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Congenital hypotonia with favorable outcome
Congenital Hypotonia With Favorable Outcome Pasquale Carboni, MD*, Francesco Pisani, MD†, Anna Crescenzi, MD‡, and Ciro Villani, MD§ Congenital hypotonia with favorable outcome is characterized by an early neonatal onset and a benign clinical course. The old term, proposed by Walton, was benign congenital hypotonia, denoting the presence of muscle weakness and hypotonia, with the exception of Werdnig-Hoffmann disease. It has been clear that this term includes congenital myopathies with definite changes in the muscle fiber. However, many cases remain unclarified. The term congenital hypotonia with favorable outcome includes only these last cases. A long-term follow-up study of children with congenital hypotonia with favorable outcome is presented, and a hypothetical mechanism underlying muscle shortening is discussed. The study was carried out at the Department of Child Neuropsychiatric Sciences, University “La Sapienza” of Rome, during the period 1985-2000, and included 41 patients with congenital hypotonia. Our study confirms the good prognosis of congenital hypotonia with favorable outcome and suggests a correlation with joint hyperlaxity, which is observed in many parents of our children, as if the latter developed from the former. On the basis of experimental changes occurring in the muscles, we believe that in our cohort the main cause of shortening is caused by an increase in joint mobility, which keeps muscles shortened in both the passive and active states for a long time. If this view is confirmed by other studies, we suggest continuous muscle exercise as a preventive treatment. © 2002 by Elsevier Science Inc. All rights reserved. Carboni P, Pisani F, Crescenzi A, Villani C. Congenital hypotonia with favorable outcome. Pediatr Neurol 2002; 26:383-386.
From the *Department of Child Neuropsychiatric Science; University “La Sapienza”; Rome; †Child Neuropsychiatric Unit; University of Parma; Parma; ‡Pathology Service; “Regina Apostolorum Hospital”; Albano Laziale; Rome; and §Department of Orthopaedy; University “La Sapienza”; Rome, Italy.
© 2002 by Elsevier Science Inc. All rights reserved. PII S0887-8994(02)00379-X ● 0887-8994/02/$—see front matter
Introduction Infantile hypotonia is the clinical phenotype of several disorders involving different system, such as brain, muscle [1,2], and connective tissue [3], or metabolic pathways. Walton [4] first used the term benign congenital hypotonia to describe a clinical condition of neonatal hypotonia, excluding Werdnig-Hoffmann disease, with a good prognosis. However, with the development of myology, it has been proved that benign congenital hypotonia included many myopathies with structural or biochemical changes in the muscle fiber or in certain contractile proteins of skeletal muscle. However, many benign congenital hypotonia cases remain unclarified, even with detailed examination of the muscle. As a consequence, we prefer to avoid the confusing old nomenclature of benign congenital hypotonia, and instead prefer the more restrictive term of congenital hypotonia with favorable outcome. Nevertheless, irrespective of the cause, congenital hypotonia with favorable outcome has value as a descriptive term for patients fulfilling the criteria suggested by Walton for benign congenital hypotonia [5-7]: (1) early hypotonia, usually since birth; (2) active movements of the limbs and normal tendon reflexes; (3) normal or mild motor retardation that improves later on; (4) muscle enzymes at normal levels, normal results of electromyographic examination and nerve conduction studies (the last was added by us), and essentially normal muscle biopsy findings. Although congenital hypotonia with favorable outcome is most likely a syndrome with more than one etiology and mode of inheritance [5], the clinical presentation of these children is very similar. Congenital hypotonia with favorable outcome is a common problem in the pediatric practice, but its longterm clinical evolution and prognosis are not clearly defined in the literature. Furthermore, we were surprised to see the association of congenital hypotonia with favor-
Communications should be addressed to: Dr. Pisani; Servizio di Neuropsichiatria Infantile; Via Gramsci, 14; 43100 Parma, Italy. Received January 3, 2001; accepted December 18, 2001.
