratogenesis. Diced B5141-6 potatoes containing an average of 260 mg of solanine per kg of tuber fed ad libitum to time-mated rhesus monkeys for a period of 25 days postcopulation produced no maternal toxicity; on the other hand single injections of 40 mg/kg of the glycoalkaloid extract and two injections of 20 mg/kg of solanine killed adults within 48 h of treatment. At autopsy nasal, oral, and periorbital hemorrhage was present; there was accumulation of serosanguinous pleural and peritoneal fluids and mild hepatic and splenic congestion. Examples of human toxicity and mortality from consuming potatoes with a high solanine content are reviewed.

Transfer of the triceps to the radius can restore active flexion to the paralyzed elbow when the preoperative indications for a Steindler flexorplasty cannot be met. Based on this series of fifteen patients, results are generally predictable in the paralytic and traumatic cases, but in arthrogrypotic patients, the results are less predictable, but still encouraging enough to justify further clinical use.

Two infants affected with the myopathic type of arthrogryposis multiplex congenita were studied. The muscle biopsies revealed similar light and electron microscopic changes in both patients, consisting of massive glycogen accumulation, disarray of myofilaments, and changes in mitochondria. All four parents of the two children are related to each other. Thus we propose that the myopathic type of arthrogryposis multiplex congenita is a specific genetic disease caused by a single gene and follows the autosomal recessive pattern of inheritance.

Medication with thalidomide (150.0 mg/kg) in pregnant New Zealand white rabbits resulted in a wide range of teratogenic changes in the kits. The most predominant effects were seen in the limbs (arthrogryposis, micromelia, absence of digits). When rhesus monkeys ( Macaca mulatta ) were fed thalidomide in the diet (150.0 mg/kg), interference with establishment of pregnancy occurred. No pregnancies were observed in the five medicated females while two unmedicated controls delivered normal young.

Summary (Table I) I. The factors concerned in maintainingnormal muscle tone have been described in detail as a background to the understanding of the possible sites of pathology which can lead to hypotonia. II. The causes of hypotonia in childrenunder 24 months of age have been discussed from the point of view of the presumed site of pathology. The classification which has evolved from this approach is as follows: A. Hypotonia due to diseases of thecentral nervous system: 1. Atonic diplegia 2. Congenital chorea and athetosis 3. Congenital cerebellar ataxia 4. Kernicterus 5. Mongolism 6. Tay-Sach's diseas B. Hypotonia due to diseases of thespinal cord: 1. Werdnig-Hoffman's disease (infantileprogressive muscular atrophy) 2. Myelopathic arthrogryposis multiplexcongenita 3. Congenital anterior poliomyelitis C. Hypotonia due to diseases of thespinal roots or peripheral nerves: 1. Acute and chronic polyneuropathy D. Hypotonia due to abnormalities of the myoneural junction: 1. Congenital myasthenia gravis 2. Neonatal (transient) myasthenia gravis E. Hypotonia due to diseases of themuscle: 1. Benign congenital hypotonia 2. Universal muscular hypoplasia 3. Congenital infantile muscular dystrophy with or without arthrogryposis multiplex congenita 4. Dystrophica myotonica 5. Central core disease 6. Rod body myopathy 7. Polymyositis 8. Glycogen storage disease III. The value of ancillary aids in thediagnosis of the etiology of hypotonia in infants has been discussed. These have included muscle biopsy, electromyography, measurement of the nerve conduction time, determination of serum enzyme concentrations, urinary creatine and creatinine excretion coefficients, and the assessment of the developmental level of the infant.

A patient with tuberous sclerosis exhibited the classic findings of arthrogryposis multiplex. It is evident that arthrogryposis may be the symptomatic result of a number of defects of the central nervous system.

1. The indications for talectomy in the treatment of equinovarus deformity in arthrogryposis multiplex congenita and spina bifida are discussed. 2. The technique of the operation is described, with variations which may be necessary in special circumstances. 3. The results of forty-one operations are analysed. 4. It is concluded that the operation has a useful place in the management of equinovarus deformity in arthrogryposis multiplex congenita and spina bifida, especially between the ages of one and five years.

