Expanding gray zones in ERCC2 mutations; a patient with XP phenotype and acute post-infectious leukodystrophy

Mutations in ERCC2, a Nucleotide Excision Repair (NER) gene leads to Xeroderma pigmentosum (XP), Trichothiodystrophy (TTD) and Cockayne Syndrome (CS) phenotypes with various severities. While patients undergo XP disease are primarily suffering from skin hypersensitivity but rarely having central nervous system problems, TTD and CS patients are mostly having neurological disorders. In addition to that severe changes in hair and nail texture are especially unique to TTD. Hereby we report a previously healthy patient developed a rapid neurological decline and severe leukodystrophy due to an acute infection in which kept up with mild UV sensitivity and mild developmental delay. Pathophysiology of infection related neurodegeneration and DNA repair genes are also discussed

Lunapark deficiency leads to an autosomal recessive neurodevelopmental phenotype with a degenerative course, epilepsy and distinct brain anomalies

LNPK encodes a conserved membrane protein that stabilizes the junctions of the tubular endoplasmic reticulum network playing crucial roles in diverse biological functions. Recently, homozygous variants in LNPK were shown to cause a neurodevelopmental disorder (OMIM#618090) in four patients displaying developmental delay, epilepsy and nonspecific brain malformations including corpus callosum hypoplasia and variable impairment of cerebellum. We sought to delineate the molecular and phenotypic spectrum of LNPK-related disorder. Exome or genome sequencing was carried out in 11 families. Thorough clinical and neuroradiological evaluation was performed for all the affected individuals, including review of previously reported patients. We identified 12 distinct homozygous loss-of-function variants in 16 individuals presenting with moderate to profound developmental delay, cognitive impairment, regression, refractory epilepsy and a recognizable neuroimaging pattern consisting of corpus callosum hypoplasia and signal alterations of the forceps minor ('ear-of-the-lynx' sign), variably associated with substantia nigra signal alterations, mild brain atrophy, short midbrain and cerebellar hypoplasia/atrophy. In summary, we define the core phenotype of LNPK-related disorder and expand the list of neurological disorders presenting with the 'ear-of-the-lynx' sign suggesting a possible common underlying mechanism related to endoplasmic reticulum-phagy dysfunction

ASSOCIATION BETWEEN MIGRAINE AND ALLERGIC RHINITIS IN CHILDHOOD AND ADOLESCENCE

Objective: Migraine and allergic rhinitis (AR) represent common childhood and adolescent conditions. The aim of this study to assess AR prevalence, treatment outcome, and clinical issues in childhood and adolescence migraine patients

Endocrinological Evaluations of a Neurofibromatosis Type 1 Cohort: Is it Necessary to Evaluate Autoimmune Thyroiditis in Neurofibromatosis Type 1?

Background: Neurofibromatosis type 1 is an autosomal dominant neurocutaneous disorder in which the coexistence of autoimmune thyroiditis and thyroid gland tumours has been reported previously. Aims: To determine the thyroid function and autoimmune thyroid diseases in neurofibromatosis type 1 patients in order to identify the possible association between neurofibromatosis type 1 and thyroid diseases. Study Design: Case-control study. Methods: The study includes 78 consecutive patients diagnosed with neurofibromatosis type 1 between June 2010 and June 2014 and 50 healthy controls. Baseline demographic data were generated from patient examination record forms, including age, sex, height, and weight, as well as levels of free triiodothyronine, free thyroxine, thyroid-stimulating hormone, anti-thyroid peroxidase and anti-thyroglobulin levels. Results: Mean age, sex, and body mass index were similar in both groups (p>0.05). The mean levels of free triiodothyronine, free thyroxine, and thyroid-stimulating hormone were not statistically different between the neurofibromatosis type 1 and control groups. Similarly, no statistically significant difference was observed between the neurofibromatosis type 1 and control groups for anti-thyroid peroxidase and anti-thyroglobulin positivity (2.5% vs 0%, p>0.05). Conclusion: Screening for autoimmune thyroid disease and thyroid function seems to be unnecessary in patients with neurofibromatosis type 1

Evaluation of the parents’ anxiety levels before and after the diagnosis of their child with a rare genetic disease: The necessity of psychological support

Background: The diagnosis of the rare genetic diseases has great importance in treating multisystemic conditions, preventing potential complications, and estimating disease risk for family members. The duration of obtaining genetic test results is varies. The demand to learn the diagnosis of a possible untreatable illness involves a struggle between uncertainty and a lifetime chronic disease. The current uncertainty of their child's condition and the long wait for a diagnosis may increase the parents' anxiety level and cause difficulties in the continuation of diagnostic procedures in some families. This study aimed to investigate the prediagnosis and postdiagnosis anxiety levels of parents who have a child with a rare genetic disease. Method: The parents in this study, mothers or fathers, admitted their children to the Bezmialem Vakıf University Medical Genetics Clinic due to a suspected rare genetic disease (n = 40). Researchers created “The Sociodemographic Questionnaire” and used it to analyze the parents' sociodemographic status. In addition, they used the State-Trait Anxiety Inventory (STAI) to determine the anxiety levels of the parents. Results: The state anxiety levels of parents decreased significantly after learning the diagnosis. However, there was no statistically significant decrease observed in trait anxiety levels. Conclusion: Data from this study revealed that informing parents about their child's disease and properly explaining to them the expected difficulties might help to reduce their anxiety levels. Psychological support for parents is necessary to reduce their long-term stress, thus increasing the patient's compliance with treatment

Microcephaly and Blepharophimosis in a girl with 46,XX,ins(6;3)(q23;q27q21)

This clinical report describes a one year old girl with severe microcephaly,moderate developmental delay and blepharoimosis. She had no internalorgan malformations and structural brain abnormalities. Frequent upperrespiratory infections were noted. The chromosome analysis revealed46,XX,ins(6;3)(q23;q27q21) de novo. 44k array was also performed andshowed no abnormalities.The Blepharophimosis phenotype is known to be associated with the FOXL2gene which is located at 3q22.3. The ATR gene that is responsible for theSeckel Syndrome phenotype is located at 3q23. We are awaiting targetedarray analysis results, which will show us the etiology of overlapping microcephalyand blepharophimosis phenotypes