Carboni et al: Congenital Hypotonia 383
able outcome and muscle contracture in few children and joint hyperlaxity in some of their parents. We present a long-term follow-up study of congenital hypotonia with favorable outcome, which determines the relation between congenital hypotonia with favorable outcome and joint hyperlaxity, and discuss the probable mechanism underlying muscle contracture. Patients and Methods A longitudinal study of congenital hypotonia with favorable outcomeaffected children and their parents was conducted at the Department of Child Neuropsychiatric Sciences of the University “La Sapienza,” Rome, Italy, from 1985 through 2000. We studied the correlation between congenital hypotonia with favorable outcome and joint hyperlaxity. On the basis of Walton’s [4] parameters for congenital hypotonia with favorable outcome, 41 patients of 39 kindreds were selected, 25 of which were males and 16 were females (9 months to 12 years of age; mean, 6.7 years when needle muscle biopsy was performed). We used the following exclusion criteria: (1) children with delayed cognitive development or abnormal thyroid function; (2) children with a history of hypoxicischemic insult; (3) children without a full investigation for muscle diseases (muscle serum enzyme activities, electromyography, motor and sensory nerve conduction studies, muscle biopsy with histologic, histochemical, and electron-microscopic studies); and (4) children demonstrating abnormalities in the tests listed in item 3. In most cases, pediatricians sent the youngest patients to a neurologist for assessment of hypotonia and motor delay, whereas orthopedic specialists sent the older patients to a neurologist for assessment of joint hyperlaxity. At neurologic investigation in all patients in whom hypotonia was observed, needle muscle biopsy was performed [8]. Each specimen was cut into two samples. The first sample was snap-frozen, and cryostatic sections were submitted for morphologic and histoenzymatic studies (ATPase, NADH, SDH, and acid phosphatase), and the second sample was fixed in buffered gluteraldehyde solution for electron microscopy.
Results The laboratory tests and needle muscle biopsy results of the vastus lateralis were normal. Long-term follow-up demonstrated very good improvement on gross motor performances (e.g., the patients observed at 15 years of age walked and ran without problems). Patients with a familial etiology did not differ in clinical evolution from patients with a nonfamilial etiology. We report the clinical features of our patients in different postures (sitting, standing, and walking) and their clinical evolution. Sitting All patients easily assumed the “w” position of the lower limbs, with their bottom on their heels. In such a position the feet maintain an excessive clubfoot posture.
load, and enhancement of plantar arch (pes cavus) when the feet were not weight bearing. Gait The foot out load is maintained basically in passive equilibrium and after being slapped down, lacks heel-toe progression in walking. Walking on their toes to avoid stumbling, knee is lifted up excessively also. All patients can walk on tiptoe, whereas 70% of patients were unable to walk on their heels. Muscle contractures were not observed before 8 years of age. Clinical Evolution Recurrent myalgias of the lower limbs occurred in time of motor performances (quadriceps muscle). Only one patient needed surgical orthopedic correction of bilateral anklebone blocking at 11 years of age (excessive valgus foot). In four of 10 adolescents no muscle shortening was observed. These patients performed physiotherapy until they walked unsupported, and later they continued playing sports (swimming). In the other six patients, neither physiotherapy nor sports were performed, and muscle shortening of the triceps surae and flexor hallucis longus were observed, with onset at the mean age of 12 years (range ⫽ 8-16 years of age). We observed that the spine position in scoliosis had become fixed at the same age in all patients. Shortening of lumbar muscles was very mild in all but one patient, who presented with moderate shortening at 27 years of age. Clinical history and neurologic examination of the parents was available in 27 of 39 kindreds. In 18 families the parents were normal, whereas in nine families (23%) joint hyperlaxity was detected, affecting both parents in two cases, only mothers in six cases, and only the father in one case. In seven parents with a long history of dynamic muscle activity no muscle shortening was observed. In four parents with sedentary life-style, muscle shortening was detected, causing limitations in their professional activities. In these parents shortening also involved the lumbar muscles with recurrent backache. In one parent (father) a lumbar disk prolapse was diagnosed at 28 years of age. Parents report the onset of lumbar pain at around the third decade, whereas the age of onset of triceps surae and flexor hallucis longus muscle shortening (foot equinus and cavus, respectively) remained unclear, and was presumably during childhood. Discussion
Standing In all patients we observed adduction of the shoulders and winged scapulae, spinal curvature accentuation, particularly hyperlordosis, abdominal protrusion, posture of the spine in non-fixed scoliosis, flat and valgus feet under
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Our long-term follow-up study confirms the good prognosis of congenital hypotonia with favorable outcome. High familial incidence in benign congenital hypotonia (30.2%) is reported [5], whereas the lower incidence we found is most likely because of the lack of information on
