A 22q11.2-microdeletiós szindróma klinikai jellemzői

Összefoglaló. Bevezetés: A sokszínű tünetspektrummal jellemezhető DiGeorge-szindróma leggyakoribb oka a 22q11.2-microdeletio; incidenciája 1/4000–6000. Célkitűzés: A DiGeorge-szindrómára gyanús hazai betegcsoport 22q11.2-microdeletióval társult tüneteinek/panaszainak részletes feltérképezése, a betegség incidenciájának becslése és egy magyarországi 22q11.2-microdeletiós szindróma regiszter létrehozása. Módszer: 2005 és 2019 között a Semmelweis Egyetem II. Gyermekgyógyászati Klinikájára DiGeorge-szindróma gyanújával beutalt és a Veleszületett Rendellenességek Országos Nyilvántartása által regisztrált DiGeorge-szindrómás betegek adatait dolgoztuk fel. A fenotípusjegyeket a Humán Fenotípus Ontológia kódrendszer alapján határoztuk meg. Eredmények: A vizsgálatba 114, igazolt DiGeorge-szindrómás és 113, FISH-vizsgálattal microdeletiót nem hordozó, de klinikailag a DiGeorge-szindróma tüneteit mutató beteget vontunk be. A diagnózis felállításakor a betegek átlagéletkora 5,88 (± 9,66 SD) év volt, eddig a betegek 54,9%-a legalább egy szívműtéten átesett. A betegek leggyakoribb tünetei a kamrai sövényhiány, a mélyen ülő fülek, a gótikus szájpad, a motoros fejlődési elmaradás és a visszatérő fertőzések voltak. Megbeszélés: A DiGeorge-szindróma becsült incidenciája hazánkban 1/12 500, közöttük magas a többszörösen veszélyeztetett újszülöttek és a műtéti korrekcióra szorulók aránya. A diagnózis hazánkban 2–3 évvel korábban történik a nemzetközi átlaghoz viszonyítva. Következtetés: A létrehozott regiszterünk alapján Magyarországon a kórkép aluldiagnosztizált. Minden conotruncalis szívfejlődési rendellenesség vagy jelentős kamrai sövényhiány esetén citogenetikai vizsgálat javasolt a DiGeorge-szindróma felmerülő gyanúja miatt. Negatív lelet esetén az atípusos töréspontú microdeletiók azonosítására komparatív genomiális hibridizáció vagy multiplex ligatiofüggő próbaamplifikációs vizsgálat javasolt. A betegek számára multidiszciplináris ellátás szükséges, III-as progresszivitási szintű újszülött intenzív részlegen, gyermekkardiológus és klinikai genetikus részvételével. Orv Hetil. 2022; 163(1): 21–30. Summary. Introduction: The 22q11.2 microdeletion syndrome is the most common cause of DiGeorge syndrome, showing a wide phenotypic spectrum and has an estimated incidence of 1/4000–6000 livebirths. Objective: Detailed characterization of the clinical signs/symptoms associated with 22q11.2 deletion, estimation of the national incidence via establishing a Hungarian register. Method: Retrospective data between 2005 and 2019 from the 2nd Department of Paediatrics, Semmelweis University and from national database of congenital anomalies were obtained. Phenotypic abnormalities were described using the Human Phenotype Ontology nomenclature. Results: A cohort of 114 DiGeorge patients and 113 patients negative for FISH testing were included. The mean age of patients at diagnosis was 5.88 (± 9.66 SD) years and 54.9% of patients had at least one heart surgery until diagnosis. The main identified symptoms were ventricular septal defect, low-set ears, recurrent infections, high narrow palate and motor development delay. Discussion: The estimated incidence of DiGeorge syndrome in Hungary is 1/12 500 births, the frequency of infants at high risk and in need for surgery is high. Diagnosis is established 2–3 years earlier as compared to the international average. Conclusion: Based on the established Hungarian register, the incidence is lower compared to international data. In the case of conotruncal heart anomaly and ventricular septal defects, cytogenetic testing is recommended for the increased probability of DiGeorge syndrome. For second-tier testing, comparative genome hybridization or multiplex ligation-dependent probe amplification are recommended to identify atypical microdeletions. Newborns with DiGeorge syndrome require special care in perinatal intensive centers including pediatric cardiology and genetic counseling. Orv Hetil. 2022; 163(1): 21–30.

