Floppy Infant

Fares Kokash,MD

Definition
Floppiness is a term used to describe babies who have marked muscle hypotonia.

 The focus of this talk is primarily on the diagnostic aspects, although we have not mentioned therapeutic aspects, these remain at the forefront.

Assessment
Prenatal risk factors:
History of drug or teratogen exposure Reduced fetal movements Presence of polyhydramnios Maternal diseases (diabetes, epilepsy) Parental age Consanguinity Family history of neuromuscular disease Other affected siblings

Assessment
Perinatal risk factors:
Birth trauma Birth anoxia Delivery complications Low APGAR scores (tone, reflexes and respiratory effort) Onset of the hypotonia Short umbilical cord (poor fetal movement or immobility) Abnormal fetal presentation (breech)

Clinical presentation of muscle hypotonia and weakness

Posture of full abduction and external rotation of the legs as well as a flaccid extension of the arms.

When traction is delivered to the arms, there is a prominent head lag. The presence of a typical myopathic facies and paucity of facial expression are common in hypotonic infants

Low-pitched cry / progressively weaker cry, readily distinguished from the vigorous cry of a normal infant. Paucity of antigravity movements

Differential Diagnosis
Differential Diagnosis: Upper Motor Neuron Causes Chromosomal Turner's Syndrome Down's Syndrome Prader-Willi Syndrome Infection Sepsis Meningitis Encephalitis Metabolic Hypocalcemia Hyponatremia Hypermagnesemia Hypoglycemia Hypothyroidism Aminoaciduria Gangliosidoses Hepatic Encephalopathy or Reye's Syndrome Toxin Drug Intoxication (e.g. Alcohol, Narcotic) Heavy metal poisoning Organophosphate Poisoning Anticholinergic exposure Perinatal trauma Perinatal asphyxia (HIE) Hemorrhage Differential Diagnosis: Lower Motor Neuron Causes Brainstem or spine Spinal muscular atrophy (Anterior Horn Cell Disorder) Infection Poliomyelitis Coxsackie Virus Neuromuscular Junction Congenital Myasthenia Gravis Myasthenic syndrome Botulism Neyve: -Guillain Barre Syndrome Muscle Muscular Dystrophy Congenital Myopathy Inflammatory Myopathy Other Tick Paralysis Benign congenital hypotonia

Localization of hypotonia and weakness

The neurological examination directs the clinician in localizing the site of the lesion to the
Central (UMN) Peripheral
lower motor unit (LMN) Neuromuscular junction muscles

UMN DTRs Muscle tone Muscle atrophy Fasciculation increased increased non non

LMN Decreased or absent decreased + +

Clinical characteristics of muscle hypotonia and weakness

Central hypotonia
Weakness is uncommon except in the acute stages, and usually it is axial weakness obtundation and depressed level of consciousness Hyperreflexia

Infants with severe CNS abnormalities develop signs of hypotonia in addition to

impairment in level of consciousness feeding difficulties seizures apneas abnormal posturing abnormalities of ocular movements and of brain stem reflexes

Clinical characteristics of muscle hypotonia and weakness

Disorders of LMN
The presence of profound weakness as well as hypo/areflexia

Clinical characteristics of muscle hypotonia and weakness

neuromuscular disease
Infants are visually quite alert combination of weakness in the antigravity limb muscles and hypo/areflexia together Involvement of bulbar and occulomotor muscles

Clinical characteristics of muscle hypotonia and weakness

Such a clear distinction, however, may not always be possible and the features may overlap in conditions where the pathology affects both the CNS and peripheral nerve (PelizaeusMerzbacher disease, leukodystrophies)

The presence of characteristic patterns of regional weakness may favor certain etiologies

Additional clinical clues to differential diagnosis

A high arched palate is often noted in infants with neuromuscular disorders the tongue may be large in storage disorders (acid maltase/Pompe disease) the presence of tongue fasciculation suggests anterior horn cell involvement and denervation Visceral enlargement (suggests storage disorders) inverted nipples (congenital disorders of glycosylation)

Additional clinical clues to differential diagnosis

Ptosis, external ophthalmoplegia (myasthenic syndromes) Cataracts, renal cysts, pigmentary retinopathy (peroxisomal disorders) Lens dislocation (sulfite oxidase/molybdenum cofactor deficiency)

Additional clinical clues to differential diagnosis

Arthrogryposis: the presence of severe weakness in early fetal development, which immobilizes joints, resulting in contractures. This can be a feature encountered in both neurogenic and myopathic disorders.

Neurogenic disorders are associated with a higher incidence of other congenital anomalies Myopathic features are less likely to be associated with other defects.