parents’ histories in 12 families. In fact, if we consider only the 27 kindreds in which clinical information and neurologic examinations were available, the familial incidence becomes higher (33.3%) and is similar to the incidence previously reported [5]. However, it is reported that the prevalence of joint hyperlaxity in the Western population is between 13.4% and 15.5%, with the preponderance in females [9]. We think the joint hyperlaxity described by orthopedic specialists in adolescents corresponds to the congenital hypotonia with favorable outcome described by pediatric neurologists in children. The various definitions could be caused by the different cultures of the two medical specialities, because pediatric neurologists usually focus their attention on muscles, whereas orthopedic specialists usually focus on joints. Taking this into consideration, we can assume that the prevalence of congenital hypotonia with favorable outcome is the same as that of joint hyperlaxity. An intriguing suggestion came from our data: in many cases a strong correlation between children with congenital hypotonia with favorable outcome and parents with a positive history of joint hyperlaxity was evident, as if joint hyperlaxity developed from congenital hypotonia with favorable outcome. In the past only sporadic observations have been made, including a child with benign congenital hypotonia with a family history of joint hyperlaxity in both parents [9], whereas in the other five patients, joint hyperlaxity was present only in one parent [5]. More recently, evolution of benign congenital hypotonia toward joint hyperlaxity in the same patient was observed. In a 23-year-old woman with generalized joint hyperlaxity and hip instability, benign congenital hypotonia was diagnosed at 5 weeks of age [10]. In fact, congenital hypotonia with favorable outcome gradually improves whereas joint hyperlaxity does not significantly diminish with aging [11]. We also observed a high frequency of patients who developed muscle shortening later on, especially among those who do not participate in sports, whereas the patients and parents who usually play sports were without muscular deficits. This finding might suggest that the hypotonic muscles observed (abdominal, anterior tibialis, and peroneus muscles), even if weak since birth, progressively became weaker because they were used insufficiently. In congenital hypotonia with favorable outcome the main muscles in the shortened position are lumbar muscles (hyperlordosis in standing up and walking), the triceps surae (foot equinus when it is not weight bearing and the patient is supine), and the flexor hallucis longus (foot cavus when it is not weight bearing). Abdominal, tibialis anterior, and peroneus muscles, as their antagonists, weaken later because of reduced use. These muscles could be the main targets of a physiotherapeutic treatment to prevent further deficits. In fact, stretching exercises and physiotherapy counteract the shortening of muscles. Active physiotherapy of weak muscles is useful because it
stretches the antagonist muscles that tend to shorten and preserves their strength. Until 8 years of age muscle shortening seems reversible. After this age it seems to become slowly irreversible, particularly for the triceps surae and flexor hallucis longus. Shortening of lumbar muscles seems to occur later. These three muscular segments tend to shorten because they work in shortened condition. For example, the triceps surae muscles work in shortening because joint hyperlaxity of the ankle tends to maintain the foot in plantar flexion (when sitting on the floor, almost all patients assume the “w” position of the lower limbs, with the bottom on the heels). In such a posture the feet are passively forced to maximum plantar flexing. Sitting on a chair, these patients dangle their feet, and even during walking the foot outload is maintained in passive equinus status and following slapped down. Furthermore, these patients tend to lift up their knee excessively instead of dorsiflexing the foot. As a consequence, most often the triceps muscles work in a shortened position and tend toward equinus. The mechanism of the shortening of the triceps surae muscles can be applied to other muscular groups (e.g., lumbar and flexor hallucis longus). Experimental findings provided a better understanding of the real structural changes occurring in shortening adaptation of the muscles. Striated muscle is a very adaptable tissue. In the shortened position, muscle fibers lose approximately 40% of the sarcomeres, and at their maximum length, muscle fibers produced 19% more sarcomeres [12,13]. Without neural influence the adjustment of sarcomere number seems to be a myogenic adaptation to the amount of passive tension to which the muscle is subjected [14]. The confusing term of muscle contracture [13], most often used by clinicians, could be a simple synonym of muscle shortening for sarcomere loss. Because the sarcomere number is adjusted to the functional length of the muscle, muscle hypoextensibility refers to a muscle adjusting its functional length in a shortened position over a long period of time. No other structural abnormalities were observed except an increase of connective tissue [13,14]. Muscle shortening does not define any characteristic muscle change except a reduction in sarcomere number. Considering these findings, we believe that the main cause of muscle shortening in our patients is caused by an increase in joint mobility that keeps muscles shortened in both the passive and active states for a long time. If this hypothesis is confirmed by other studies, continuous muscle exercise should be practiced as an active treatment to avoid muscular shortening. In fact, we noticed that all patients or parents that regularly practiced sports did not develop any kind of muscle shortening.
