Dcvelop. Mcti. Child Nciirol. 1966, 8, 330-335

Neil Gordon

Benign Congenital H ypotonia A Syndrome or a Diseuse

THE differential diagnosis of the floppy infant embraces many aspects of medicine (Walton 1960). If hypotonia persists as the child grows older and obvious central causes, such as mental deficiency, can be excluded, the possibility of a lower motor neurone or niuscular disorder will be i n - creasingly considered. At the beginning of the century the diagnosis might well have been amyotonia congenita (Collier and Wilson 1908). This term has fallen into disrepute, mainly because such follow-up studies as those of Brandt (1950) have shown that many patients diagnosed as having this condition are i n reality cases of infantilespinal muscular atrophy( Werdnig- Hoffman's disease).

The alternative diagnosis that can pos- sibly be made is 'benign congenital hypotonia'. This term, as defined by Walton (l96O), includes those children not suffer- ing from infantile spinal muscular atrophy, or from any symptomatic form of hypo- tonia. There is no doubt that the clinical picture of Werdnig-Hoffman's disease has a much wider range of severity than was originally described (Dubowitz 1964). Children with this condition can survive into adult life, although remaining severely disabled. The symptomatic group contains many disorders varying from polyneuritis, polymyositis and muscular dystrophy to

brain injury, and to conditions such as coeliac disease and rickets. When no cause can be found for the hypotonia. the diagnosis of benign congenital hypotonia will probably be considered. I t will still tend to be a diagnosis of exclusion, and i t seems doubtful if the condition can be regarded i is a clinical entity. I n fact. like many other terms in medicine. there may be a danger in implying that ;I di;rpnosis has been made.

Benign congenital hypotonia may n o t embrace so many conditions a \ amyotonia congenita, but the possibility th;i t i t still contains a number o f diti'erent diseases should be Considered. Wallon (1900) lists the characteristics of benign congcni- tal hypotonia as impaired spontaneous mobility of the limbs, delay in physical development and a generalised muscular hypotonia; aftera variable period. improve- ment is the rule, and a proportion o f the cases recover completely. This subdivision into two groups of children sonic who can in later life be passed as norinal, and others w h o remain disabled even it ' the condition is stationary- -raises sus- picions of differing causations. Sometimes the electromyogram may give abnormal patterns, but often i t seems to be normal, as d o biopsy specimens from the muscle. Admittedly in conditions such as central

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core disease special techniques may be needed to demonstrate a significant lesion (Shy and Magee 1956). but conditions of this type appear to leave the patient severely disabled even if they do not progress.

Walton (1957) followed up 17 children, all of whom had been limp 'floppy' babies, who showed a marked delay in reaching the motor milestorles indicative of norm- ally increasing muscular activity. None of them were considered to be suffering from spinal muscular atrophy or symptomatic hypotonia. Of the 17 children, 8 recovered completely; the rest improved in early childhood but at follow-up examin a t ' ion showed evidence of a persisting but non- progressive muscular disorder. Walton stresses that the initial histories of the children who recover and of those who do not are almost identical, and concludes that they can all be included in the syndrome of benign congenital hypotonia. The natural history of the condition may support the identification of a syndrome, but this is not to suppose that it has a uniform causation. The contrast between the children who recover completely and those who remain disabled is bound to excite comment. Among any series of patients who initially fulfil the criteria of benign congenital hypotonia, there will probably always be some i n whom progress is good and the condition truly benign, and others whose progress is less satisfactory.

Clinical Features In the first month or two of life the child

with severe hypotonia is most likely to be suffering from infantile spinal muscular atrophy, and at six months from cerebral palsy. When the child is a few years old at the time of assessment, the diagnosis becomes more complicated. It may still be spinal muscular atrophy and rarely a type of muscular dystrophy. More commonly, the child will be suffering from mental

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retardation or from the hypotonic forms of cerebral palsy (Lesny 1960). When these and other causes of hypotonia, particularly the symptomatic group, have been excluded there will be a few children who can be classified a s examples of benign congenital hypotonia. Paine (1963) has emphasised that this is a diagnosis of exclusion. In his series, there were 21 children in this cate- gory out of a total of 133 with infantile hypotonia. He includes those with a family history of such features as double- jointedness, although congenital laxity of the ligaments with hypotonia (Catzel 1955) may be a separate condition in which muscle power is said to be normal with no reduction in muscle size.

In the early stages it will not be possible to differentiate between the child w h o is going to remain disabled and the one who will recover, although the degree of dis- ability may give some guidance.

