Updates in Floppy Infant Syndrome
Heba Hatem Salah;
Abstract
The term ‘floppy baby or infant’ is used to denote an infant with poor muscle tone affecting the limbs, trunk and the cranio–facial musculature. The condition is usually evident at birth or is identified during early life as poor muscle tone results in an inability to maintain normal posture during movement and rest.
Muscle tone is maintained at the peripheral level by participation of the fusimotor system: pathways involving the muscle spindles that promote musclecontraction in response to stretch and the inverse myotactic reflex involving the Golgi tendon organ that provides a braking mechanism to the contraction of muscles. A lesion interrupting the stretch reflexes at any level in the lower motor neuron (LMN) will result in a loss of muscle toneand stretch reflexes i.e. flaccidity. The output of gamma motor neurons to the muscle spindle is influenced by supraspinal influences, which are predominantly inhibitory; thus lesions affecting the upper motor neuron (UMN) result in the reduction of these inhibitory influences, in turn causing an increase in excitatory output of the gamma motor neurons to the muscle spindle4. However, in early infancy, contrary to the expected increase in muscletone, the response to an UMN lesion in the early stages is flaccidity and loss of muscle tone. This pattern of hypotonia is usually associated with preserved or hyperactive reflexes and later evolves into spasticity.
Floppy infants may be due to central hypotonia or hypotonia of neuromuscular origin.
Central hypotonia includes chromosomal disorders, genetic disorders, brain dysgenesis, acute hemorrhagic or other brain injuries, hypoxic encephalopathy, peroxisomal disorders, metabolic defects, drug intoxications and benign congenital hypotonia. Peripheral hypotonia includes Werding Hoffman disease, poliomyelitis, neonatal Guillan-Barre syndrome, myasthenia gravies, Pomp disease, and muscle disorders. In certain cases, however, central and peripheral defects coexist as in congenital myotonic dystrophy, congenital muscular dystrophy, lipid storage diseases, and mitochondrial encephalomyopathies.
Once an infant presents, the most important aspect is the history to guide one to a possible etiological diagnosis. Antenatal, natal and postnatal histories are important aspects that need attention.
The incidence of breech presentation is higher in fetuses with neuromuscular disorders as turning requires adequate fetal mobility. Documentation of birth trauma, birth anoxia, delivery complications, low cord pH and Apgar scores are crucial as hypoxic-ischaemic encephalopathy remains an important cause of neonatal hypotonia. Neonatal seizures and an encephalopathic state offer further proof that the hypotonia is of central origin.
Onset of the hypotonia is also important as it may distinguish between congenital and acquired etiologies. Family history is another important component in the history with consanguinity of parents and siblings with a similar illness. Early deaths / stillbirths and drawing a family tree /pedigree would be helpful for future genetic counseling.
The physical examination should include the assessment of clinical features (eg, the presence of fixed deformities), a comprehensive neurologic evaluation, and an assessment for dysmorphic features. The diagnosis of myotonic dystrophy in a floppy newborn is suggested by a history of uterine dystonia and a difficult delivery, as well as by examination of the handshake of the mother, who demonstrates an inability to relax her hand. Clinical evaluation includes a detailed neurologic assessment examining tone, strength, and reflexes. To begin assessing tone, a clinician should examine an infant’s head size and shape, posture, and movement. A floppy infant often lies with limbs abducted and extended. Plagiocephaly frequently is present. Additional techniques for positioning and examining tone include horizontal and vertical suspension and traction.
Three features are generally useful in establishing the locus of hypotonia at anatomical level above the lower motor neuron, first, hypotonia is usually more severe than weakness and, in dead, some affected infants although "floppy" exhibit strong movements when stimulated. Second, tendon reflexes are usually preserved, although it is unusual to observe the hall mark of central hypotonia as seen after the first weeks and months of life: hyperactive tendon reflex. Thus, as with weakness hypotonia is more marked than is involvement of tendon reflex. Third, other signs of central involvement are frequently present, particular note: should be made of seizure.
Scissoring are early signs of spasticity and indicate cerebral dysfunction. Eliciting postural reflexes in newborns and infants when spontaneous movement is lacking indicates cerebral hypotonia. In some acute encephalopathies, and especially in metabolic disorders, the Moro reflex may be exaggerated.
Initial laboratory evaluation of the hypotonic newborn is directed at ruling out systemic disorders. Routine studies should include evaluation for sepsis (blood culture, urine culture, cerebrospinal fluid culture and analysis); measurement of serum electrolytes, liver functions, ammonia, glucose, calcium, magnesium, and creatinine; a complete blood count; and a urine drug screen.
Muscle enzymes (creatine kinase assay) are rarely helpful in the floppy infant, with the exception of muscle disorders where creatine kinase values are elevated (CMD and in some forms of the congenital myopathies).