We thank Dr. Nicholas Kane for his helpful suggestions on earlier drafts of the manuscript.
Carboni et al: Congenital Hypotonia 385
References [1] Dubowitz V. The floppy infant. Clinics in developmental medicine, no. 76. 2nd ed. London: Spastics International Medical Publications, William Heinemann Medical Book, 1980:133-8. [2] Fardeau M, Tome FMS. Congenital muscular dystrophies: A breakthrough. Med Sci 1995;11:1679-84. [3] Grahame R. Joint hypermobility and genetic collagen disorders: Are they related? Arch Dis Child 1999;80:188-91. [4] Walton JN. Amyotonia congenita. A follow-up study. Lancet 1956;1:1023-8. [5] Shuper A, Wietz R, Varsano I, Mimouni M. Benign congenital hypotonia. A clinical study in 43 children. Eur J Pediatr 1987;146:360-2. [6] Joensen F. Benign kongenit hypotoni. Ugeskr-Laeger 1997;159: 1752-4. [7] Parush S, Yehezkehel I, Tenenbaum A, et al. Developmental correlates of school-age children with a history of benign congenital hypotonia. Dev Med Child Neurol 1998;40:448-52. [8] Benedetti P, Carboni P, Porro G, Spagnoli LG, Palmieri G. La
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biopsia muscolare mediante ago nella diagnosi delle malattie neuromuscolari in eta` pediatrica. Riv Ital Pediatr 1984;10:301-6. [9] Rikken-Bultman DG, Wellink L, van Dongen PW. Hypermobility in two Dutch school populations. Eur J Obstet Gynecol Reprod Biol 1997;73:189-92. [10] Paine RS. The future of “floppy infant”: A follow-up study of 133 patients. Dev Med Child Neurol 1963;5:115-24. [11] McGrory BJ, Burke DW, Moran SJ. Posterior instability of the hip in an adult. Clin Orthoped Rel Res 1997;341:151-4. [12] Tabary JC, Tabary C, Tardieu C, Tardieu G, Goldspink G. Physiological and structural changes in the cat’s soleus muscle due to immobilization at different lengths by plaster casts. J Physiol (Lond) 1972;224:231-44. [13] Tabary JC, Tardieu C, Tardieu G, Tabary C. Experimental rapid sarcomere loss with concomitant hypoextensibility. Muscle Nerve 1981;4:198-203. [14] Goldspink G, Tabary C, Tabary JC, Tardieu C, Tardieu G. Effect of denervation on the adaptation of sarcomere number and muscle extensibility to the functional length of the muscle. J Physiol (Lond) 1974;236:733-42.
From the *Department of Child Neuropsychiatric Science; University “La Sapienza”; Rome; †Child Neuropsychiatric Unit; University of Parma; Parma; ‡Pathology Service; “Regina Apostolorum Hospital”; Albano Laziale; Rome; and §Department of Orthopaedy; University “La Sapienza”; Rome, Italy.
© 2002 by Elsevier Science Inc. All rights reserved. PII S0887-8994(02)00379-X ● 0887-8994/02/$—see front matter
Introduction Infantile hypotonia is the clinical phenotype of several disorders involving different system, such as brain, muscle [1,2], and connective tissue [3], or metabolic pathways. Walton [4] first used the term benign congenital hypotonia to describe a clinical condition of neonatal hypotonia, excluding Werdnig-Hoffmann disease, with a good prognosis. However, with the development of myology, it has been proved that benign congenital hypotonia included many myopathies with structural or biochemical changes in the muscle fiber or in certain contractile proteins of skeletal muscle. However, many benign congenital hypotonia cases remain unclarified, even with detailed examination of the muscle. As a consequence, we prefer to avoid the confusing old nomenclature of benign congenital hypotonia, and instead prefer the more restrictive term of congenital hypotonia with favorable outcome. Nevertheless, irrespective of the cause, congenital hypotonia with favorable outcome has value as a descriptive term for patients fulfilling the criteria suggested by Walton for benign congenital hypotonia [5-7]: (1) early hypotonia, usually since birth; (2) active movements of the limbs and normal tendon reflexes; (3) normal or mild motor retardation that improves later on; (4) muscle enzymes at normal levels, normal results of electromyographic examination and nerve conduction studies (the last was added by us), and essentially normal muscle biopsy findings. Although congenital hypotonia with favorable outcome is most likely a syndrome with more than one etiology and mode of inheritance [5], the clinical presentation of these children is very similar. Congenital hypotonia with favorable outcome is a common problem in the pediatric practice, but its longterm clinical evolution and prognosis are not clearly defined in the literature. Furthermore, we were surprised to see the association of congenital hypotonia with favor-
Communications should be addressed to: Dr. Pisani; Servizio di Neuropsichiatria Infantile; Via Gramsci, 14; 43100 Parma, Italy. Received January 3, 2001; accepted December 18, 2001.