Bei dem Patienten L. M. wurde neben einer Arthrogryposis multiplex congenita ein Kryptorchismus bei geistiger Retardierung festgestellt. Die Chromosomenalyse ergab die fur das Klinefelter-Syndrom charakteristische Chromosomenstorung (2n=47/XXY). Beim Barr-Test enthielten bei 248 analysierten Zellen der Mundschleimhaut 48 chromatinpositive Zellkerne. Die Untersuchung des Hautleistensystems zeigte im Bereich der Handflachen den fur die A. m. c. typischen longitudinalen Leistenverlauf. Auf allen Fingerbeeren sowie auf den Zehenbeeren 2–5 war eine volstandige Leistendysplasie vorhanden.

Two cases of arthrogryposis multiplex congenita are presented, and the literature relating to this rare condition is reviewed. It is concluded that arthrogryposis is a primary disease of the central nervous system, the musculoskeletal defects being secondary phenomena. Lesions of the anterior horn cells have been found most frequently, at times associated with pyramidal tract degeneration; isolated brain lesions have also been described. A genetic defect has not been ruled out, and some of the lesions with which this condition has been associated strongly suggest such an abnormality.

Arthrogryposis is a syndrome of contractures and multiple bone anomalies. The radiographic findings in 41 cases of this syndrome are discussed. A previously unreported carpal sign (increased carpal angle) which precedes carpal fusion is described.

Cholinesterase and β-naphthyl acetate esterase activities were determined in whole muscle homogenates of normal subjects and of patients with various muscular dystrophies and related myopathies. There was a moderate increase in muscle cholinesterase activity with respect to acetylthiocholine hydrolysis only in Duchenne muscular dystrophy. Cholinesterase and β-naphthyl acetate activities were essentially normal in the muscle from patients with myotonic dystrophy, other forms of muscular dystrophies, polymyositis and from one patient with myasthenia gravis. Muscle cholinesterase activity with respect to butyrylthiocholine and β-naphthyl acetate esterase activity were not markedly altered in Duchenne muscular dystrophy. Serum cholinesterase levels were normal in Duchenne muscular dystrophy and other dystrophies and in a few cases of polymyositis and spinal muscular atrophies.

Anomalies of the thumb which may be associated with congenital malformation syndromes include enlargement, duplication, and hypoplasia. The thumb may also be absent, have abnormal ossification centers, or be abnormal in position. The normative values of the ratio of the lengths of each bone to the others as well as to the second metacarpal are tabulated. These ratios are useful for objective evaluation of relative lengthening or shortening of the thumb bones. The radiographic appearances of the thumb in various syndromes are described and illustrated.

Verfasser schildern auszugsweise die Krankheitsgeschichte von 7 arthrogrypotischen Patienten, die Ergebnisse derer EMG-Untersuchungen und die Befunde der in 4 Fallen vorgenommenen histologischen Analyse. Arthrogryposis wird als ein Syndrome, das durch neurogene oder myogene Ursachen, gleicherweise aber auch durch beide zusammen entstehen kann, betrachtet. Diagnostische Probleme werden auch besprochen.

PREVIOUS interpretations of the pathologic processes underlying arthrogryposis multiplex congenita (AMC) have varied markedly. Recently, Smith et al1have concluded from electromyographic (EMG) observations in 14 patients and Drachman and Banker2,3have reported from necropsy studies that the underlying process was neurogenic. Adams et al4reported both neurogenic and myopathic cases confirmed by necropsy. There were decreased numbers of anterior horn cells in the spinal cord of cases considered to be neurogenic. Skeletal muscles showed small myofibers. In myopathic cases there were no spinal cord changes, but diffuse myopathic changes were present in muscle. Banker et al5reported the autopsy findings in a case of congenital muscular dystrophy, and Pearson and Fowler6described a necropsy of hereditary nonprogressive muscular dystrophy as causes of arthrogryposis. Bargeton et al7found changes indicating a collagen disease in their autopsied patient, and in ther opinon the collagen

Three further cases of the recently discovered “trisomy-brachygnathia syndrome” in cattle have been described. The syndrome consists of autosomal trisomy, brachygnathia inferior, and, in some cases, malformations such as arthrogryposis, hydrocephalus, cryptorchism, and heart anomalies. An indication of the possible genetical etiology of the syndrome is given by the teratograms of the sires.