If the hypotonia is considered to be central, the patients should be investigated with magnetic resonance imaging (MRI) of the brain/computer tomography (CT) brain. These are helpful in the identification of structural malformations, neuronal migration defects.
Magnetic resonance spectroscopy (proton-MRS) permits the non-invasive assessment of neuronal integrity (N-acetyl aspartate peaks), intracerebral accumulation of unusual metabolites (lactate, glycine) or the deficiency of a key metabolite (creatine deficiency).
The technique of electroneuromyography (EMG/nerve conduction study) retains relevance in the investigation of disorders of the lower motor unit.
Studies of nerve conduction velocity are useful in distinguishing axonal from demyelinating neuropathies. Demyelinating neuropathies cause greater slowing of conduction velocity. Repetitive nerve stimulation studies demonstrate disturbances in neuromuscular transmission.
Muscle biopsy with immunohistochemical staining and electron microscopy is the method of choice for differentiating myopathies and muscular dystrophies, although it is more invasive.
Muscle biopsy should be considered in the diagnosis of suspected myopathies and muscular dystrophies, even if the electrophysiological studies are normal. If biopsy shows specific abnormalities, it can be an essential part of the diagnostic evaluation in the newborn to guide subsequent DNA molecular diagnostic studies.
The karyotype will disclose any obvious cytogenetic defects such as chromosomal duplications, deletions and trisomies such as Down syndrome (DS, trisomy 21) at a standard 500 band level. The use of multiple telomericfluorescent in-situ hybridization (FISH) probes as well as newer techniques of automated fluorescent genotyping will make it easier to pick up microdeletions and disomies that cannot be detected by conventional cytogenetics.
Newer cytogenetic tests such as array comparative genomic hybridization (array CGH) and second generation sequencing studies (exome sequencing) will enhance and facilitate the genetic investigation of hypotonia. The detection rate for chromosomal abnormalities with array CGH with a normal karyotype is in the range of 5-17%, a significant improvement. That being said, array CGH is a powerful diagnostic tool and is replacing conventional cytogenetics, as well as other labour-intensive techniques such as fluorescent in-situ hybridization (FISH) and mutli-telomeric FISH.
Exone sequencing is likely to be a reasonable and effective tool to determine disease-causing variants underlying monogenic disorders.
Treatment of the infant who has hypotonia must be tailored to the specific responsible condition. In general, therapy is supportive. Rehabilitation is an important therapeutic consideration, with the aid of physical and occupational therapists. Nutrition is of primary importance to maintain ideal body weight for the age and sex which is often achieved through the nasogastric route or percutaneous gastrostomy.
Muscle tone is maintained at the peripheral level by participation of the fusimotor system: pathways involving the muscle spindles that promote musclecontraction in response to stretch and the inverse myotactic reflex involving the Golgi tendon organ that provides a braking mechanism to the contraction of muscles. A lesion interrupting the stretch reflexes at any level in the lower motor neuron (LMN) will result in a loss of muscle toneand stretch reflexes i.e. flaccidity. The output of gamma motor neurons to the muscle spindle is influenced by supraspinal influences, which are predominantly inhibitory; thus lesions affecting the upper motor neuron (UMN) result in the reduction of these inhibitory influences, in turn causing an increase in excitatory output of the gamma motor neurons to the muscle spindle4. However, in early infancy, contrary to the expected increase in muscletone, the response to an UMN lesion in the early stages is flaccidity and loss of muscle tone. This pattern of hypotonia is usually associated with preserved or hyperactive reflexes and later evolves into spasticity.
Floppy infants may be due to central hypotonia or hypotonia of neuromuscular origin.
Central hypotonia includes chromosomal disorders, genetic disorders, brain dysgenesis, acute hemorrhagic or other brain injuries, hypoxic encephalopathy, peroxisomal disorders, metabolic defects, drug intoxications and benign congenital hypotonia. Peripheral hypotonia includes Werding Hoffman disease, poliomyelitis, neonatal Guillan-Barre syndrome, myasthenia gravies, Pomp disease, and muscle disorders. In certain cases, however, central and peripheral defects coexist as in congenital myotonic dystrophy, congenital muscular dystrophy, lipid storage diseases, and mitochondrial encephalomyopathies.
Once an infant presents, the most important aspect is the history to guide one to a possible etiological diagnosis. Antenatal, natal and postnatal histories are important aspects that need attention.
The incidence of breech presentation is higher in fetuses with neuromuscular disorders as turning requires adequate fetal mobility. Documentation of birth trauma, birth anoxia, delivery complications, low cord pH and Apgar scores are crucial as hypoxic-ischaemic encephalopathy remains an important cause of neonatal hypotonia. Neonatal seizures and an encephalopathic state offer further proof that the hypotonia is of central origin.
Onset of the hypotonia is also important as it may distinguish between congenital and acquired etiologies. Family history is another important component in the history with consanguinity of parents and siblings with a similar illness. Early deaths / stillbirths and drawing a family tree /pedigree would be helpful for future genetic counseling.