Carboni et al: Congenital Hypotonia 383
able outcome and muscle contracture in few children and joint hyperlaxity in some of their parents. We present a long-term follow-up study of congenital hypotonia with favorable outcome, which determines the relation between congenital hypotonia with favorable outcome and joint hyperlaxity, and discuss the probable mechanism underlying muscle contracture. Patients and Methods A longitudinal study of congenital hypotonia with favorable outcomeaffected children and their parents was conducted at the Department of Child Neuropsychiatric Sciences of the University “La Sapienza,” Rome, Italy, from 1985 through 2000. We studied the correlation between congenital hypotonia with favorable outcome and joint hyperlaxity. On the basis of Walton’s [4] parameters for congenital hypotonia with favorable outcome, 41 patients of 39 kindreds were selected, 25 of which were males and 16 were females (9 months to 12 years of age; mean, 6.7 years when needle muscle biopsy was performed). We used the following exclusion criteria: (1) children with delayed cognitive development or abnormal thyroid function; (2) children with a history of hypoxicischemic insult; (3) children without a full investigation for muscle diseases (muscle serum enzyme activities, electromyography, motor and sensory nerve conduction studies, muscle biopsy with histologic, histochemical, and electron-microscopic studies); and (4) children demonstrating abnormalities in the tests listed in item 3. In most cases, pediatricians sent the youngest patients to a neurologist for assessment of hypotonia and motor delay, whereas orthopedic specialists sent the older patients to a neurologist for assessment of joint hyperlaxity. At neurologic investigation in all patients in whom hypotonia was observed, needle muscle biopsy was performed [8]. Each specimen was cut into two samples. The first sample was snap-frozen, and cryostatic sections were submitted for morphologic and histoenzymatic studies (ATPase, NADH, SDH, and acid phosphatase), and the second sample was fixed in buffered gluteraldehyde solution for electron microscopy.
Results The laboratory tests and needle muscle biopsy results of the vastus lateralis were normal. Long-term follow-up demonstrated very good improvement on gross motor performances (e.g., the patients observed at 15 years of age walked and ran without problems). Patients with a familial etiology did not differ in clinical evolution from patients with a nonfamilial etiology. We report the clinical features of our patients in different postures (sitting, standing, and walking) and their clinical evolution. Sitting All patients easily assumed the “w” position of the lower limbs, with their bottom on their heels. In such a position the feet maintain an excessive clubfoot posture.
