Introduction
Congenital muscular dystrophies (CMDs) represent a heterogeneous group of early-onset muscle disorders presenting primarily with hypotonia and delayed motor development. Several genes ...are known to be responsible for CMDs, including the
LAMA2
gene, involved in merosin-deficient type 1A (MDC1A), and the
FKRP
gene involved in muscular dystrophy-dystroglycanopathy type B5 (MDDGB5). These two forms of CMD are autosomal recessive and are each characterized by the presence of a mutation with a founder effect in South Tunisia. Cognitive development associated with the founder mutation in the
LAMA2
gene (c.8007delT) is often conserved, whereas in the founder mutation of the
FKRP
gene (c.1364 C>A), motor impairment is associated with intellectual disability (ID).
Objectives
To compare the psychological impact of motor impairment in children presenting these two forms of CMD and their families.
Methods
The study consisted of a survey of parents of children with a confirmed diagnosis of MDC1A (5 from 3 unrelated families) or MDDGB5 (3 from 3 unrelated families). The correspondent founder mutation was already identified in the homozygous state by targeted sequencing. Participants’ parents completed the Parent Strengths and Difficulties Questionnaire (SDQ), a behavioral screening tool designed for children aged from 2 to 17 years. The SDQ assesses emotional symptoms, behavior problems, hyperactivity, and peer relationships; The SDQ Impact Supplement assesses the impact of all these children’s difficulties on their families.
Results
The average age of the children was 4.95±3.92 with two children who were not assessable by the SDQ (age< 2 years). Unlike children with MDC1A, ID has been reported in all children with MDDGB5. The mean SDQ total score for children with MDC1A was 11, whereas the mean score for children with MDDGB5 was 14.875, reflecting greater difficulty for children with MDDGB5. The family impact score was higher in families with children with MDDGB5 than in children with MDC1A (10,5 vs 7), which may be due to the burden of management of the ID associated with the motor impairment. The more pronounced difficulties associated with MDDGB5 are likely to be related to the associated ID. Whereas in MDC1A, the difficulties observed are related to the direct impact of the motor impairment. The presence of cognitive disorders associated with a motor deficit aggravates behavioral adaptation and makes the management of these children more difficult.
Conclusions
In the absence of a comparable study in the literature, the present is conducting future studies on the behavioral profile of children with CMD to obtain a better understanding of their difficulties in everyday life and to develop interventions adapted to their families
Disclosure of Interest
None Declared
Introduction
Autism Spectrum Disorder (ASD) is a multifactorial neurodevelopmental disorder, with both contribution of genetic and non-genetic factors. A collaboration of
de novo
mutations and ...prenatal with postnatal environmental factors are likely to play a role. ASD can be syndromic or non-syndromic. The etiology of non-syndromic ASD is still relatively undefined due to its genetic heterogeneity. Contrary to non-syndromic ASD, syndromic ASD is often associated with chromosomal abnormalities or monogenic alterations. Familial cases of ASD support the strong genetic component of ASD.
Objectives
To collect clinical arguments supporting a genetic cause of autism spectrum disorder.
Methods
We present a clinical study of familial cases of ASD. The families were recruited as part of a collaborative project between the department of Medical Genetic and the department of Child Psychiatry in Hedi Chaker Hospital, Sfax, Tunisia. The clinical and paraclinical data were collected retrospectively.
Results
Our study included 11 unrelated families from southern Tunisia, each with two ASD children, among them four couples of twins. Most families (80%) are consanguineous belonging to a middle socioeconomic class. None of the parents suffered from psychiatric disorder and a familial history of autism was reported in one family. Perinatal history, including advanced maternal or paternal age, fetal suffering and/or gestational problems, was found in 35% of cases.
The average age was 9.89 ± 3.787 (3 to 17 years) with a balanced sex-ratio.
