A rare neurodegenerative disorder with a novel mutation in ROGDI and Rett- like phenotype: Kohlschütter- Tönz syndrome

@#Kohlschütter-Tönz syndrome (KTZS) is a rare neurodegenerative disorder that presents with seizures, developmental delay, psychomotor regression, hypoplastic dental enamel morphology characteristic for amelogenesis imperfecta, and dysmorphologies. Genetic analysis has identified loss of function mutations within the coding region of the ROGDI and SLC13A5 genes in KTZS. In this report, we documented the clinical, radiological, electroencephalographic, and genetic results of a 3.5-year-old Turkish girl, born to nonconsanguineous parents, who was the first patient diagnosed with KTZS in Turkey. The patient presented with Rett syndrome-like phenotype, neurodevelopmental delay, refractory seizures, and amelogenesis imperfecta. After obtaining informed consent, chromosomal DNAwas extracted from the peripheral blood of our patient and her parents. To investigate the moleculardiagnosis of the patient, the clinical exome sequencing was performed. The Sanger sequencing analysiswas performed for all of the family members for the validation and segregation of this mutation. PubMed/Medline, Web of Science, and Google Scholar were also searched to find all of the publisheddata on KTZS. The literature comprises 18 published studies about KTZS. The genetic analysis of ourpatient revealed a novel homozygous c.201-1G>T mutation in the ROGDI gene. The same mutationwas also found to be heterozygous in her mother and father. The mutation caused alternative splicingof the ROGDI translation and resulted in a disruption of the ROGDI protein.

Caracterización de las familias que abandonan el tratamiento de estimulación temprana. Centro Senén Casas Regueiro / Characterization of the families that abandon the early stimulation treatment. Senén Casas Regueiro Center

Introducción: se desconoce por qué las familias y consecuentemente el infante interrumpe o abandona el tratamiento establecido por el Programa de Atención Temprana para los trastornos del neurodesarrollo. Objetivo: Describir las características de las familias que abandonan el tratamiento de estimulación temprana en el centro Senén Casa Regueiro. Material y Métodos: estudio descriptivo, transversal en familias de infantes de 0 a 12 años con trastornos del neurodesarrollo en La Habana Vieja durante el periodo 2014-2015, que considera variables demográficas, sociales y económicas. En el análisis se emplearon las frecuencias absolutas y relativas, la media, la desviación estándar y las pruebas x2. Resultados: la prevalencia de abandono del tratamiento fue del 88,0 por ciento. Los porcentajes de mayor interrupción se presentaron en madres o tutores de 15-18 años (47,20 por ciento, x2 = 10,47 p = 0.0001) y en hijos de padres divorciados (52,00 por ciento). El nivel de escolaridad que mayor porcentaje aportó al problema fue el primario (52,00 por ciento, x2 = 20, 69 p= 0,0000), en familias con mayor número de hijos; de 3-4 hijos (86,40 por ciento, x2 = 29,90 p = 0,00000), que poseían viviendas en malas condiciones (48,00 por ciento x2 = 9,45 p = 0,00021). Los tratamientos más prolongados expresaron mayor porcentaje de abandono (60,00 por ciento, x2 = 3,75 p = 0,053519). Tanto las familias que desertaron del tratamiento, como las que no, presentaron elevados porcentajes de buena satisfacción con el programa (95,20 por ciento y 94,12 por ciento respectivamente). Conclusiones: predominó el abandono al tratamiento en madres cuyos grupos de edades oscilaron entre 15-18 años, divorciadas, en niños con tratamientos más prolongados; destacándose el nivel de escolaridad primario de las madres y las malas condiciones de la vivienda. Asimismo, interrumpieron el tratamiento las familias con mayor número de hijos y menor número de personas con remuneración monetaria(AU)