load, and enhancement of plantar arch (pes cavus) when the feet were not weight bearing. Gait The foot out load is maintained basically in passive equilibrium and after being slapped down, lacks heel-toe progression in walking. Walking on their toes to avoid stumbling, knee is lifted up excessively also. All patients can walk on tiptoe, whereas 70% of patients were unable to walk on their heels. Muscle contractures were not observed before 8 years of age. Clinical Evolution Recurrent myalgias of the lower limbs occurred in time of motor performances (quadriceps muscle). Only one patient needed surgical orthopedic correction of bilateral anklebone blocking at 11 years of age (excessive valgus foot). In four of 10 adolescents no muscle shortening was observed. These patients performed physiotherapy until they walked unsupported, and later they continued playing sports (swimming). In the other six patients, neither physiotherapy nor sports were performed, and muscle shortening of the triceps surae and flexor hallucis longus were observed, with onset at the mean age of 12 years (range ⫽ 8-16 years of age). We observed that the spine position in scoliosis had become fixed at the same age in all patients. Shortening of lumbar muscles was very mild in all but one patient, who presented with moderate shortening at 27 years of age. Clinical history and neurologic examination of the parents was available in 27 of 39 kindreds. In 18 families the parents were normal, whereas in nine families (23%) joint hyperlaxity was detected, affecting both parents in two cases, only mothers in six cases, and only the father in one case. In seven parents with a long history of dynamic muscle activity no muscle shortening was observed. In four parents with sedentary life-style, muscle shortening was detected, causing limitations in their professional activities. In these parents shortening also involved the lumbar muscles with recurrent backache. In one parent (father) a lumbar disk prolapse was diagnosed at 28 years of age. Parents report the onset of lumbar pain at around the third decade, whereas the age of onset of triceps surae and flexor hallucis longus muscle shortening (foot equinus and cavus, respectively) remained unclear, and was presumably during childhood. Discussion
Standing In all patients we observed adduction of the shoulders and winged scapulae, spinal curvature accentuation, particularly hyperlordosis, abdominal protrusion, posture of the spine in non-fixed scoliosis, flat and valgus feet under
384
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Vol. 26 No. 5
Our long-term follow-up study confirms the good prognosis of congenital hypotonia with favorable outcome. High familial incidence in benign congenital hypotonia (30.2%) is reported [5], whereas the lower incidence we found is most likely because of the lack of information on
parents’ histories in 12 families. In fact, if we consider only the 27 kindreds in which clinical information and neurologic examinations were available, the familial incidence becomes higher (33.3%) and is similar to the incidence previously reported [5]. However, it is reported that the prevalence of joint hyperlaxity in the Western population is between 13.4% and 15.5%, with the preponderance in females [9]. We think the joint hyperlaxity described by orthopedic specialists in adolescents corresponds to the congenital hypotonia with favorable outcome described by pediatric neurologists in children. The various definitions could be caused by the different cultures of the two medical specialities, because pediatric neurologists usually focus their attention on muscles, whereas orthopedic specialists usually focus on joints. Taking this into consideration, we can assume that the prevalence of congenital hypotonia with favorable outcome is the same as that of joint hyperlaxity. An intriguing suggestion came from our data: in many cases a strong correlation between children with congenital hypotonia with favorable outcome and parents with a positive history of joint hyperlaxity was evident, as if joint hyperlaxity developed from congenital hypotonia with favorable outcome. In the past only sporadic observations have been made, including a child with benign congenital hypotonia with a family history of joint hyperlaxity in both parents [9], whereas in the other five patients, joint hyperlaxity was present only in one parent [5]. More recently, evolution of benign congenital hypotonia toward joint hyperlaxity in the same patient was observed. In a 23-year-old woman with generalized joint hyperlaxity and hip instability, benign congenital hypotonia was diagnosed at 5 weeks of age [10]. In fact, congenital hypotonia with favorable outcome gradually improves whereas joint hyperlaxity does not significantly diminish with aging [11]. We also observed a high frequency of patients who developed muscle shortening later on, especially among those who do not participate in sports, whereas the patients and parents who usually play sports were without muscular deficits. This finding might suggest that the hypotonic muscles observed (abdominal, anterior tibialis, and peroneus muscles), even if weak since birth, progressively became weaker because they were used insufficiently. In congenital hypotonia with favorable outcome the main muscles in the shortened position are lumbar muscles (hyperlordosis in standing up and walking), the triceps surae (foot equinus when it is not weight bearing and the patient is supine), and the flexor hallucis longus (foot cavus when it is not weight bearing). Abdominal, tibialis anterior, and peroneus muscles, as their antagonists, weaken later because of reduced use. These muscles could be the main targets of a physiotherapeutic treatment to prevent further deficits. In fact, stretching exercises and physiotherapy counteract the shortening of muscles. Active physiotherapy of weak muscles is useful because it
