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J Neurol Neurosurg Psychiatry. 2015 Jul;86(7):782-5. doi: 10.1136/jnnp-2014-309025. Epub 2015 Jan 16.

Severe phenotypic spectrum of biallelic mutations in PRRT2 gene.

Author information

1
Service de Neuropédiatrie, CHU Gui de Chauliac, Montpellier, France.
2
Laboratoire de Génétique, AP-HP, Groupe Hospitalier Lariboisière-Fernand Widal, Paris, France INSERM UMR-S740; Université Paris 7 Denis Diderot, Paris, France.
3
Service de Neurologie Pédiatrique, CHU Timone Enfants, Marseille, France.
4
Service de Neurologie Pédiatrique, CHU Timone Enfants, Marseille, France Aix Marseille Université, INSERM, GMGF UMR_S 910, Marseille, France.
5
AP-HP, Unité d'épilepsie, Institut du Cerveau et de la Moelle épinière, Hôpital Pitié-Salpêtrière, Paris, France INSERM, UMRS 975, et CNRS 7225-Institut du Cerveau et de la Moelle épinière, Hôpital Pitié-Salpêtrière,Université Pierre et Marie Curie-Paris-6, Paris, France.
6
Département des Maladies du Système Nerveux, AP-HP, Hôpital Pitié-Salpêtrière, Paris, France CRICM, INSERM U1127, CNRS UMR 7225, UPMC UMR-S975, Paris, France.
7
Service de Médecine Psychologique Enfants et Adolescents, CHU Saint Eloi, Montpellier, France.
8
Neuropédiatrie HUG, Genève, Suisse.
9
Neuropédiatrie, HFME, Hospices Civils de Lyon, Bron, France Université Lyon 1, F-69008 Lyon, France.
10
INSERM U901, Marseille, France Institut de Neurobiologie de la Méditerranée (INMED), Marseille, France UMR_S901, Université d'Aix-Marseille, Marseille, France.
11
Service de Neurologie Pédiatrique, AP-HP, Hôpital Trousseau, Paris, France.
12
Team Genome and Cancer, Hematology Laboratory Assistance Publique-Hopitaux de Paris, Saint-Louis Hospital, Paris, France Inserm U944, Saint-Louis Hospital, Paris, France.
13
Service de Neuroradiologie, CHU Gui de Chauliac, Montpellier, France.
14
EA 4666, CHU d'Amiens-UPJV, Laboratoire de Génétique, Hôpital Sud, Amiens, France.
15
Service de Neuropédiatrie, CHU Gui de Chauliac, Montpellier, France INSERM U 1051, Institut des Neurosciences de Montpellier, Montpellier, France.

Abstract

BACKGROUND:

Heterozygous dominant mutations of PRRT2 have been associated with various types of paroxysmal neurological manifestations, including benign familial infantile convulsions and paroxysmal kinesigenic dyskinesia. The phenotype associated with biallelic mutations is not well understood as few cases have been reported.

METHODS:

PRRT2 screening was performed by Sanger sequencing and quantitative multiplex PCR of short fluorescent fragments. A CGH array was used to characterise the size of the deletion at the 16p11.2 locus.

RESULTS:

Five patients with homozygous or compound heterozygous deleterious PRRT2 gene mutations are described. These patients differ from those with a single mutation by their overall increased severity: (1) the combination of at least three different forms of paroxysmal neurological disorders within the same patient and persistence of paroxysmal attacks; (2) the occurrence of uncommon prolonged episodes of ataxia; and (3) the association of permanent neurological disorders including learning difficulties in four patients and cerebellar atrophy in 2.

CONCLUSIONS:

Our observations expand the phenotype related to PRRT2 insufficiency, and highlight the complexity of the phenotype associated with biallelic mutations, which represents a severe neurological disease with various paroxysmal disorders and frequent developmental disabilities.

KEYWORDS:

EPILEPSY; MENTAL RETARDATION; MOVEMENT DISORDERS; PAROXYSMAL DISORDER

PMID:
25595153
DOI:
10.1136/jnnp-2014-309025
[Indexed for MEDLINE]

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