Introduction: It is unknown why families and consequently, the infant interrupt or abandon the treatment established by the Early Care Program for neurodevelopmental disorders. Objective: To describe the characteristics of families that abandon the early stimulation treatment at the "Senén Casas Regueiro" Center of Comprehensive Pediatric Rehabilitation. Material and Methods: A descriptive, cross-sectional study was conducted in families of infants with neurodevelopmental disorders from 0 to 12 years old in Old Havana, during the period 2014-2015. Demographic, social, and economic variables were considered. Absolute and relative frequencies, the mean, the standard deviation, and the chi-squared tests were used in the analysis. Results: The prevalence of abandonment of treatment was 88.0 percent. The percentages of greatest interruption occurred in mothers or guardians aged 15-18 years (47.20 percent; x2= 10.47; p = 0.0001), and in children of divorced parents (52.00 percent). The level of education that contributed in the highest percentage to the problem was primary schooling (52.00 percent; x2 = 20, 69; p = 0.0000) in families with the largest number of children; families with 3-4 children (86.40 percent; X2 = 29.90; p = 0.00000), who lived in homes in poor conditions (48.00 percent x2 = 9.45; p = 0.00021). Longer treatments expressed a greater percentage of abandonment (60.00 percent; x2 = 3.75; p = 0.053519). Both the families that abandoned the treatment and those that did not do it, showed high percentages of good satisfaction with the program (95.20 percent and 94.12 percent, respectively). Conclusions: Abandonment of treatment predominated in mothers whose age groups ranged between 15-18 years; divorced; in children with more prolonged treatments; highlighting the mothers with primary schooling and poor housing conditions. Likewise, families with a greater number of children and a smaller number of people with monetary remuneration interrupted the treatment(AU)

A Novel c.826G>A Mutation in a Boy with Allan-Herndon-Dudley Syndrome: Clinical Significance of Thyroid Function Tests in Developmental Delay of Unknown Origin / 대한소아신경학회지

Allan-Herndon-Dudley syndrome (AHDS) is an X-linked intellectual disability caused by monocarboxylate transporter 8 (MCT8) deficiency. AHDS manifests in global developmental delay, axial hypotonia, quadriplegia, movement disorders in male patients, and most of them show the delayed or hypomyelination on brain magnetic resonance images. Typically, Triiodothyronine (T3) levels are markedly elevated, thyroid stimulating hormone (TSH) levels are normal or elevated, and free thyroxine (T4) levels are normal or decreased. In AHDS patients, early neurological manifestations are easily mistaken as cerebral palsy with unknown origin. Here, we present a novel c.826G>A mutation in a boy with severe axial hypotonia, limb dystonia and developmental delay. Thyroid function test including TSH, T3, and free T4 levels was the important clue for the diagnosis of AHDS of the patient.

Neurodevelopmental Status of Children Aged 6-30 Months with Congenital Heart Disease.

Background: Children with congenital heart diseases (CHD) are considered to be at high-risk for neurodevelopmental delay, but scant Indian data are available. Objective: To evaluate the neurodevelopmental status of children with CHD. Methods: We enrolled consecutive children aged 6-30 months with echocardiographically-confirmed CHD between June 2013 and January 2014. Children with clinically recognizable genetic syndromes or disorders; visual and/or hearing deficits, and microcephaly; and post-cardiac surgery children were excluded. Development was assessed by Developmental Assessment Scale for Indian Infants (DASII) and Developmental delay defined as Development Quotient (DQ) <70 in either the mental or motor scale. Results: 75 children (53 males) with CHD were enrolled. Acyanotic CHD was seen in 51 children (VSD in 47%), and Tetralogy of Fallot was the commonest cyanotic CHD (25%). Developmental delay was seen in 25% of these children, more in the motor domain (48%) than in mental (12%). Mean motor and mental DQ in acyanotic CHD was 77 and 84, respectively; and 65 and 85, respectively in cyanotic CHD. Mean motor DQ was significantly less than mental DQ in both acyanotic and cyanotic CHD children (P=0.048). Conclusion: Children with CHD are at an increased risk for developmental delay. Periodic surveillance, screening and evaluation should be instituted in them for early identification and appropriate interventions to enhance later academic, behavioral, psycho-social and adaptive function.

Modulating Tone to Promote Motor Development Using a Neurofacilitation of Developmental Reaction (NFDR) Approach in Children with

Objective: To compare the efficacy of a Neurofacilitation of Developmental Reaction (NFDR) approach with that of a Conventional approach in the modulation of tone in children with neurodevelopmental delay. Methods: Experimental control design. A total of 30 spastic children ranging in age from 4 to 7 years with neurodevelopmental delay were included. Baseline evaluations of muscle tone and gross motor functional performance abilities were performed. The children were allocated into two intervention groups of 15 subjects each. In groups A and B, the NFDR and conventional approaches were applied, respectively, for 3 months and were followed by subsequent re-evaluations. Results: Between group analyses were performed using independent t test for tone and primitive reflex intensity and a Mann-Whitney U test for gross motor functional ability. For the within-group analyses, paired t tests were used for tone and primitive reflex intensity, and a Wilcoxon signed-rank test was used for gross motor functional ability. Conclusion: The NFDR approach/technique prepares the muscle to undergo tonal modulation and thereby enhances motor development and improves the motor functional performance abilities of the children with neurodevelopmental delay.