stretches the antagonist muscles that tend to shorten and preserves their strength. Until 8 years of age muscle shortening seems reversible. After this age it seems to become slowly irreversible, particularly for the triceps surae and flexor hallucis longus. Shortening of lumbar muscles seems to occur later. These three muscular segments tend to shorten because they work in shortened condition. For example, the triceps surae muscles work in shortening because joint hyperlaxity of the ankle tends to maintain the foot in plantar flexion (when sitting on the floor, almost all patients assume the “w” position of the lower limbs, with the bottom on the heels). In such a posture the feet are passively forced to maximum plantar flexing. Sitting on a chair, these patients dangle their feet, and even during walking the foot outload is maintained in passive equinus status and following slapped down. Furthermore, these patients tend to lift up their knee excessively instead of dorsiflexing the foot. As a consequence, most often the triceps muscles work in a shortened position and tend toward equinus. The mechanism of the shortening of the triceps surae muscles can be applied to other muscular groups (e.g., lumbar and flexor hallucis longus). Experimental findings provided a better understanding of the real structural changes occurring in shortening adaptation of the muscles. Striated muscle is a very adaptable tissue. In the shortened position, muscle fibers lose approximately 40% of the sarcomeres, and at their maximum length, muscle fibers produced 19% more sarcomeres [12,13]. Without neural influence the adjustment of sarcomere number seems to be a myogenic adaptation to the amount of passive tension to which the muscle is subjected [14]. The confusing term of muscle contracture [13], most often used by clinicians, could be a simple synonym of muscle shortening for sarcomere loss. Because the sarcomere number is adjusted to the functional length of the muscle, muscle hypoextensibility refers to a muscle adjusting its functional length in a shortened position over a long period of time. No other structural abnormalities were observed except an increase of connective tissue [13,14]. Muscle shortening does not define any characteristic muscle change except a reduction in sarcomere number. Considering these findings, we believe that the main cause of muscle shortening in our patients is caused by an increase in joint mobility that keeps muscles shortened in both the passive and active states for a long time. If this hypothesis is confirmed by other studies, continuous muscle exercise should be practiced as an active treatment to avoid muscular shortening. In fact, we noticed that all patients or parents that regularly practiced sports did not develop any kind of muscle shortening.
We thank Dr. Nicholas Kane for his helpful suggestions on earlier drafts of the manuscript.
Carboni et al: Congenital Hypotonia 385
References [1] Dubowitz V. The floppy infant. Clinics in developmental medicine, no. 76. 2nd ed. London: Spastics International Medical Publications, William Heinemann Medical Book, 1980:133-8. [2] Fardeau M, Tome FMS. Congenital muscular dystrophies: A breakthrough. Med Sci 1995;11:1679-84. [3] Grahame R. Joint hypermobility and genetic collagen disorders: Are they related? Arch Dis Child 1999;80:188-91. [4] Walton JN. Amyotonia congenita. A follow-up study. Lancet 1956;1:1023-8. [5] Shuper A, Wietz R, Varsano I, Mimouni M. Benign congenital hypotonia. A clinical study in 43 children. Eur J Pediatr 1987;146:360-2. [6] Joensen F. Benign kongenit hypotoni. Ugeskr-Laeger 1997;159: 1752-4. [7] Parush S, Yehezkehel I, Tenenbaum A, et al. Developmental correlates of school-age children with a history of benign congenital hypotonia. Dev Med Child Neurol 1998;40:448-52. [8] Benedetti P, Carboni P, Porro G, Spagnoli LG, Palmieri G. La
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biopsia muscolare mediante ago nella diagnosi delle malattie neuromuscolari in eta` pediatrica. Riv Ital Pediatr 1984;10:301-6. [9] Rikken-Bultman DG, Wellink L, van Dongen PW. Hypermobility in two Dutch school populations. Eur J Obstet Gynecol Reprod Biol 1997;73:189-92. [10] Paine RS. The future of “floppy infant”: A follow-up study of 133 patients. Dev Med Child Neurol 1963;5:115-24. [11] McGrory BJ, Burke DW, Moran SJ. Posterior instability of the hip in an adult. Clin Orthoped Rel Res 1997;341:151-4. [12] Tabary JC, Tabary C, Tardieu C, Tardieu G, Goldspink G. Physiological and structural changes in the cat’s soleus muscle due to immobilization at different lengths by plaster casts. J Physiol (Lond) 1972;224:231-44. [13] Tabary JC, Tardieu C, Tardieu G, Tabary C. Experimental rapid sarcomere loss with concomitant hypoextensibility. Muscle Nerve 1981;4:198-203. [14] Goldspink G, Tabary C, Tabary JC, Tardieu C, Tardieu G. Effect of denervation on the adaptation of sarcomere number and muscle extensibility to the functional length of the muscle. J Physiol (Lond) 1974;236:733-42.