Patterns of neurological manifestations in Woodhouse-Sakati Syndrome.
Adolescent
Adult
Alopecia
/ complications
Arrhythmias, Cardiac
/ complications
Basal Ganglia Diseases
/ complications
Diabetes Mellitus
Disease Progression
Female
Humans
Hypogonadism
/ complications
Intellectual Disability
/ complications
Male
Middle Aged
Nervous System Diseases
/ genetics
Phenotype
Retrospective Studies
Young Adult
Dystonia
Hypogonadism
NBIA
Woodhouse-Sakati syndrome
Journal
Parkinsonism & related disorders
ISSN: 1873-5126
Titre abrégé: Parkinsonism Relat Disord
Pays: England
ID NLM: 9513583
Informations de publication
Date de publication:
12 2019
12 2019
Historique:
received:
07
05
2019
revised:
23
09
2019
accepted:
07
10
2019
pubmed:
15
11
2019
medline:
2
9
2020
entrez:
15
11
2019
Statut:
ppublish
Résumé
Woodhouse-Sakati syndrome (WSS) is a rare autosomal recessive disease with characteristic neuro-endocrine manifestations. WSS encompasses heterogeneous phenotypes and disease course. We aimed to characterize neurological involvement of the disease through subgrouping of core neurological manifestations. A single-institution retrospective analysis of patients with clinically and genetically confirmed diagnosis of WSS. A total of 38 individuals belonging to 17 families were identified to have WSS. The mean age at enrollment was 30.1 years (range 16-53 years). Neurological involvement was noted in 31 patients (81.5%). Dystonia was the most common neurological manifestation (67%), followed by intellectual disability (45%) and sensorineural hearing loss (30%). Based on the Neurological Impairment Scale (NIS), the disease was recognized to have two distinct patterns. A disabling, rapidly progressive pattern (NIS of 3-4; Type 1) was noted in eighteen patients (12 males, 6 females; 47.4%) with severe disability that occurs within a mean duration of 7.4 ± 3.6 years. Type 2 WSS was identified in twenty patients (8 males, 12 females; 52.6%), and showed either absent or mild neurological involvement with preserved activities of daily living (NIS of 0-1). The mean age of onset for neurological manifestations was earlier in type 1 (12.6 ± 4.5 years) compared to type 2 (18.1 ± 4.3 years). Type 1 WSS has a significantly higher rate of intellectual disability (p= <0.001). In this pleiotropic syndrome, we identified two distinct phenotypes with variable prognosis. A high Interfamilial and intrafamilial phenotypic variability despite having a similar gene mutation suggests a possible role of genetic or environmental modifying factor.
Sections du résumé
BACKGROUND
Woodhouse-Sakati syndrome (WSS) is a rare autosomal recessive disease with characteristic neuro-endocrine manifestations. WSS encompasses heterogeneous phenotypes and disease course.
OBJECTIVE
We aimed to characterize neurological involvement of the disease through subgrouping of core neurological manifestations.
METHODS
A single-institution retrospective analysis of patients with clinically and genetically confirmed diagnosis of WSS.
RESULTS
A total of 38 individuals belonging to 17 families were identified to have WSS. The mean age at enrollment was 30.1 years (range 16-53 years). Neurological involvement was noted in 31 patients (81.5%). Dystonia was the most common neurological manifestation (67%), followed by intellectual disability (45%) and sensorineural hearing loss (30%). Based on the Neurological Impairment Scale (NIS), the disease was recognized to have two distinct patterns. A disabling, rapidly progressive pattern (NIS of 3-4; Type 1) was noted in eighteen patients (12 males, 6 females; 47.4%) with severe disability that occurs within a mean duration of 7.4 ± 3.6 years. Type 2 WSS was identified in twenty patients (8 males, 12 females; 52.6%), and showed either absent or mild neurological involvement with preserved activities of daily living (NIS of 0-1). The mean age of onset for neurological manifestations was earlier in type 1 (12.6 ± 4.5 years) compared to type 2 (18.1 ± 4.3 years). Type 1 WSS has a significantly higher rate of intellectual disability (p= <0.001).
CONCLUSIONS
In this pleiotropic syndrome, we identified two distinct phenotypes with variable prognosis. A high Interfamilial and intrafamilial phenotypic variability despite having a similar gene mutation suggests a possible role of genetic or environmental modifying factor.
Identifiants
pubmed: 31726291
pii: S1353-8020(19)30434-1
doi: 10.1016/j.parkreldis.2019.10.007
pii:
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
99-103Informations de copyright
Copyright © 2019 Elsevier Ltd. All rights reserved.