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Early stages of the Rett syndrome and infantile neuronal ceroid lipofuscinosis--a difficult differential diagnosis
1Department of Pediatrics II, University of Gothenburg, Sweden.
Insights
Rett syndrome (RS) and infantile neuronal ceroid lipofuscinosis (INCL) share early symptoms, making diagnosis difficult. Differentiating features emerge later, with biopsies crucial for INCL confirmation.
Area of Science:
- Pediatric Neurology
- Neurodegenerative Diseases
- Genetics
Background:
- Rett syndrome (RS) and infantile neuronal ceroid lipofuscinosis (INCL) exhibit similar early clinical manifestations.
- Distinguishing between these rare neurodevelopmental disorders in infancy is challenging.
- Early diagnosis is critical for appropriate management and genetic counseling.
Purpose of the Study:
- To compare neurodevelopmental, neurological, ophthalmological, neurophysiological, and CT data between girls with RS and children with INCL.
- To identify early clinical clues for differentiating RS and INCL.
- To establish criteria for accurate diagnosis of INCL.
Main Methods:
- Comparative study of ten girls with RS and six children with biopsy-confirmed INCL.
- Analysis of neurodevelopmental, neurological, ophthalmological, neurophysiological, and CT findings.
- Review of electrophysiological (EEG, ERG) and imaging (CT) data.
Main Results:
- Early regression, loss of motor skills, speech, and hand stereotypies were indistinguishable between RS and INCL.
- Early diagnostic clues for INCL included transient drop spells, head control loss, myoclonias, EEG flattening, cortical atrophy on CT, and abnormal ERGs.
- A biopsy with characteristic electron microscopy findings was necessary for definitive INCL diagnosis.
- Clinical differentiation became possible after 2.75-3 years of age, with visual failure and motor decline characteristic of INCL.
Conclusions:
- While early symptoms of RS and INCL are similar, specific clinical signs and diagnostic tests allow for differentiation.
- Early identification of INCL is aided by neurological and ophthalmological findings, alongside characteristic biopsy results.
- Accurate diagnosis, particularly of INCL, requires a multidisciplinary approach including specialized investigations.
Abstract:
The Rett syndrome (RS) and infantile neuronal ceroid lipofuscinosis (INCL) are known clinically to present with quite similar manifestations in the very first stages of disease. Ten girls, born 1982-85, from the Swedish series of RS, were compared with 6 children with biopsy-confirmed INCL, deriving from 4 families, as to neurodevelopmental, neurological, ophthalmological, neurophysiological, and CT data. The rapid regression at 1-2 years of age with loss of acquired fine motor skill, learned words, and communication were found to be inseparable between the diseases, as were the successively developing hand and finger stereotypies. Early clues for differential diagnosis were the appearance of transient drop spells, loss of head control, and irregular myoclonias in INCL, flattening of the EEG, early cortical atrophy indicated at CT, and particularly abnormal ERGs. For accurate diagnosis of INCL a biopsy with characteristic EM findings of "snowball" aggregates is a necessity. After 2 3/4-3 years of age, a clinical differentiation was possible in all cases, with visual failure and rapidly decreasing motor ability, head control deterioration, hyperexcitability, and trunk-limb extension tonus being characteristic for INCL.