ASD was syndromic in seven out of 11 families: facial dysmorphism in half of cases (6/11 families) and/or another comorbidity in 25% of cases (celiac disease, congenital heart disease or idiopathic hydrocephaly). ASD was associated with other(s) neurodevelopmental disorder(s) in all children. Most of cases (14/22) had delayed psychomotor development and all of them had intellectual disability with various degrees. Epilepsy was identified in three cases belonging to unrelated families. Other behavioral problem was identified in 65% of cases.
When the autism spectrum disorder is syndromic and/or associated with other(s) neurodevelopmental(s) disorder(s), this points more towards a genetic origin.
Conclusions
Our study highlights the interest of clinical investigations to determine genetic risk factors of ASD. The identification of a genetic cause in familial cases would contribute not only to better understand the pathological processes of ASD but also to provide an appropriate genetic counseling.
Disclosure of Interest
None Declared
Introduction
Pyridoxine-dependent epilepsy (PDE) is a rare autosomal recessive disease usually associated with neonatal seizures that are sensitive to pyridoxine (vitamin B6). This disease can have a ...significant impact on family functioning, with significant psychological distress in parents. Post-traumatic stress disorder (PTSD), depression, and anxiety are the most common psychiatric outcomes in parents of children with PDE.
Objectives
To investigate the prevalence of significant symptoms of depression, anxiety, and stress in parents of children with PDE.
Methods
The study consisted of a survey of parents accompanying their children diagnosed with PDE. The diagnosis was already confirmed by objectifying a homozygous or a compound heterozygous mutation in the
ALDH7A1
gene in all siblings with heterozygous carrier parents. The Impact of Event Scale-Revised (IES-R) was used to assess parental post-traumatic stress, and the Hospital Anxiety and Depression Scale was used to screen for parental depression and anxiety.
Results
Our study included eight unrelated families with one infant presenting a confirmed PDE disease. The average age of the children with epilepsy was 4.18 years (8 months to 12 years) with equal representation of both sexes.
Half of parents surveyed had depressive symptoms and about two thirds reported anxious symptomatology. These troubles are mainly related to the uncertain prognosis of the disease, even with vitamin B6 supplementation, and the high risk of recurrence in siblings, which led some parents to not have other children. A higher anxiety scores was reported in parents who claimed to have difficulties in providing the necessary vitamin supplements to their affected children on a regular basis. PTSD was diagnosed in three parents: most parents reported difficulties in dealing with stress, specifically in relation to the unpredictability of seizures and the unavailability of medical care for their child, which taxed their financial resources and made it difficult for them to perform their roles effectively.
Besides, being an autosomal recessive transmission disease, the notion of responsibility/guilt was not reported by either parent, and both parents are equally involved in the care of their child.
Conclusions
A significant proportion of children’s parents with pyridoxine-dependent epilepsy are suffering from depression, anxiety, and post-traumatic stress. A deeper understanding of the clinical expressions of these troubles could help practitioners to develop prevention and intervention strategies for these parents.