Speech development in children of preschool age with arthrogryposis multiplex congenital with upper limb deformities

BACKGROUND: The difficulties or gross disturbance in motor development, which are diagnosed in children at an early age, are one of the prognostic markers of further problems in their speech development. AIM: This study aimed to determine the speech development of children with arthrogryposis multiplex congenita with upper limb deformities. MATERIALS AND METHODS: Speech examination was conducted in 21 children with arthrogryposis multiplex congenita preschool age (average age: 5.16 1.49 years) from 2020 to 2021. Patients were divided into 2 groups: group 1 (10 people) with children of younger and middle preschool age (average age 3.81 0.63 years) and group 2 (11 people) with children of older and preparatory preschool age (average age 6.39 0.78 years). The speech examination results were exposed to statistical analysis. RESULTS: The majority of children with arthrogryposis multiplex congenita had speech pathology (90.5%), whereas general speech underdevelopment dominated over speech development delay (78.9% and 21.1%, respectively). A high frequency of perinatal hypoxic-ischemic encephalopathy in children with arthrogryposis multiplex congenita (80.9%), a complicated perinatal anamnesis (57.1%), and a delay in early motor or speech development (100% and 52.4%, respectively) links with speech disorder development in the future. Patients with arthrogryposis have a large percentage of congenital pathology of the articulatory apparatus structure (57.1%). Of the children, 76.2% were with a total form of arthrogryposis multiplex congenita, whereas 23.8% with an isolated upper extremity lesion. No statistically significant differences were determined in the form of speech pathology between patients with various forms of arthrogryposis multiplex congenita. Children of the first age group had speech disorders in 90% of cases, whereas 90.9% in group 2. Based on the form of speech pathology, patients with general speech underdevelopment and speech development delay were determined in group 1 (55.6% and 44.4%, respectively), whereas children with general speech underdevelopment in group 2 (100%). In the clinical form of speech pathology, dysarthria prevailed in children of both age groups (80%). CONCLUSIONS: Children with arthrogryposis multiplex congenita with upper limb deformities have a high incidence of speech disorders. Early speech examination and speech therapy eliminated all detected disturbances.

Fundamental Motor Skill Delays in Preschool Children With Disabilities: 2012 National Youth Fitness Survey

Delays in fundamental motor skill (FMS) competency have been observed in a variety of children with disabilities. However, evidence of FMS delays is largely limited to small, geographically specific, limitedly diverse, and non-representative samples. The purpose of this study was to examine the association between FMS competency and reported disability status among pre-school children, ages 3–5 years, using the 2012 National Youth Fitness Survey (NYFS). In total, 329 preschool children (49% female; 4.00 ± 0.04 years of age) from the 2012 NYFS completed the Test of Gross Motor Development−2, including 43 preschoolers identified with a disability based on parental report (44% female; 4.20 ± 0.16 years). Associations were examined with logistic regression using sampling weights. Poor FMS competency, defined as gross motor quotient scores ≤ 79, was observed in significantly more children with disabilities (29%) than children without disabilities (10%, OR = 3.5, p = 0.04). While not statistically significant, there was a growing disparity in FMS competency at age 5 (41 vs. 11%) compared to age 3 (15 vs. 9%, OR = 1.80, p = 0.30). The results provide additional evidence for poor FMS competency among pre-school children with disabilities. FMS should be an early part of comprehensive assessments for all children suspected of disability or development delay as it is critical to identify and intervene upon FMS delays before discrepancies can widen.

