Evaluation of the floppy infant

GGC Paediatric Guidelines
NHS GGC

Objectives

This guideline is intended to guide the investigation of babies with unanticipated floppiness in the neonatal period.  Users should refer to appropriate guidance where the cause is known, including guidance on HIE, hypoglycaemia, sepsis and other systemic illnesses.  Users should also refer to relevant drug monographs.

The word floppy can be used to mean:

  • Decrease in muscle tone (hypotonia)
  • Decrease in muscle power (weakness)
  • Ligamentous laxity and increased range of joint mobility.

Hypotonia: definition of tone

It is the resistance to passive movement around the joint.

  • Phasic tone: assessed by the response of the muscle to a rapid stretch (tendon reflexes).
  • Postural tone: measured by the response of the muscle to a sustained low-intensity stretch (maintaining posture against gravity= significant head lag on pull-to-sit, rag-doll posture on ventral suspension, slipping through the hands when the infant is held under the arms).

History

  • Antenatal history of reduced fetal movement, or polyhydramnios.
  • Family history of muscle disease, stillbirth or consanguinity.
  • Delivery, resuscitation, Apgar scores and cord gases
  • History since delivery: respiratory effort, ability to feed, level of alertness, level of spontaneous activity and character of cry.

Diagnostic approach

NB - It is important to exclude systemic illness such as sepsis, hypoglycaemia etc.

It is important to determine whether the problem is of an upper motor neurone type (central hypotonia), or of a lower motor neurone type (peripheral hypotonia).  In the neonatal period, central causes account for two-thirds of cases with HIE being the most common.

Indicators of Central hypotonia

Indicators of  Peripheral hypotonia
  • Normal strength (Normal antigravity movements).
  • Dysmorphic features.
  • Normal or brisk tendon reflexes.
  • Irritability +/- loud cry.
  • History suggestive of HIE, Birth Trauma, or symptomatic hypoglycaemia.
  • Seizures.
  • Reduced strength (reduced or absent spontaneous anti-gravity movements).
  • Reduced or absent reflexes.
  • Muscle fasciculation (rarely seen but very important if seen).
  • Myopathic face (open mouth with tented upper lip, poor lip seal when sucking, lack of facial expression, ptosis).
  • Weak cry.
  • Look bright.
  • Note that during the acute stage of some central causes the infant may appear weak.
  • Some of the congenital muscular dystrophies are associated with brain malformations.
  • Metabolic causes and those which are multi-system diseases can be difficult to differentiate central from peripheral.
  • Babies with profound central hypotonia may have absent deep tendon reflexes.
  • contractures are a clue to a muscle cause in a floppy child

Causes of hypotonia

Central hypotonia

Peripheral hypotonia

1.    Acute Encephalopathies:

  • HIE (hypoxic ischaemic encephalopathy).
  • Hypoglycaemia.
  • Intracranial haemorrhage.

2.    Chronic Encephalopathies:

  • Cerebral malformations.
  • Inborn errors of metabolism   (mucopolysaccharidoses, aminoacidurias, organic acidurias, lipidoses, glycogen–storage diseases, Menkes syndrome).
  • Chromosomal disorders (Prader-Willi syndrome, Trisomy 21).
  • Peroxisomal disorders ( neonatal adrenoleukodystrophy, Zellwegers syndrome),
  • Endocrine (hypothyroidism).
  • Metabolic (renal tubular acidosis).

3.    Connective Tissue disorders:

  • Ehlers-Danlos syndrome.
  • Osteogenesis imperfecta.
  • Congenital Ligamentous laxity.

1.    Spinal cord:

  • Spinal Cord.
  • Syringomyelia.

2.    Anterior horn cell:

  • SMA (spinal muscular atrophy).
  • Pompe’s disease (acid maltase deficiency).

3.    Neuro-muscular junction:

  • Myasthenia gravis (transient, congenital autoimmune).
  • Infantile botulism.

4.    Muscular disorders:

  • Congenital muscular dystrophies (CMD) ( Walker-Warburg, Fukuyama, Muscle-eye-brain disease, merosin-positive CMD)
  • Congenital myopathies (nemaline rod myopathy, myotubular myopathies, central core disease, minicore disease).
  • Congenital myotonic dystrophy.