Laboratory investigations
Appropriate and cost effective use of laboratory investigations to establish a specific etiologic diagnosis is always desirable. The history and physical assessment will point out the possible etiology and the indications for relevant diagnostic tests.

Evaluation of central CNS disorders

Brain MRI EEG Genetic tests Infection screen CSF neurotransmitters

Evaluation of motor unit disorders

DNA-based testing Edrophonium chloride Electrodiagnosis
EMG NCS Repetitive stimulation

Muscle biopsy Nerve biopsy Serum CK

Laboratory investigations
We suggest a systematic approach based on the tests currently utilized in the evaluation of infants with hypotonia:
infants with pure hypotonia of central or peripheral origin infants with hypotonia and multisystem features (hypotonia plus)

 infants with pure hypotonia of central or peripheral origin

 infants with hypotonia and multisystem features (hypotonia plus)

Etiological considerations

1. 2. 3.
1. 2.

Central Nervous System:

Chromosomal disorders Metabolic inborn errors Structural CNS malformations
congenital malformations (lissencephaly, holoprosencephaly) acquired disorders (birth trauma, hypoxic ischemic encephalopathy)

1.

Periphral Nervous System

Motor neuron disorders:
SMA

1.

Disorders of peripheral nerves:

Peripheral neuropathies

1. 2. 3.

Disorders of the neuromuscular junction:

Myathenia Syndromes:congenital,transient Infantile botulism Neonatal hypermagnesemia

1. 2. 3. 4.

Disorders with prominent muscle involvement:

Congenital myopathies Congenital muscular dystrophies Metabolic myopathies Congenital myotonic dystrophy

Chromosomal abnormalities

Etiological considerations

1. 2. 3.
1. 2.

Central Nervous System:

Chromosomal disorders Metabolic inborn errors Structural CNS malformations
congenital malformations (lissencephaly, holoprosencephaly) acquired disorders (birth trauma, hypoxic ischemic encephalopathy)

1.

Periphral Nervous System

Motor neuron disorders:
SMA

1.

Disorders of peripheral nerves:

Peripheral neuropathies

1. 2. 3.

Disorders of the neuromuscular junction:

Myathenia Syndromes:congenital,transient Infantile botulism Neonatal hypermagnesemia

1. 2. 3. 4.

Disorders with prominent muscle involvement:

Congenital myopathies Congenital muscular dystrophies Metabolic myopathies Congenital myotonic dystrophy

Metabolic disorders presenting with severe hypotonia in infancy

Etiological considerations

1. 2. 3.
1. 2.

Central Nervous System:

Chromosomal disorders Metabolic inborn errors Structural CNS malformations
congenital malformations (lissencephaly, holoprosencephaly) acquired disorders (birth trauma, hypoxic ischemic encephalopathy)

1.

Periphral Nervous System

Motor neuron disorders:
SMA

1.

Disorders of peripheral nerves:

Peripheral neuropathies

1. 2. 3.

Disorders of the neuromuscular junction:

Myathenia Syndromes:congenital,transient Infantile botulism Neonatal hypermagnesemia

1. 2. 3. 4.

Disorders with prominent muscle involvement:

Congenital myopathies Congenital muscular dystrophies Metabolic myopathies Congenital myotonic dystrophy

Structural CNS malformations/encephalopathies

This category includes:

congenital malformations of the nervous system (lissencephaly, holoprosencephaly) In the majority of instances in this group of disorders, hypotonia is rarely the sole feature at presentation (other features such as seizures, craniofacial dysmorphisms) acquired disorders (birth trauma, hypoxic ischemic encephalopathy) that are associated with profound hypotonia in the neonatal period.

Etiological considerations

1. 2. 3.
1. 2.

Central Nervous System:

Chromosomal disorders Metabolic inborn errors Structural CNS malformations
congenital malformations (lissencephaly, holoprosencephaly) acquired disorders (birth trauma, hypoxic ischemic encephalopathy)

1.

Periphral Nervous System

Motor neuron disorders:
SMA

1.

Disorders of peripheral nerves:

Peripheral neuropathies

1. 2. 3.

Disorders of the neuromuscular junction:

Myathenia Syndromes:congenital,transient Infantile botulism Neonatal hypermagnesemia

1. 2. 3. 4.

Disorders with prominent muscle involvement:

Congenital myopathies Congenital muscular dystrophies Metabolic myopathies Congenital myotonic dystrophy

Disorders affecting motor neuron and peripheral nerves

Motor neuron disorders

Spinal muscular atrophy (WerdnigHoffman disease):
is AR disorder involving the degeneration of the anterior horn cells hypotonic and weak, at birth or soon after poverty of spontaneous movements abnormal posture typical for a floppy infant tongue fasciculation and absent deep tendon reflexes, mild contractures and decreased fetal movements before birth the weakness usually involves the bulbar and respiratory muscles, causing significant respiratory distress and infants develop pneumonia and respiratory failure.