Disclosure of Interest
None Declared
IntroductionCornelia De Lange syndrome (CdLS) is a dominant and rare genetically heterogeneous syndrome. It is characterized by a large phenotypical spectrum going from a classical to a non-classical ...form affecting multiple organ systems including central nervous, locomotor, skin, gastrointestinal, immune and endocrine systems in association with specific dysmorphic features. Neuropsychiatric manifestations represent a hallmark of CdLS phenotype.ObjectivesThe aim of this study is to describe the neuropsychiatric features of Cornelia De Lange syndrome.MethodsThis is a descriptive and retrospective study compromising unrelated Tunisian patients diagnosed clinically and genetically with CdLS during the period between 2002-2021. Each patient underwent a comprehensive clinical evaluation. In this study, we focused on neuropsychiatric and behavioural phenotype specifying intellectual disability(ID), language delay (LD), autism spectrum disorder (ASD), hyperactivity, aggressivity, specific learning disorder(SLD), sleep problems, compulsive behaviours and social anxiety disorders during adolescence.ResultsA total of nine patients were included in this study. ID was present in all the evaluated patients with different level of severity evolving from mild (8/9) to severe (1/9). LD in absent of hearing problems was detected in two patients. Hyperactivity was found in three patients. Aggressivity was discovered in one patient in a form of self-injurious behaviour in one patient and hetero-aggressivity in another. None of our patients was diagnosed with ASD. Sleep problems such as frequent night-time awakenings were observed in one patient. All patients at age of schooling presented different levels of SLD. None of our patients was diagnosed with anxiety or compulsive behaviours.ConclusionsOur results support the implication of behavioural and psychiatric features in CdLS phenotype. All of symptoms described in the literature were present in our patients. Further evaluation of our patients during their life is important to reveal age-related features such as anxiety or compulsive behaviours. These features can be used to inform specific psychiatric assistance for family psychoeducation, psycho-social interventions, and cognitive-behavioural education treatment approaches in individuals with CdLS.Disclosure of InterestNone Declared
Le Lepréchaunisme ou syndrome de Donohue est une maladie congénitale d’insulinorésistance sévère caractérisée par un retard de croissance intra-utérin (RCIU) et postnatal, une dysmorphie ...caractéristique et des perturbations métaboliques (hyperinsulinisme, hyperandrogénisme). Elle est due à des mutations bi-alléliques du gène INSR codant le récepteur de l’insuline. Le but de ce travail était d’étudier les caractéristiques cliniques et génétiques du lepréchaunisme chez une série de patients tunisiens. Nous avons mené une étude rétrospective chez 13 patients adressés au service de génétique de Sfax pour suspicion de Lepréchaunisme. Il s’agit de 13 familles différentes dont 7 sont consanguines. Le sexe ratio est égale à 1. L’âge moyen de diagnostic était de 12jours. La dysmorphie faciale évocatrice et le RCIU sont les motifs les plus fréquents (11/13 patients) associé à une hypo et/ou hyperglycémie chez 9 patients. Hirsutisme a été décrit chez 3 cas et l’hypertrophie de clitoris chez 2 filles. Biologiquement, un hyperinsulinisme a été objectivé chez 3 patients. La recherche ciblée de la mutation trouvée en Tunisie 1, c.3002-3012delinsGGAAG, était positive uniquement chez 2 patients. Pour les autres, le séquençage de tout le gène est en cours. La mutation c.3002-3012delinsGGAAG, située au niveau de l’exon 16 qui code le domaine juxta-membranaire de la protéine, perturbe la structure secondaire de l’ADN et de l’ARN du gène INSR, ainsi que la structure primaire et secondaire du récepteur de l’insuline 1.
Le syndrome de Klinefelter est une anomalie chromosomique présentant une grande variabilité d’expression clinique. Le caryotype sanguin montre une formule chromosomique à 47, XXY homogène dans 80 % ...des cas ou en mosaïque dans 10 % des cas. Rarement, on peut trouver les formules suivantes 48, XXXY, 49, XXXXY, 48, XXYY entrant dans le cadre de variants du syndrome de Klinefelter.
Dans cette étude nous rapportons les caractéristiques cliniques et cytogénétiques de 4 patients présentant les variants du syndrome de Klinefelter. P1, âgé de 6 mois, a été adressé à notre consultation pour dysmorphie faciale avec hypotonie néonatale. Les organes génitaux externes (OGE) sont de type masculin avec testicules en place et présence d’un phémosis. P2, âgé de 14 mois, présente une dysmorphie faciale et un retard psychomoteur. L’examen des OGE montre une ectopie testiculaire gauche. P3 est un nourrisson de 6 mois ayant une dysgénésie gonadique. P4 est un homme âgé de 33 ans qui consulte pour infertilité. Le caryotype standard réalisé pour P1, P2, P3 et P4 montre respectivement les formules chromosomiques suivantes : (48, XXYY), (49, XXXXY), (49, XXXXY/46, XY), (47, XXY29/48, XXYY1).
