INTRODUCTION :
Myoclonus-dystonia (M-D) is a hyperkinetic movement disorder defined as a syndrome of sustained involuntary muscle contractions (myoclonus) frequently causing repetitive twisting movements or abnormal postures (dystonia) (Fahn et al., 1998). The myoclonic jerks typical of M-D most often affect the neck, trunk, and upper limbs with less common involvement of the legs. Approximately 50% of affected individuals have additional focal or segmental dystonia, presenting as cervical dystonia and/or writer’scramp (Raymond et al, 2003). M-D is compatible with an active life of normal span. Psychiatric disorders have been reported to be associate with M-D, Obsessive-Compulsive Disorder (OCD), anxiety-related disorder, depression and alcohol dependence. Most affected adults report a dramatic reduction in myoclonus in response to alcohol ingestion. Symptom onset is usually during the two first decades: earlier (<1 year) or later (up to 40 years) (Raymond et al., 2008).
Myoclonus-dystonia is transmitted in an autosomal dominant manner, and may occur sporadically. A  proband with M-D may have inherited the disorder from a parent (50% chance of inheriting the pathogenic variant) or have it as the result of a de novo pathogenic variant. The SGCE gene is imprinted, with incomplete penetrance, which is dependent on the parental origin, and occurs only when mutations affect the paternal copy of this gene. Thus, almost all children who inherit an SGCE  pathogenic variant from their father develop symptoms, however close to 95% of children who inherit an SGCE  pathogenic variant from their mother do not (Grabowski et al.,2002; Müller et al, 2002; Raymond et al., 2008). There are several other human genes that are imprinted, including genes located on chromosome 7, and many of them are involved in human diseases. Usually, the mechanism of imprinting is a methylation of cytosine residues at the promoter region that inactivates the gene. This mechanism has been confirmed for the SGCE gene by showing a differential pattern of methylation of the parental allele in patients with M-D (Grabowski et al., 2002). In some of these patients a loss of imprinting with subsequent biallelic expression of the SGCE gene has been demonstrated (Müller et al., 2002).
The primary M-D locus identification has been done in a large North American family in 1999 and was mapped on chromosome 7q21.3 (Nygaard et al., 1999) and confirmed in other families (Klein et al., 2000; Asmus et al., 2001; Vidailhet et al., 2001). The SGCE gene consists of 13 exons (exon 1–11, 11b, 12) and encodes for a 438-amino acid protein with a single transmembrane domain. The SGCE is a member of a gene family that also includes α, β, δ, ε, and ξ sarcoglycans that constitute an essential structure of dystrophin-associated glycoprotein complex in striated muscle.
Mutations in the ε-sarcoglycan gene (SGCE , DYT11 locus, MIM 604149) represent the major genetic cause, but not the only one, other loci are associated with the disease like DYT15 locus on chromosome 18p11 and in a proportion of patients no genetic alteration is found (Grimes et al., 2002). Various mutations (>100) in theSGCE gene have been found to cause M-D, including nonsense, missense, deletions and insertions (Asmus et al., 2001). Most of these mutations lead to an abnormally short, non functional ε-sarcoglycan protein that is quickly broken down (Esapa et al., 2007; Misbahuddin et al, 2007). Other mutations prevent the protein from reaching the cell membrane where it is needed. This lack of functional protein seems to affect the regions of the brain involved in coordinating and controlling movements and leads to the involuntary movement’s characteristic of myoclonus-dystonia. It is unclear why SGCE gene mutations seem to affect only these areas of the brain (Raymond, 2012).
The epidemiology of M-D is not well established. However, it is known that M-D affects most, if not all, racial groups including Africans, Europeans, Chinese, Indians, and Brazilians (Borge et al, 2007, Chen et al, 2008). In Morocco, few studies have been conducted to exploreSGCE gene mutations responsible of Myoclonus-dystonia (M-D) but a two different heterozygous SGCE mutations (c.769A>C) and c.391-3 T> C) have been reported in a study including 12 patients with a sporadic M-D (Rachad et al, 2019). Here, we report the first observation of a familial form of myoclonic dystonia, the case of a Moroccan 17-year-old girl suffering from myoclonic dystonia, using a new approach for medical genetics counselling in National Reference Laboratory (LNR) based on Whole Exome Sequencing (CentoXome Gold®) diagnostic strategy. Molecular explorations in neurogenetics using WES have a positif impact on the patient and his family’s medical care management, socio-professional adaptation and genetic counselling and helps to the comprehension of the pathogenicity of mutations.