Flat baby
Further neurological investigations are indicated when the aetiology is not clearly asphyxia, trauma, infection or poisoning.
Contributory causes include myotonic dystrophy and some congenital myopathies, glycine encephalopathy, mitochondrial derangements, Aicardi-Goutieres syndrome and the central hypoventilation syndrome.
Apnoeic baby
Apnoea could be feature of subtle neonatal epileptic seizures
Myasthenia
A response to edrophonium or neostigmine or a positive result on stimulation single fibre EMC (stimSFEMG) should confirm this.
Hyperekplexia
Hyperekplexia may present predominantly as episodes of severe apnoea with high-voltage rhythmic 8-30 CMAP (compound muscle action potential) superimposed on ictal EEG and ECG traces: if there is auditory startle and head retraction without habituation on tapping the tip of the nose then it is permissible to go straight to analysis of hyperekplexia genes (GLRA1 and GlyT2).
Brainstem malformations
Central hypoventilation (Ondine's curse)
Although apnoea is more likely to occur in sleep with most causes, in congenital hypoventilation it exclusively does so. This disorder of autonomic regulation may be associated with Hirschsprung disease and later neural crest tumours. Polyalanine repeats are found in the paired homeobox gene PHOX2b.
Floppy baby
The clinical distinction should be attempted between non-paralytic hypotonia which tends to be axial hypotonia, and weakness which tends to affect preferentially the head and the limbs.
Ill floppy baby
Investigations will include microbiological tests, CSF examination, brain ultrasound (± MRI), blood ammonia and lactate, plasma and urine amino acids and urine organic acids. Dysmorphism will lead to chromosome analysis as well as determining copper, copper oxidase, very long chain fatty acids (VLCFAs) and sialotransferrin status.
Axial hypotonia without limb weakness
Prader-Willi syndrome
Prader-Willi syndrome would be suggested by the need for tube feeding, cat-like cry, Micky saliva, extreme poverty of movement and a combination of axial hypotonia and limb dystonia. FISH (fluorescent in situ hybridization) testing should be conducted for deletion on chromosome 15ql3 and, if negative, MLPA (multiplex ligation-dependent Probe amplification - see Chapter 2.13).
Peroxisomal Disorders
see Peroxisomal Disorders
Brain malformations
Brain malformations shown on imaging may be associated with metabolic disorders
Generalized weakness
Myasthenia
When maternal myasthenia is present little difficulty arises. In the absence of maternal myasthenia various congenital myasthenic syndromes (CMS) should be considered in any infant with stridor, respiratory (including apnoeic attacks or 'infantile syncope') and feeding difficulties. Eye signs such as ptosis may be minimal or absent and a high index of suspicion of CMS is needed to allow directed investigations.