Les manifestations du syndrome de Klinefelter apparaissent essentiellement à la puberté avec notion de gynécomastie et de petite taille testiculaire, voir même à l’âge adulte avec infertilité. Cependant les variants de ce syndrome ont un spectre phénotypique plus large avec un pronostic plus sévère. La confirmation précoce du diagnostic est essentielle pour la prise en charge thérapeutique et le conseil génétique.
Les chromosomes isodicentriques (idci) représentent l’anomalie de structure la plus fréquente de l’Y décrite dans l’infertilité masculine. Le spectre clinique de cette anomalie cytogénétique est ...assez large allant des mâles quasi normaux ou infertiles aux femelles porteuses ou non de stigmates turnériens en passant par diverses étapes intermédiaires de dysgénésie gonadique et d’ambiguïté sexuelle. Dans ce travail, nous rapportons le cas d’un idci (Yp) chez un homme présentant une azoospermie associée à une petite taille. Une étude de 100 noyaux interphasiques par FISH en utilisant des sondes centromériques des chromosomes X et Y a montré l’état mosaïque de cette anomalie avec la présence d’une lignée cellulaire 45X à 15 %. L’étude des marqueurs STS nous a permis de cerner le point de cassure dans la région Yq11,21–Yq11,22. Cette anomalie chromosomique est responsable d’une duplication de tout bras court du chromosome Y avec délétion totale des régions AZFb,c expliquant l’azoospermie que présente notre patient. Pour sa petite taille, la lignée cellulaire à 45X pourrait l’expliquer par une haplo-insuffisance du gène SHOX. Cependant, nous envisageons de compléter par un bilan étiologique standard afin d’éliminer une autre cause associée. À travers cette étude, nous soulignons l’importance d’une caractérisation moléculaire et cytogénétique précise des anomalies de structure de l’Y observées en cas d’infertilité masculine. Cette caractérisation précise permettra de délivrer un conseil génétique adéquat pour ces patients et d’évaluer leurs espoirs de paternité ainsi que les chances pour réussir une procréation médicale assistée.
Solid pseudopapillary tumor (SPT) of the pancreas is a rare exocrine pancreatic tumor behaving in a low-grade fashion, with limited local invasion risk and a rare metastatic evolution. We report SPT ...in two young females, revealed by abdominal pain and an epigastric mass. The diagnosis of a cystic tumor was based on abdominal ultrasound and CT data in the first case and on MRI in the second. A distal pancreatectomy and splenectomy were successfully performed in the first case and a central pancreatectomy in the second. Histological study confirmed the diagnosis of SPT of the pancreas.
La tumeur pseudopapillaire et solide du pancréas (TPPSP) est caractérisée par un potentiel malin, atténué avec un risque d’extension locale faible et d’évolution métastatique rare. Nous rapportons ...deux observations de TPPSP, chez une adolescente et une jeune femme, révélées par une douleur abdominale et une masse épigastrique. Le diagnostic de tumeur kystique a été porté sur l’échographie et le scanner dans le premier cas et l’imagerie par résonance magnétique dans le second. Le traitement chirurgical a consisté à une splénopancréatectomie gauche dans un cas et une pancréatectomie centrale dans l’autre cas. L’étude histologique confirma le diagnostic de TPPSP.
Solid pseudopapillary tumor (SPT) of the pancreas is a rare exocrine pancreatic tumor behaving in a low-grade fashion, with limited local invasion risk and a rare metastatic evolution. We report SPT in two young females, revealed by abdominal pain and an epigastric mass. The diagnosis of a cystic tumor was based on abdominal ultrasound and CT data in the first case and on MRI in the second. A distal pancreatectomy and splenectomy were successfully performed in the first case and a central pancreatectomy in the second. Histological study confirmed the diagnosis of SPT of the pancreas.