The physical examination should include the assessment of clinical features (eg, the presence of fixed deformities), a comprehensive neurologic evaluation, and an assessment for dysmorphic features. The diagnosis of myotonic dystrophy in a floppy newborn is suggested by a history of uterine dystonia and a difficult delivery, as well as by examination of the handshake of the mother, who demonstrates an inability to relax her hand. Clinical evaluation includes a detailed neurologic assessment examining tone, strength, and reflexes. To begin assessing tone, a clinician should examine an infant’s head size and shape, posture, and movement. A floppy infant often lies with limbs abducted and extended. Plagiocephaly frequently is present. Additional techniques for positioning and examining tone include horizontal and vertical suspension and traction.
Three features are generally useful in establishing the locus of hypotonia at anatomical level above the lower motor neuron, first, hypotonia is usually more severe than weakness and, in dead, some affected infants although "floppy" exhibit strong movements when stimulated. Second, tendon reflexes are usually preserved, although it is unusual to observe the hall mark of central hypotonia as seen after the first weeks and months of life: hyperactive tendon reflex. Thus, as with weakness hypotonia is more marked than is involvement of tendon reflex. Third, other signs of central involvement are frequently present, particular note: should be made of seizure.
Scissoring are early signs of spasticity and indicate cerebral dysfunction. Eliciting postural reflexes in newborns and infants when spontaneous movement is lacking indicates cerebral hypotonia. In some acute encephalopathies, and especially in metabolic disorders, the Moro reflex may be exaggerated.
Initial laboratory evaluation of the hypotonic newborn is directed at ruling out systemic disorders. Routine studies should include evaluation for sepsis (blood culture, urine culture, cerebrospinal fluid culture and analysis); measurement of serum electrolytes, liver functions, ammonia, glucose, calcium, magnesium, and creatinine; a complete blood count; and a urine drug screen.
Muscle enzymes (creatine kinase assay) are rarely helpful in the floppy infant, with the exception of muscle disorders where creatine kinase values are elevated (CMD and in some forms of the congenital myopathies).
If the hypotonia is considered to be central, the patients should be investigated with magnetic resonance imaging (MRI) of the brain/computer tomography (CT) brain. These are helpful in the identification of structural malformations, neuronal migration defects.
Magnetic resonance spectroscopy (proton-MRS) permits the non-invasive assessment of neuronal integrity (N-acetyl aspartate peaks), intracerebral accumulation of unusual metabolites (lactate, glycine) or the deficiency of a key metabolite (creatine deficiency).
The technique of electroneuromyography (EMG/nerve conduction study) retains relevance in the investigation of disorders of the lower motor unit.
Studies of nerve conduction velocity are useful in distinguishing axonal from demyelinating neuropathies. Demyelinating neuropathies cause greater slowing of conduction velocity. Repetitive nerve stimulation studies demonstrate disturbances in neuromuscular transmission.
Muscle biopsy with immunohistochemical staining and electron microscopy is the method of choice for differentiating myopathies and muscular dystrophies, although it is more invasive.
Muscle biopsy should be considered in the diagnosis of suspected myopathies and muscular dystrophies, even if the electrophysiological studies are normal. If biopsy shows specific abnormalities, it can be an essential part of the diagnostic evaluation in the newborn to guide subsequent DNA molecular diagnostic studies.
The karyotype will disclose any obvious cytogenetic defects such as chromosomal duplications, deletions and trisomies such as Down syndrome (DS, trisomy 21) at a standard 500 band level. The use of multiple telomericfluorescent in-situ hybridization (FISH) probes as well as newer techniques of automated fluorescent genotyping will make it easier to pick up microdeletions and disomies that cannot be detected by conventional cytogenetics.
Newer cytogenetic tests such as array comparative genomic hybridization (array CGH) and second generation sequencing studies (exome sequencing) will enhance and facilitate the genetic investigation of hypotonia. The detection rate for chromosomal abnormalities with array CGH with a normal karyotype is in the range of 5-17%, a significant improvement. That being said, array CGH is a powerful diagnostic tool and is replacing conventional cytogenetics, as well as other labour-intensive techniques such as fluorescent in-situ hybridization (FISH) and mutli-telomeric FISH.
Exone sequencing is likely to be a reasonable and effective tool to determine disease-causing variants underlying monogenic disorders.
Treatment of the infant who has hypotonia must be tailored to the specific responsible condition. In general, therapy is supportive. Rehabilitation is an important therapeutic consideration, with the aid of physical and occupational therapists. Nutrition is of primary importance to maintain ideal body weight for the age and sex which is often achieved through the nasogastric route or percutaneous gastrostomy.
Other data
| Title | Updates in Floppy Infant Syndrome | Other Titles | الحديث فى متلازمـة حديث الـولادة الرخـوى | Authors | Heba Hatem Salah | Issue Date | 2015 |
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