Case-Records Case 1 A girl, born in March, 1960. The birth was normal with a birth weight of 9 Ib. 8 oz. At the age of ten months the baby was hypotonic, with no idea of crawling. The tendon jerks could not be elicited. Six months later she could sit up and was taking more notice of her surroundings. The legs were more hypotonic than the arms. A diagnosis of benign congenital hypotonia was made and further investiga- tions were carried out. The EMG was normal and a muscle biopsy showed no significant findings. X-ray examination of the spine and the CSF were normal. The serum aldolase and transaminases were not raised. When the patient was two years old she could sit up for short periods unaided, her arm movements were stronger, but her leg movements were still very weak. Im- provement continued over the next three years, but the child remained severely dis- abled. Although arm movements were

DEVELOPMENTAL MEDICINE AND CHILD NEUROLOGY. 1966, 8

nearly normal, the hands were still awk- ward to use; for instance, the child had difficulty in feeding herself. She could not stand up unaided.

Some of these severely affected children may be suffering from the effects of brain damage, and it is ditficult to exclude such possibilities as infantile polyneuritis and non-progressive forms of myopathy. The difficulties of diagnosis are well recognised and also the limited repertoire of symptoms that the motor system can produce when its function is interfered with.

Those ‘floppy’ infants with benign con- genital hypotonia who recover completely as they grow older show no characteristic features.

C(1SC 2 A boy, born in April, 1962. The pregnancy was normal, except for some bleeding just before birth. Birth was by breech delivery, the weight being 8+ Ib. Breathing was delayed for a few minutes, but no oxygen was given. The child sat at seven months, crawled at a year, and stood with support at 15 months but remained unusually floppy. At two years old he could stand on his own and a few months later began to walk, although unsteadily. Speech de- veloped normally.

On examination at the age of two, muscle tone in the legs was reduced, although the reflexes were abnormally brisk. The plantar responses were flexor. The gait was ataxic. The CSF was normal. The serum aldolase and creatine kinase were within normal limits. A muscle biopsy was normal. Six months later walking had improved, although slight hypotonia re- mained. The IQ was 108 on the Terman- Merrill test.

Case 3 A girl born in January, 1962, by forceps

delivery at full term, because of breech

presentation and foetal distress. Her birth weight was 6 Ib. She was not i l l in the neonatal period but sufrered from de- hydration at the age of two months. She sat alone at about seven months. hut remained a floppy baby who made no attempt to crawl. Examination conlirmed the hypotonia and the tendon reflexes were sluggish. Just before the p:!tient was two years old, she began to pul l hersell’ onto her feet and started to walk soon after- wards. When assessed a year later. she was walking steadily and development was considered to be normal.

Case 4 A boy, born in January. 1962. The

pregnancy was normal, but the birth was 26 days post-mature. I t had to he surgically induced and the placenta removed manu- ally. He smiled at the normal time, hut motor development was rctardcd. The limbs remained hypotonic and walking with support started at the age 01’ twenty months. A t this time the hypotonia was still evident, especially in the Icgs. and the child crawled around on his buttocks. Speech consisted of occasional words. Five months later he could walk on his own but still tended to fall a great deal. The hypo- tonia was much less evident. When just over three years old, the boy’s walking was normal and neurological examination showed no abnormalities.

Discussion The main reason for suggesting that the

children who remain disabled and those who recover completely are examples of the same clinical syndrome, wi th the implication of a uniform causation, is the similarity of the symptoms or signs in the early stages. There is no definite proof that the former group is always due to a single cause, although the evidence from such tests as EMG and muscle biopsy is in favour of a disease of muscle being responsible in

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most cases (Walton 1957). The early history of the children who ultimately recover may be exactly similar, but the different course of the condition would seem to be an equally powerful argument in favour of separating the two groups. The fact that some cases recover com- pletely suggests either that the lesion or disease is not present in them or that i t affects a part of the motor system in which complete compensation may occur. If the disorder is one of delayed development, this might be within the muscle itself. Even when the muscle biopsy examined by standard techniques shows nothing of significance, changes suggestive of an immature muscle have been demonstrated by special techniques. Coers and Pelc (1964) studied muscle from a single hypo- tonic patient, stained intravitally with methylene blue. The terminal fibres were ramified and the end-plates showed a simple dilatation, instead of the expected terminal arborizations of the nerve fibres and complex end-plates.

