DEVELOPMENTAL REGRESSION H
History
Theo is a 7-month-old boy who is seen as an urgent referral in the paediatric clinic. His parents have been concerned that he has stopped interacting with them as he used to, and that he has started to have unusual repetitive movements. He was born at term by elective Caesarean section, and he had no problems in the neonatal period. His parents are not consanguineous. He smiled at 5 weeks of age and by about 4 months he could support his head well when held in a sitting position, was making lots of sounds, was interested in everything around him and was reaching to touch objects. Over the last month, he has almost stopped vocalizing, seems much less interested in his surroundings and no longer seems to be as able to support his head. About 3 weeks ago he started having clusters of jerking movements, which his parents initially thought were ‘startle responses’. The movements are symmetrical and cause his arms to move in front of his body and his neck to flex.
Examination
Theo is well grown for his age, with a weight of 9 kg (75th centile), length 72 cm (75th centile) and head circumference 45 cm (50th centile). Cardiovascular, respiratory and abdominal examinations are unremarkable. Cranial and peripheral nervous system examination is normal. There are five patches of pale pigmentation on the skin of his abdomen. He is able to fix on a light source and will follow it briefly but he shows little interest in faces or interacting with toys. When placed in a sitting position, his head drops forward after a few seconds, and when placed prone he does not lift his head from the ground. He does not smile or vocalize during the consultation.
Questions
• What are the most worrying features of this history and what diagnosis do you suspect?
• What investigations should be performed in the first instance?
• What underlying diagnosis may be present?
Medicine
It is clear from the history that there has been developmental regression – loss of previously attained developmental milestones. The abnormal movements are suggestive of infantile spasms, a seizure type causing contraction of axial muscles, resulting in a spectrum of abnormal movements from a small nod of the head to a full ‘jack-knife spasm’. This combination makes it likely that this child has West syndrome, an epilepsy syndrome characterized by infantile spasms, developmental regression and hypsarrhythmia (a chaotic pattern) on EEG. West syndrome starts in the first year of life and can have a variety of underlying causes, including structural brain abnormalities, neurometabolic disease, neurocutaneous syndromes and acquired brain injury. The seizures are difficult to control with medication, and the developmental outlook is poor. This is not necessarily the case with all causes of developmental regression, and it is very important to try to identify any treatable underlying disease, as this may dramatically change the neurodevelopmental outlook.
Causes of developmental regression
Examples
Acquired brain injury Hypoxia, meningitis
Seizure disorders West syndrome, Landau–Kleffner syndrome
Neurometabolic/neurodegenerative Mitochondrial disorders, Tay–Sachs disease
Toxic substances Heavy metal poisoning, e.g. lead
Infectious Subacute sclerosing panencephalitis, prion disease
Pervasive developmental disorder Autism, childhood disintegrative disorder, Rett’s syndrome
In the first instance, this child will require an EEG to look for hypsarrhythmia and an MRI scan to look for structural brain abnormalities. Blood tests should include a full blood count, renal and liver function tests, calcium, phosphate, glucose, lactate, ammonia and amino acids. Urine should be sent for urine amino and organic acids. Examination with a Wood’s (ultraviolet) light will help to determine if there are hypopigmented areas of skin, which may be difficult to see in normal light and could indicate an underlying neurocutaneous syndrome. Further investigations should be directed by a paediatrician with experience in neurology and epilepsy. The presence of depigmented patches on the skin (possibly ash leaf macules) raises the possibility of tuberous sclerosis. Seizures are a common presenting feature and indicate the presence of hamartomas in the central nervous system. This neurocutaneous syndrome is autosomal dominantly inherited, although many cases are new mutations. Clinical features are due to hamartomas which occur in multiple organs, including brain, skin, eyes, kidneys and heart. Tuberous sclerosis arises from defects in either of the two genes encoding the interacting proteins (tuberin on chromosome 16, and hamartin on chromosome 9) involved in the regulation of cellular growth and differentiation. The other two most common neurocutaneous syndromes are neurofibromatosis and Sturge– Weber syndrome.
KEY POINTS
• Developmental regression requires prompt and thorough evaluation by a specialist.
• Infantile spasms are usually associated with diseases with a poor prognosis. • Tuberous sclerosis is one of the commonest causes of developmental regression and infantile spasms.
need an explanation for this answer? contact us directly to get an explanation for this answer