The literature concerning the measurement of conduction velocity in human motor nerves and its clinical applications is reviewed. The chief value of the test to the clinician lies in the demonstration of a peripheral neuropathy and in its differentiation from myelopathy and myopathy. It is pointed out that this investigation is often particularly useful in infants and children as it is an objective and relatively painless test requiring little co-operation from the patient. Starting from approximately half the normal adult value at birth in full-term infants the motor nerve conduction velocity normally increases to the full adult level during the first 3 to 5 years of life. In premature infants it begins at a still lower level. This increase is of clinical interest and can be studied serially. There is also a particular developmental aspect in infants in relation to possible delays or disturbances of innervation or myelination. The results of measurements of conduction velocity, chiefly in the median nerves, are reported in 45 "normal" infants and children and in 100 others who had a variety of neurological disorders. The rate was normal in all but one of 33 children with miscellaneous cerebral disorders, including nonspecific mental retardation, Down's syndrome (mongolism), D1 trisomy, hydrocephalus, and organic convulsive disorders. There was a distinct reduction in metachromatic leucodystrophy (2 cases), infantile amaurotic idiocy (1 case), and recurrent and chronic polyneuropathy (3 cases). In 4 children with acute neuronitis there were no demonstrable gross changes in conduction velocity during the first 2 months, while the diminished voltage and increased temporal dispersion of the action potential were more helpful early diagnostic features. Normal results were obtained in benign congenital hypotonia (10 cases), phenylketonuria (3 cases), and ataxia-telangiectasia (1 case). Five children with Friedreich's ataxia were examined and 2 of these had marked clinical fluctuations in the extent of their weakness suggestive of peripheral neuropathy. One of the latter was seen during an acute exacerbation of his weakness when he had a distinctly reduced nerve conduction velocity, and prolonged terminal latency from wrist to thenar eminence. The other was tested during a phase of relative well-being and had a normal conduction velocity but even more prolonged terminal latency than the first. The remaining children had a slowly progressive illness; all of them had normal conduction velocity, but one had just significantly prolonged terminal conduction time. Somewhat slow conduction rates for the age appeared to be present in 1 of 6 infants with arthrogryposis multiplex congenita and in 4 of 14 with clubfoot below the age of 2 years, but the statistical significance of these deviations cannot yet be indicated. The results are discussed, with particular emphasis on developmental aspects and the involvement of the peripheral nervous system in "dysmyelination" and demyelination.

The pathology and radiographic examination of spontaneous carpal coalition in arthrogryposis suggests that loss of joint spaces is an acquired feature and does not stem from primary lack of joint space formation as has been previously suggested. The characteristic total carpal fusion in arthrogryposis is unique and may aid in differential diagnosis when present. Finally, the anatomical location is selective and no fusions have been described in the feet of subjects with this disorder. Emphasis in the future should be towards obtaining further joint specimens for pathologic study and making careful radiographic examinations to determine the evolution of die coalition and possible occurrence in other anatomic sites.

Sixteen cases with arthrogryposis multiplex congenita were examined clinically and electromyographically; three of them were re-examined later. Joint deformities were present in all extremities in 13 of the cases; in eight there was some degree of mental retardation. In two cases, there was clinical and electromyographic evidence of a myopathic disorder. In the majority, the appearances of the shoulder-neck region suggested a developmental defect. At the same time, selective weakness of muscles innervated by C5-C6 segments suggested a neuropathic disturbance. EMG revealed, in eight of 13 cases, clear evidence of denervation of muscles, but without any regenerative activity. The non-progressive nature of this disorder and capacity for improvement in muscle bulk and power suggest that denervation alone cannot explain the process. Re-examination of three patients after two to three years revealed persistence of the major deformities and muscle weakness noted earlier, with no appreciable deterioration.

Summary1. Resyl (o-methoxyphenylgly-cerol ether) has been found to block effectively the transmission of impulses through the internuncial units of spinal reflex arcs in cats in doses of 75 mg/kg. 2. On a mg/mg basis Myanesin is about 3 times more active than Resyl, however, on the basis of the ratio of activity to toxicity Resyl and Myanesin appeared to be equally effective.