If the lack of tone is a developmental disorder, the disturbance of function is more likely t o lie within the central nervous system. The development of the normal child is a series of changing pos- tures, the flexor pattern predominating to begin with and then an increasing extension of the limbs and trunk becoming apparent. These changes and the increasing activity of the child must be due to the growth of the brain and the concomitant control of primitive reflex patterns. Milani (1964) suggests that to acquire the progressive refinement of selective motor behaviour, the massive gross functional units of primitive reflex patterns have to be broken down into small units available for the reconstruction of other new patterns. For this to proceed smoothly, all parts of the nervous system will have to commence functioning at their allotted time. If the development of one part is delayed, the

progression of changing postures will be distorted.

Is it possible that some of the children with benign congenital hypotonia who recover with increasing age are in fact suf- fering from the effects of delayed develop- ment of the connections of the gamma motor system? A lesion of the cerebellum may withdraw facilitating effects on the gamma system so that i t becomes almost inactive and hypotonia results (Rushworth 1962). If there was an initial failure in the integration of this system, the clinical picture might well be dominated by lack of tone and diminished reflexes. There are some developmental disorders in child- hood dependent on the delayed function of one particular part of the central nervous system-for instance, the child who is late in learning to talk or read. Most of these children recover completely, integration ultimately occurring by processes of com- pensation for any cerebral deficiencies. There seems no reason, therefore, why deyects in motor function resulting in hypo- tonia should not do likewise.

More stress might therefore be given to the possibility of defects in central mechanisms being the cause of hypotonia in infancy. Benign congenital hypotonia must remain a clinical syndrome until the causative factors are discovered, and, at this stage, it would seem better to emphasise that the syndrome may be due to a number of causes than to raise it to the rank of a disease by suggesting that all children pre- senting with this condition belong to a single entity. Paine (1963) considers that there are probably three groups: patients with family histories of double-jointedness, hypotonia or delay in learning to walk without neurological abnormalities; similar patients without positive family histories, some of whom may remain mentally retarded or 'clumsy' as they grow older; and patients with overt or borderline neurological defects.

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Ancillary investigations are often un- especially in the milder cases, a reason- helpful, so that the diagnosis of these ably optimistic attitude seems justified children is likely to depend on a by the knowledge that some of these period of observation. It may not be children do make a satisfactory re- possible to give an exact prognosis, but, covery.

SUMMARY Children suffering from benign congenital hypotonia can be divided into those who

remain disabled and those who recover. It would seem unlikely that this condition, although a clinical entity, has a single causation. Especially in the group with a favourable outcome, the hypotonia may well be due to a disorder of function in the central nervous system and not to the effect of a muscle disease. In some cases the condition may be an example of a developmental disorder of infancy, and further study on these lines may be rewarding.

RESUMC Hypotonie congknirale bknigne

Les enfants souffrant d’hypotonie congtnitale benigne se rangent en deux catkgories: ceux qui restent infirmes et se qui se ritablissent. II semblerait improbable que cet etat, bien qu’etant une entite clinique, ait une cause unique. En particulier chez le groupe a pronostic favorable, I’hypotonie peut bien Ctre dce A un disordre de fonction dans le systeme nerveux central lui-mCme et non A l’effet d’une maladie musculaire. Dans certains cas cet t tat peut Ctre un exemple d’un dtsordre du dtveloppement de la petite enfance; d’autres recherches dans cette voie seraient sans doute fructueuses.

ZUSAM MENFASSUNG Angeborene, gutarlige Hypotonie

Kinder die unter angeborener, gutartiger Hypotonie leiden, konnen in solche die korperbehinder bleiben und solche die gesunden, aufgeteilt werden. Es scheint unwahr- scheinlich zu sein, dass diesem Zustand, der obwohl er eine klinische Einheit darstellt, eine einzelne Ursache zugrunde liegt. Besonders bei der Gruppe mit gunstiger Prognosis, kann Hypotonie sehr wohl von einer FunktionsstGrung im Nervensystem herruhren und nicht von einer Muskelkrankheit. In bestimmten Fallen kann dieser Zustand Beispiel einer Entwicklungsstorung im Kleinkindalter sein und weitere Studien auf dieser Linie konnen sich als lohnend erweisen.

RESUMEN Hipotonia congknita benigna

Es posible dividir 10s niiios afectos de la hipotonia conginita benigna en dos grupo- 10s que quedan incapacitados y 10s que se reponen. No parece probable que este estado, aunque es una sola entidad clinica, tenga un solo origen. Sobre todo en el grupo cuyo pronostico es favorable, la hipotonia puede resultar de un trastorno de funcion dentro del sistema nervioso central, y no del efecto de una afeccion muscular. En ciertos caws el estado puede ser un ejemplo de un desorden de desarrollo infantil, y tal vez vale la pena de estudiar mis este aspecto.

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