MICrocephaly, disproportionate pontine and cerebellar hypoplasia syndrome: A clinico-radiologic phenotype linked to calcium/calmodulin-dependent serine protein kinase gene mutation.

MICrocephaly, disproportionate pontine and cerebellar hypoplasia (MICPCH) syndrome, a rare X-linked disorder, generally seen in girls, is characterized by neurodevelopmental delay, microcephaly, and disproportionate pontine and cerebellar hypoplasia. It is caused by inactivating calcium/calmodulin-dependent serine protein kinase (CASK) gene mutations. We report a 2-year-old girl with severe neurodevelopmental delay, microcephaly, minimal pontine hypoplasia, cerebellar hypoplasia, and normal looking corpus callosum, with whom the conventional cytogenetic studies turned out to be normal, and an array-comparative genomic hybridization (a-CGH) analysis showed CASK gene duplication at Xp11.4. Our case highlights the importance of using clinico-radiologic phenotype to guide genetic investigation and it also confirms the role of a-CGH analysis in establishing the genetic diagnosis of MICPCH syndrome, when conventional cytogenetic studies are inconclusive.

Multiple Congenital Melanocytic Nevi Associated with Developmental Delay / 대한피부과학회지

Multiple congenital melanocytic nevi (MCMN), defined as the distribution of more than three small- or medium- sized congenital melanocytic nevi (CMN) on the body without a giant CMN, is a rare disease comprising about 4% of patients with CMN. Because MCMN accompanies neurodevelopmental delay, including seizures in 25% of patients as well as the risk of malignant melanoma, it must be carefully followed-up. We report a case of MCMN with developmental delay in a 19-month-old Korean boy. He had a history of febrile seizure when he was 18 months old. He showed a speech delay after the 1-year-follow up, even though there was no evidence of neurocutaneous melanosis (NCM) on brain magnetic resonance imaging (MRI) at the first visit. As MRI has a low sensitivity for detecting NCM in patients with MCMN older than 4-months, close neurodevelopmental assessments should be considered to provide a chance for early rehabilitation.

Clinical outcome of prenatally diagnosed isolated fetal ventriculomegaly: retrospective analysis of 175 cases / 대한산부인과학회지

OBJECTIVE: The objective of this study is to evaluate the natural course, postnatal outcome, and association between the degree of ventriculomegaly and neurodevelopmental delay in isolated fetal ventriculomegaly. METHODS: We reviewed the medical records of pregnant women diagnosed with isolated fetal ventriculomegaly from October 1996 to June 2004. We defined mild ventriculomegaly as atrial width of 10-14.9 mm and overt ventriculomegaly as 15 mm or more. Neonatal brain ultrasonography was performed in all cases and brain MRI was performed as necessary. Neurodevelopmental outcome was evaluated by medical records and telephone interviews. We analyzed the final outcome of isolated fetal ventriculomegaly according to the ventricular width. RESULTS: There were 175 cases of isolated fetal ventriculomegaly, with a large proportion of male fetuses (68.6%), and one case of trisomy 21. While the group with prenatally resolved ventriculomegaly (n=119) had a smaller ventricular width and more unilaterality, there was no resolution in cases with a ventricular width of 15 mm or more. One hundred and thirty one fetuses with an initial ventricular width of 10 to 11.9 mm had no developmental delay, however, there were 2 cases of cerebral palsy and 2 cases of genetic disorder. Seventeen fetuses had ventricular dilatation of 15 mm or more, with 6 corresponding cases of developmental delay and one case of cerebral palsy. CONCLUSION: Among isolated fetal ventriculomegaly, mild, unilateral or stable ventriculomegaly seems to have a favorable neurological outcome, especially those cases with ventricular width of less than 12 mm. However, management of the condition and counseling of parents are still crucial, because it can be a marker of genetic disorder or brain developmental delay.