Arthrogryposis multiplex congenita, or amyoplasia congenita, was probably first described by Otto in 1841 (1). Rocher (2) collected 31 cases of the disease from the literature in 1913, giving it the name of multiple congenital rigidities. Stern (3) introduced the term arthrogryposis multiplex congenita in 1923. In 1932, Sheldon (4) suggested the shorter designation, amyoplasia congenita. Further descriptions and case presentations followed, by Steindler (5), Hillman and Johnson (6), Badgley (7), and others. Clinical Features Arthrogryposis multiplex congenita is present at birth and is recognizable by the presence of flexion and∕or extension contractures of a few or many of the joints of the extremities. In many cases all four extremities are affected; in other instances a single limb is involved. Brandt (8) has stated that the infant looks like a wooden doll. The disease is generally symmetrical and is probably the result of incomplete development or failure of development of one or more muscle groups du...

Summary A case of arthrogryposis multiplex congenita in a girl, who died three days old, is described. Microscopy of the spinal cord revealed total loss of the motor cells of the anterior horn. The characteristics of this neurogenic disorder and its relation to myogenic a.m.c. and to Werdnig Hoffmann's disease are discussed.

Pathological findings are reported on 34 specimens from 16 cases of arthrogryposis multiplex congenita (AMC), including initial observations on paraffin sections from 28 muscles, and subsequent observations on six additional specimens from three of these cases studied both histologically and histochemically. Thirteen of the 34 specimens (from 11 cases) were histologically normal, probably on account of an unaffected muscle being sampled. The most constant pathological feature in the remaining specimens was a disorganization of the muscle fibres and fascicles by severe fibrosis; only three specimens (from two cases) did not show this. Very thin faintly striated muscle fibres embedded in this matrix were encountered in 10 specimens from nine cases. An attempt at grouping of these atrophic or ill-developed fibres was noticed in four specimens; but this may not be denervation atrophy. Two specimens (from two cases) showed `myopathic' features. Repeat biopsy after two to three years was carried out on two affected muscles each from three patients. Case 3 showed well preserved but uniformly small fibres. Case 4 showed extremely few and scattered small rounded fibres. Case 14 showed pronounced variation of fibre size in both, with both atrophic and hypertrophied fibres. Normal nerves and spindles were seen in all these six specimens irrespective of the state of the muscle, and excessive fibro-fatty tissue in cases 4 and 14. Histochemical examination for oxidative enzymes, ATPase, and phosphorylase in these six specimens revealed a normal checkerboard pattern and ratio of type I and type II fibres, in case 3 only. The muscles of case 4 showed a preponderance of type I fibres. One specimen from case 14, showed the same fibres reacting for both oxidative enzymes and phosphorylase, suggesting a lack of development of fibres. The intrafusal fibres were mainly of type I in all. Two possible pathogenetic mechanisms operating in early embryonic life, which may lead to the characteristic changes of AMC, are discussed: (1) a defect in the development of the muscle whereby the full recruitment of myoblasts from the mesenchyme of the limb-bud does not take place and muscles do not form adequately; (2) a lack of innervation of the muscles on account of arrested growth of anterior horn cells. The combined operation of both these mechanisms is also considered. Fibrous tissue replaces the muscle tissue that is lacking, and contractures and deformities ensue. The evidence gathered on our material, such as the very thin smooth muscle fibres, the large numbers of well-formed nerves and spindles especially in the repeat biopsies, and the above-mentioned histochemical feature, would appear to favour the hypothesis of ill-developed muscles in the production of AMC in the majority; in the rest denervation playing either a major or concurrent role.

Summary An attempt has been made to outline the principles generally followed in the treatment of talipes equinovarus in infancy at the Children's Hospital Medical Center. These methods have held up well over the years. Variations naturally occur from individual preferences. The correction of the equinovarus foot can best be accomplished by starting a detailed and thorough corrective program the day of birth. A large part of the correction should be accomplished within ten days to two weeks and prior to the use of casts. Overcorrection with casts, holding with bivalved casts, and a thoroughly supervised exercise program by the parents is essential. If treatment is delayed and correction cannot be attained in a reasonable time, or if the feet are unusually stiff as in arthrogryposis, surgery should not be unduly postponed, either in heel cord lengthening or medial ligamentous release. Postoperative care must be thorough and long. Otherwise recurrence is common. A child must wear out several pairs of shoes without deformity before supervision can be relaxed.