Diagnostic and severity scores for Cockayne syndrome.

BACKGROUND: Cockayne syndrome is a progressive multisystem genetic disorder linked to defective DNA repair and transcription. This rare condition encompasses a very wide spectrum of clinical severity levels ranging from severe prenatal onset to mild adult-onset subtypes. The rarity, complexity and variability of the disease make early diagnosis and severity assessment difficult. Based on similar approaches in other neurodegenerative disorders, we propose to validate diagnostic and severity scores for Cockayne syndrome. METHODS: Clinical, imaging and genetic data were retrospectively collected from 69 molecularly confirmed CS patients. A clinical diagnostic score and a clinical-radiological diagnostic score for CS were built using a multivariable logistic regression model with a stepwise variable selection procedure. A severity score for CS was designed on five items (head circumference, growth failure, neurosensorial signs, motor autonomy, communication skills) and validated by comparison with classical predefined severity subtypes of CS. RESULTS: Short stature, enophtalmos, hearing loss, cataracts, cutaneous photosensitivity, frequent dental caries, enamel hypoplasia, morphological abnormalities of the teeth, areflexia and spasticity were included in the clinical diagnostic score as being the most statistically relevant criteria. Appropriate weights and thresholds were assigned to obtain optimal sensitivity and specificity (95.7% and 86.4% respectively). The severity score was shown to be able to quantitatively differentiate classical predefined subtypes of CS and confirmed the continuous distribution of the clinical presentations in CS. Longitudinal follow-up of the severity score was able to reflect the natural course of the disease. CONCLUSION: The diagnostic and severity scores for CS will facilitate early diagnosis and longitudinal evaluation of future therapeutic interventions. Prospective studies will be needed to confirm these findings.

Chronic Diarrhea in L-Amino Acid Decarboxylase (AADC) Deficiency: A Prominent Clinical Finding Among a Series of Ten French Patients.

Aromatic L-amino acid decarboxylase (AADC) deficiency is an autosomal recessive inborn error of metabolism, affecting catecholamines and serotonin biosynthesis. Cardinal signs consist in psychomotor delay, hypotonia, oculogyric crises, dystonia, and extraneurological symptoms. PATIENTS AND METHODS: We present a retrospective descriptive multicentric study concerning ten French children with a biochemical and molecular confirmed diagnosis of AADC deficiency. RESULTS: Clinical presentation of most of our patients was consistent with the previous descriptions from the literature (hypotonia (nine children), autonomic signs (nine children), sleep disorders (eight children), oculogyric crises (eight children), motor disorders like hypertonia and involuntary movements (seven children)). We described however some phenotypic particularities. Two patients exhibited normal intellectual abilities (patients already described in the literature). We also underlined the importance of digestive symptoms like diarrhea, which occurred in five among the ten patients. We report in particular two children with chronic diarrhea, complicated by severe failure to thrive. Vanillactic acid (VLA) elevation in urines of one of these two patients led to suspect the diagnosis of AADC deficiency, as in two other patients from our population. CONCLUSION: Some symptoms like chronic diarrhea were atypical and have been poorly described in the literature up to now. Diagnosis of the AADC deficiency is sometimes difficult because of the phenotypic heterogeneity of the disease and VLA elevation in urines should suggest the diagnosis.

[Pseudostatus epilepticus: a severe complication of psychogenic nonepileptic seizures (PNES) in children]. / Pseudostatus epilepticus : une complication grave des crises non épileptiques psychogènes (CNEP) chez l'enfant.

Psychogenic nonepileptic seizures are clinical events that mimic epileptic seizures but are not associated with electroencephalographic discharges. These seizures are seldom reported in children in the literature and could be misinterpreted as generalized tonicoclonic seizures. We report the case of a child, already treated for epilepsy, who presented at 8 years of age with several psychogenic seizures leading to pseudostatus epilepticus. After several hospitalizations, the diagnosis of pseudostatus was established on the basis of clinical semiology, lack of EEG abnormalities during the seizures, and a positive provocation maneuver, which elicited and blocked the manifestations. The clinical spectrum of psychogenic seizures is wide and it is particularly difficult to differentiate psychogenic seizures from epileptic seizures, especially when occurring in children, some of whom are already treated for epilepsy. Well-described clinical features can suggest the diagnosis of psychogenic seizure. It is important and necessary to make the diagnosis as soon as possible in order to rapidly begin appropriate treatment including psychotherapy. In fact, the long-term prognosis in children is better than in the adult population. Associated risk factors, such as anxiety as reported in the present case, have to be sought. Recognizing psychogenic seizures will thus avoid their fixation in the child's personality and the risk of inappropriate and escalating treatments leading to iatrogenic complications.