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At a glance

A rare neurological disease characterized by the occurrence of hypertonia at birth that progressively decreases over the first year of life. However, attacks of hypertonia heightened by the slightest physical stimulus often occur and are responsible for apnea, respiratory depression, severe cyanosis, and death.

Synonyms

Essential Startle Disease; Exaggerated Startle Reaction; Hyperekplexia; Kok Disease; Familial Startle Disease.

History

First described in 1962 by O. Kok and G. W. Bruyn in Leiden, Netherlands.

Genetic inheritance

Autosomal dominant and autosomal recessive with almost complete penetrance.

Pathophysiology

The Stiff Baby Syndrome is caused by heterozygous, homozygous, or compound heterozygous mutation in the GLRA1 gene on chromosome 5q32, which encodes the glycine receptor alpha-1 subunit or mutations of the GLRB gene on 4q32.1, which encodes the beta subunit of the glycine receptor. Other mutations are described on SLC6A5 (11p15.1) of the neuronal presynaptic glycine reuptake transporter GlyT2. The defective receptor causes disruption of the normal inhibitory pathway, descending to the spinal cord to modulate reflexes. The pathophysiology of hypertonia and the exaggerated startle response remains unclear but several hypotheses have been proposed. One hypothesis is that there are hyperactive long-loop reflexes acting as the physiologic basis for the startle disease, suggesting increased cortical neuronal excitability. Electroencephalography is normal, whereas electromyography shows persistent muscle activity (even during sleep); rarely associated with electric quietness. The nerve conduction is normal.

Diagnosis

The diagnosis is a clinical one and is more easily made when other members of the family are affected. The recognition of this entity is important to avoid an erroneous diagnosis of epilepsy and consequent treatment with anticonvulsants. It is also important to distinguish the Stiff Baby Syndrome from other neurological diseases. Electroencephalography (EEG) and electromyography (EMG) are normal while awake and asleep. Low cerebrospinal fluid (CSF) gamma-aminobutyric acid (GABA) level was demonstrated. Responsiveness to diazepam and clonazepam therapy.

Clinical aspects

Onset occurs from birth with hypertonia, hypokinesia, flexed posture, and a peculiar staccato cry. Neonates suffering from the disease are at risk of sudden death from apnea or aspiration if they undergo a prolonged period of rigidity. Later in childhood, individuals may show an exaggerated startle response during waking state with acute generalized hypertonia and loss of voluntary muscle control, resulting in “falling like a log.” The startle can be easily elicited by a loud, unexpected noise or by touching the nose. Marked nocturnal myoclonic jerks are also a characteristic. Intelligence is normal. Inguinal/umbilical hernias and congenital dislocation of hip are common. Symptoms are exacerbated by stress, fatigue, cold, and rainy weather. Infants are at an increased risk of apneas. Medical treatment is with clonazepam. Acute episodes can be terminated using the Vigevano maneuvre which is a forced flexion of the head and ...

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