The diagnosis is often clinical

EMG usually shows spontaneous fibrillation potentials at rest Muscle biopsy shows grouped neurogenic atrophy and evidence of presence of hypertrophic type I myofibres (rennervation) DNA based molecular diagnostic tests

Etiological considerations

1. 2. 3.
1. 2.

Central Nervous System:

Chromosomal disorders Metabolic inborn errors Structural CNS malformations
congenital malformations (lissencephaly, holoprosencephaly) acquired disorders (birth trauma, hypoxic ischemic encephalopathy)

1.

Periphral Nervous System

Motor neuron disorders:
SMA

1.

Disorders of peripheral nerves:

Peripheral neuropathies

1. 2. 3.

Disorders of the neuromuscular junction:

Myathenia Syndromes:congenital,transient Infantile botulism Neonatal hypermagnesemia

1. 2. 3. 4.

Disorders with prominent muscle involvement:

Congenital myopathies Congenital muscular dystrophies Metabolic myopathies Congenital myotonic dystrophy

Disorders of the neuromuscular junction

The following disorders affecting the neuromuscular junction can be considered in the differential diagnoses of the floppy infant: congenital myasthenic syndromes Transient myasthenic syndrome Hypermagnesemia of the newborn Infantile botulism

myasthenia syndrome
Infants presenting with the myasthenia syndrome share several features including:
hypotonia facial diplegia ptosis feeding difficulties apnea respiratory difficulties generalized weakness progressively weakening cry

Congenital myasthenic syndrome

Transient myasthenic syndrome

The disorder occurs in infants born to mothers with myasthenia gravis. The acetylcholine receptor (AchR) antibody that causes MG crosses the placenta and exerts a blocking effect that is responsible for the interference with neuromuscular transmission. The symptoms caused are temporary and recovers in about 6 weeks.

Hypermagnesemia of the newborn

Elevated magnesium levels can be encountered in the newborn following

treatment of maternal eclampsia with magnesium sulfate or use of magnesium antacids in the newborn

Clinically: encephalopathic infant with hypotonia, depressed deep tendon reflexes, abdominal distension due to ileus and irregularities of cardiac rhythm. Elevated magnesium levels result in impaired neuromuscular transmission.

Infantile botulism
usually occurs within 6 weeks to 1 year after birth usually in situations where the infant has been fed honey contaminated with spores of the C. botulinum. The first symptom is usually constipation. Later, listlessness, ptosis, facial weakness, decreased eye movements and feeding difficulties, and progression to respiratory failure occur. rapid repetitive stimulation : presence of small amplitude motor potentials and an incremental response noted to is pathognomonic. Stool study may also be helpful in confirmation, but the results are usually delayed.

Etiological considerations

1. 2. 3.
1. 2.

Central Nervous System:

Chromosomal disorders Metabolic inborn errors Structural CNS malformations
congenital malformations (lissencephaly, holoprosencephaly) acquired disorders (birth trauma, hypoxic ischemic encephalopathy)

1.

Periphral Nervous System

Motor neuron disorders:
SMA

1.

Disorders of peripheral nerves:

Peripheral neuropathies

1. 2. 3.

Disorders of the neuromuscular junction:

Myathenia Syndromes:congenital,transient Infantile botulism Neonatal hypermagnesemia

1. 2. 3. 4. 5.

Disorders with prominent muscle involvement:

Congenital myopathies Congenital muscular dystrophies Metabolic myopathies Congenital myotonic dystrophy Endocrine myopathies

Muscular dystrophies Course progressive weakness and wasting significantly elevated

Congenital myopathies non-progressive or slowly progressive normal or slightly elevated

CK

Muscular dystrophies

Congenital myopathies

Conclusions
The practicing clinician faced with the challenge of making a diagnosis in a floppy infant needs to be aware of
the various etiologies availability of specific diagnostic tests the role of supportive investigations

in order to facilitate this process in a speedy and cost effective way.

Conclusions
A detailed history and physical examination can help sort the issue of isolated hypotonia, from the hypotonic/dysmorphic infant with multisystem manifestations.

Conclusions
The floppy infant poses a chronic neurological problem demanding multidisciplinary skills and support for both diagnosis and management.

Conclusions
Establishing a specific diagnosis in each case is important
anticipated outcome for the condition genetic counselling (parents and family members).