Lujan-Fryns syndrome (mental retardation, X-linked, marfanoid habitus)

The Lujan-Fryns syndrome or X-linked mental retardation with marfanoid habitus syndrome is a syndromal X-linked form of mental retardation, affecting predominantly males. The prevalence is not known for the general population. The syndrome is associated with mild to moderate mental retardation, distinct facial dysmorphism (long narrow face, maxillary hypoplasia, small mandible and prominent forehead), tall marfanoid stature and long slender extremities, and behavioural problems. The genetic defect is not known. The diagnosis is based on the presence of the clinical manifestations. Genetic counselling is according to X-linked recessive inheritance. Prenatal testing is not possible. There is no specific treatment for this condition. Patients need special education and psychological follow-up, and attention should be given to diagnose early psychiatric disorders

Human OTULIN haploinsufficiency impairs cell-intrinsic immunity to staphylococcal alpha-toxin

The molecular basis of interindividual clinical variability upon infection with Staphylococcus aureus is unclear. We describe patients with haploinsufficiency for the linear deubiquitinase OTULIN, encoded by a gene on chromosome 5p. Patients suffer from episodes of life-threatening necrosis, typically triggered by S. aureus infection. The disorder is phenocopied in patients with the 5p- (Cri-du-Chat) chromosomal deletion syndrome. OTULIN haploinsufficiency causes an accumulation of linear ubiquitin in dermal fibroblasts, but tumor necrosis factor receptor-mediated nuclear factor kappa B signaling remains intact. Blood leukocyte subsets are unaffected. The OTULIN-dependent accumulation of caveolin-1 in dermal fibroblasts, but not leukocytes, facilitates the cytotoxic damage inflicted by the staphylococcal virulence factor alpha-toxin. Naturally elicited antibodies against alpha-toxin contribute to incomplete clinical penetrance. Human OTULIN haploinsufficiency underlies life-threatening staphylococcal disease by disrupting cell-intrinsic immunity to alpha-toxin in nonleukocytic cells.Peer reviewe

Mesiodens

The presence of an extra supernumerary tooth in the central position of the upper or lower jaw is called mesiodens. These teeth can be present as part of a syndrome or can be found as an isolated finding. Mesiodens is the most frequently found extra tooth, with a prevalence in the general population of 0.15-1.9%, and with a higher frequency in males than females. Usually the shape is conical and mesiodens is smaller than the neighbour incisor. Several hypotheses have been suggested for the formation of supernumerary teeth. Early diagnosis and treatment are needed to support right dental occlusion.status: publishe

A systematic genetic-etiological survey in a Dutch population of institutionalised mentally retarded patients : diagnostic investigations and implications for medical care

Contains fulltext : 19184_systgesui.pdf (publisher's version ) (Open Access)262 p

Deep Phenotyping of Development, Communication and Behaviour in Phelan-McDermid Syndrome

Phelan-McDermid syndrome (PMS; also referred to as 22q13.3 deletion syndrome) is a congenital condition due to a microdeletion in the SHANK3 gene. Cognitive and communicative deficits as well as behaviour in the autism spectrum are often noticed in affected individuals. The aim of the present study was to obtain a detailed phenotype of the development, communication, and behaviour of 15 individuals with PMS by using both quantitative (questionnaires) and qualitative methods (interviews and observations). In addition, data from the patients' medical records were included. In a subgroup of participants (n = 5), data from a previous study were incorporated to enable a comparison over 2 points in time (longitudinal course). Results indicate a severe to profound level of intellectual disability in all participants, impaired adaptive behaviour, a low level of speech and language, a high incidence of features of autism spectrum disorder (ASD), and a high sensory threshold. Younger individuals (age <18 years) exhibited more challenging behaviour and features of ASD. In older individuals with PMS, a regression across many developmental and adaptive domains was frequently reported and observed. We did not find a relation between the deletion size and the severity of the phenotype. Implications of the findings and recommendations for clinical practice and future research are discussed.status: Published onlin

Adolescent met schizofreniformestoornis en terugkerende 16p11.2-duplicatie [Adolescent with a schizophreniform disorder and recurrent 16p11.2 duplication]

Genetische factoren spelen een belangrijke rol in het ontstaan van psychotische stoornissen. Met toenemende evidentie worden verschillende zeldzame copy number variants (cnv’s) geïdentificeerd als risicofactoren. We beschrijven een patiënt die in de adolescentie twee psychotische episodes had. Bij hem werd een 16p11.2-duplicatie vastgesteld, een terugkerende cnv die geassocieerd wordt met verschillende somatische en psychiatrische fenotypes waaronder psychose en schizofrenie. We bespreken de mogelijke klinische relevantie van deze bevinding. Genetic factors play an important role in the development of psychotic disorders. With increasing evidence, several rare copy number variants (cnvs) have been identified as risk factors. We describe a patient who had two psychotic episodes during his adolescence. In this patient, a 16p11.2 duplication was detected. This duplication is a recurrent cnv associated with various somatic and psychiatric phenotypes including psychosis and schizophrenia. The potential clinical relevance of this finding is discussed.status: publishe

Adolescent met schizofreniformestoornis en terugkerende 16p11.2-duplicatie [Adolescent with a schizophreniform disorder and recurrent 16p11.2 duplication]

Genetische factoren spelen een belangrijke rol in het ontstaan van psychotische stoornissen. Met toenemende evidentie worden verschillende zeldzame copy number variants (cnv’s) geïdentificeerd als risicofactoren. We beschrijven een patiënt die in de adolescentie twee psychotische episodes had. Bij hem werd een 16p11.2-duplicatie vastgesteld, een terugkerende cnv die geassocieerd wordt met verschillende somatische en psychiatrische fenotypes waaronder psychose en schizofrenie. We bespreken de mogelijke klinische relevantie van deze bevinding. Genetic factors play an important role in the development of psychotic disorders. With increasing evidence, several rare copy number variants (cnvs) have been identified as risk factors. We describe a patient who had two psychotic episodes during his adolescence. In this patient, a 16p11.2 duplication was detected. This duplication is a recurrent cnv associated with various somatic and psychiatric phenotypes including psychosis and schizophrenia. The potential clinical relevance of this finding is discussed.status: publishe

Consensus recommendations on altered sensory functioning in Phelan-McDermid syndrome

Altered sensory functioning is often observed in individuals with SHANK3 related Phelan-McDermid syndrome (PMS). Compared to typically developing individuals and individuals with an autism spectrum disorder, it has been suggested that there are distinctive features of sensory functioning in PMS. More hyporeactivity symptoms and less hyperreactivity and sensory seeking behaviour are seen, particularly in the auditory domain. Hypersensitivity to touch, possible overheating or turning red easily and reduced pain response are often seen. In this paper the current literature on sensory functioning in PMS is reviewed and recommendations for caregivers, based on consensus within the European PMS consortium, are given

Recent developments in Phelan–McDermid syndrome research: an update on cognitive development, communication and psychiatric disorders

Purpose of review The purpose of this review is to summarize the literature on cognitive development, communication, behavioral or psychiatric aspects and parenting stress in Phelan–McDermid syndrome (PMS) and to discuss the clinical implications and recommendations of these summarized findings. Recent findings PMS is often associated with severe communication impairments, behavioral or psychiatric problems and regression. These challenges may adversely affect and impair the quality of life of the individual with PMS and his family. Summary Individuals with PMS experience intellectual disability, communication and behavioral/psychiatric challenges, such as catatonia, bipolar disorder and regression across the lifespan. Providing appropriate guidance and support to them and their families demands a better understanding of these challenges.status: Published onlin