5.    Peripheral nerves:

  • Hereditary motor and sensory neuropathy (HMSN).
  • Congenital hypomyelination neuropathy.

6.    Metabolic myopathies:

  • Acid maltase deficiency.
  • Carnitine deficiency.
  • Mitochondrial (cytochrome-c-oxidase deficiency.

7. Arthrogryposis

Investigations

Central hypotonia

Peripheral hypotonia

First line Investigations:

  • Serum electrolytes, glucose, calcium, Magnesium and phosphate, liver function test, thyroid function test, blood gases, Lactate and ammonia.
  • Septic screen including lumbar puncture with CSF goes to both bacteriology and virology.
  • Plasma amino acids.
  • Urine for organic acids.
  • Neuroimaging: USS head.
  • Microarray CGH

Second Line Investigations:

  •  MRI, EEG has prognostic information for brain function.
  • Urine for
    mucopolysaccharide screen= GAG (glycosaminoglycan)
  • Very long chain fatty acids.
  • Screen for congenital viral infections.
  • Consider medical genetics and ophthalmology opinion.
  • Consider plasma copper and caeruloplasmin assay(for Menkes)
  • Acylcarnitine profile (plasma or blood spot test).
  • consider a blood spot to biochemistry  for acid maltase

First Line Investigations

  • Creatine kinase (levels need to be interpreted with caution as tend to be higher at birth, rises in the first 24 hours, and increase with acidosis) so if initial test is high, repeat.
  • DNA for myotonic dystrophy.
  • Genetic testing for SMA gene deletion which is present in 95% of cases of SMA type 1.
  • EDTA sample for Prader-Willi testing
  • CXR/ECHO (cardiomegaly/cardiomyopathy).
  • Microarray CGH

Second Line Investigations

  • Neurology service: EMG/NCS (nerve conduction studies), may distinguish between neurogenic, myopathic, myotonic and myasthenic aetiologies, although difficult in the first 6 months of life.
  • Muscle biopsy: to be sent for histology, immunohistochemistry, electron microscopy, respiratory chain enzyme analysis).

*NB – If a diagnosis of congenital myaesthenia gravis is considered it is considered best practice to perform an EMG before considering a challenge with pyridostigmine.  If such a challenge is undertaken the appropriate dosage would be:-

Pyridostigmine  -

1 milligram/kg/day in 6 divided doses, increasing by weekly increments of 1mg/kg/day - up to a maximum 4 mg/kg/day

once at the maximum dose of 4 mg/kg/day, continue the dose for 6 weeks to assess response.

 

Additional clues which may direct to a specific diagnosis

  • Hepatosplenomegaly; storage disorders, congenital infections.
  • Renal cysts, high forehead and wide fontanelles; Zellweger’s syndrome.
  • Hepatomegaly, retinitis pigmentosa; neonatal adrenoleukodystrophy.
  • Congenital cataracts, glaucoma; oculocerebrorenal (Lowe) syndrome.
  • Abnormal odour; metabolic disorders.
  • Hypopigmentation, undescended testes; Prader Willi

Principles of Management

  • Physiotherapy: stretches aimed at prevention of contractures, positioning.
  • Respiratory support.
  • Feeding.
  • Management of gastro-oesophageal reflux.
  • Evaluation and treatment of cardiac dysfunction.
  • Later:
    Prevention and correction of scoliosis.
    Prevention and prompt treatment of respiratory infections.
    Follow up of general development and stimulation of learning.
  • Please note that with advances in treatment of SMA and potential gene therapy in DMD, early diagnosis as initiation of early treatment as early as possible is recommended for individuals with infantile-onset (Type 1) and pre-symptomatic SMA

Editorial Information

Last reviewed: 08/08/2019

Next review date: 01/08/2022

Author(s): Dr Nashwa Matta – Associate Specialist in neonatology – PRM.

Approved By: West of Scotland Managed Clinical Network for Neonatology

References