2.2 Chromosome aberrations

At 2010 group of genetics from the Department of Pediatrics, University of Michigan (Ann Arbor, Michigan, USA), has found de novo 598 kb 16p11.2 microduplication in a boy with refractory MMPSI, who has developed seizures in 4 months and also has spastic quadriparesis, severe global developmental delay, hypotonia, and microcephaly [21].

In most cases, pattern of the first seizure includes motor component of one limb or half of the body; and 50% of the patients develop secondary generalization. In some cases after seizure onset, their frequency uncontrolled rapidly rises to status epilepticus. However, seizures could have longer duration, but at onset seizures often go unrecognized. Cases with autonomic manifestation (episodes of apnea, short blackouts with cyanosis or redness) are difficult to diagnose [3]. Thus, in observation by Gerard et al. [4], epileptic seizures with diffuse erythema and sweating with subsequent hiccups were reported as gastroesophageal reflux, and only a few weeks later, addition of focal seizures was noted, which made diagnosis obvious [4]. According to observations by Dulac, the initial period of the disease usually lasts from 1 week to 3 months (average – 45 days). During this period,

Malignant Migrating Partial Seizures of Infancy (Coppola-Dulac Syndrome)

DOI: http://dx.doi.org/10.5772/intechopen.82838

In the age of 24 days to 10 months (mean 4.5 months), seizures become very frequent and polymorphic but usually are still focal. Seizures usually get clustered (serial) nature, mental and motor retardation is clear. Clinical manifestation of seizures may include head and eye version, lateralized eyeball twitching, fixed gaze, clonic eyelid twitching, tonic tension or clonic spasms of one limb or hemispasms, axial tonic spasms, chewing or sucking movements, episodes of apnea, flushing, hypersalivation, and secondary generalized seizures. One patient may have multiple different combinations of seizures. Typically, seizure duration is 1–4 minutes, but in some cases, it may persist up to several 1 of minutes, until the status epilepticus development. As far as the disease progresses, secondary generalized seizures became more frequent. Seizures are almost continuous or occur as a series 5–30 times per day, mainly on awakening and when falling asleep. Seizure periods may alternate with clear periods when seizures occur within 2–5 days continuously, and

then there are several "light" days (the cyclic course of disease) [1–3, 26]. It should be considered that many seizures are hardly noticeable visually and often remain unrecognized for parents and medical staff. In particular, these are "volatile" paroxysms, as short episodes of apnea, episodes of eyes closing or eyes deviation, episodes of facial flushing, etc. Only video-EEG monitoring can prove

The course of the disease and the severity of clinical symptoms often have undulating pattern: a period of severe illness and permanent seizures may continue for several weeks, and then it is replaced by a relatively favorable period of the temporary seizure regression and some improvement in cognitive and motor functions. This phenomenon generates additional difficulties in controlling the quality of care as it is quite difficult to differentiate in which case the decrease in frequency and severity of seizures is a true response to therapy and in which case it is subject

Under personal observation of patients with MMPSI, age of seizure onset ranged from the 1st day of postnatal life up to 6 months of life. MMPSI were characterized by marked polymorphism (Table 2) and high frequency of epileptic seizures and were in fact a special form of infantile status epilepticus (SE) in the form of migrating multifocal SE. All patients had five or more types of epileptic seizures. Neurological findings in MMPSI children marked with neurological impairment from birth‑severe central tetraparesis, often with muscular hypotonia in the axial and limb muscles [1], microcephaly, strabismus, and athetoid hyperkinesis [25]‑are common. Many patients in dynamics are unable to walk and sit without support and in severe cases are also unable to control the vertical head position, drink, and swallow. In all cases, there is mental retardation, usually severe, and visual

Personal patients with MMPSI (n = 35) in neurological status had a high repre-

sentation of various disorders: high level of stigmatization was observed in 15

seizures may be quite rare, for example, once a week [3].

the epileptic genesis of paroxysmal phenomena.

to the course of the disease.

agnosia [3].

115

In 2012 Poduri and colleagues from the Department of Neurology of Children's Hospital Boston (Massachusetts, USA) in a patient, born of consanguineous Palestinian parents, with clinical manifestation as MMPSI, identified a homozygous 486 kb deletion on chromosome 20p12.3 encompassing the promoter region and exons 1, 2, and 3 of the PLCB1 gene. The deletion breakpoints were mapped from 8,094,049–8,094,072 to 8,580,261–8,580,284 (GRCh37). The breakpoints lie within two LINE nuclear elements and likely arose from nonallelic homologous recombination. PLCB1 gene (607,120; locus 20p12.3) is responsible for early infantile epileptic encephalopathy type 12 (EIEE12; 613,722). Phospholipase C-beta (PLCB) catalyzes the generation of inositol 1,4,5-trisphosphate (IP3) and diacylglycerol (DAG) from phosphatidylinositol 4,5-bisphosphate (IP2), a key step in the intracellular transduction of many extracellular signals. The PLCB1 gene encodes a mammalian PLCB isoform that is expressed in cerebral cortex, hippocampus, amygdala, lateral septum, and olfactory bulb [22].

### 2.3 Other etiological factors

Most cases of MMPSI are considered as unknown etiology (cryptogenic). But also MMPSI had its symptomatic analogs including cases considered as dual pathology [1–3, 20, 23].

In two of three cases for the first time presented by Coppola et al., neuropathologic brain examination showed marked loss of hippocampal neurons in combination with gliosis in the CA1 sector of hippocampal pyramidal layer [1, 23].

Personal observation of 35 cases with MMPSI contains 12 children with symptomatic clinical-electroencephalographic copies of MMPSI (5 boys and 7 girls). Only two infants had cerebral dysgenesis: lissencephaly-pachygyria in one girl and polymicrogyria in another girl. Other ten children had severe perinatal hypoxicischemic CNS disturbances (four of them mixed with perinatal infections‑cytomegalovirus, ureaplasma, chlamydia, herpes type 1) that caused serious brain damage, tetraparetic spastic form of cerebral palsy, and severe retardation in combination with epileptic encephalopathy. Their clinical and video-EEG signs demonstrated MMPSI picture.