Use of growth hormone in region 19p13.3 microduplication syndrome in girl with central early puberty: a clinical case report

Chromosomal mutations involving 19p13.3 have been described as pathogenic. clinical and phenotypic features can include, in most cases, psychomotor development delay, microcephaly, typical facial appearance, hand and foot anomalies, umbilical hernia, hypotonia, and low percentage of lean mass. The main types of mutation found on this chromosome are deletion or duplication. Short stature is often the cause of medical demand and the use of exogenous GH for patients with this syndrome is not beneficial. This article reports the case of a 5-year-old girl who sought medical help due to short stature and was diagnosed with this syndrome. Furthermore, this case study may contribute to the dissemination in the medical community about the association of this genetic mutation with the child's clinical condition, warning about this syndrome, and the possibility of the occurrence of early puberty. This study was analyzed and approved by the Research Ethics Committee (CEP) according to a substantiated opinion number 4.765.113.

Effects of Microcurrent on Oxygen Saturation by Controlling Rectus Abdominis Activity in Preterm Infant With Desaturation During Feeding: A Pilot Study

Objective: To determine whether a portable microcurrent therapy device (PMTD) of the rectus abdominis muscles is effective for treating desaturation during feeding in preterm infants and to evaluate the association between initial electrical activity of respiratory muscle and long-term development delay.Methods: Twenty preterm infants with desaturation during feeding were recruited. Respiratory muscle activity was quantified by calculating the root mean square (RMS) of the electromyography. All preterm infants received a 30 min PMTD application to the rectus abdominis and diaphragm daily for 2 weeks. RMS of diaphragm and rectus abdominis, feeding volume, frequency of desaturation during feeding at baseline (pre-PMTD) and 1, 2 week post-PMTD were measured. The number of days it took to treat desaturation after PMTD was measured. A Denver developmental screening test was performed and infants were divided into 3 groups: (1) normal; (2) caution; and (3) delayed at 3months after PMTD.Results: The desaturation during feeding of all the preterm infants subsided after PMTD and the mean days took to treat desaturation was 25.4 ± 14.2 days. The RMS of diaphragm, rectus abdominis, and frequency of desaturation during feeding were significantly decreased and the feeding volume was significantly increased after PMTD (p < 0.01). The mean treatment duration for desaturation was negatively correlated with RMS of rectus abdominis at baseline and 1 week post-PMTD, respectively (Pearson's correlation coefficient = −0.461,−0.514, p-value = 0.047, 0.029). RMS of rectus abdominis of Group 3 is lower than that of group 1 and 2 (p < 0.01).Conclusions: This pilot study showed that the microcurrent therapy of rectus abdominis is an efficient therapy for the treatment of preterm infants with desaturation during feeding, especially preterm infants with higher activity of the rectus abdominis. In preterm infants with lower rectus abdominis activity, longer time is required to treat desaturation by microcurrent therapy and developmental delay is observed at months post-treatment.

Frequency-Following Response and Auditory Behavior in Children with Prenatal Exposure to the Zika Virus

Introduction Prenatal exposure to the Zika virus can impair neurodevelopment and cause auditory damage. Objective To analyze the frequency-following response (FFR) and the auditory behavior (with the LittlEars ® questionnaire) of children with and without prenatal exposure to Zika virus infection. Methods A total of 30 children participated in the present study, divided into 3 groups: 10 children with microcephaly and prenatal exposure to the Zika virus; 10 normocephalic children with prenatal exposure to the Zika virus; and 10 children with no evidence of prenatal exposure to the virus. The FFR test was performed with the /da/ syllable. The LittlEars ® questionnaire was used with parents/guardians. Results For the FFR measurements, there was no difference between the groups. The children with exposure to the Zika virus presented a final score in the questionnaire below what is expected from children with normal hearing. A significant difference was observed for the final, semantic, and expressive scores between the group with microcephaly and the other groups. A strong negative correlation was seen between the LittlEars ® questionnaire final score and the FFR measurements for the group with microcephaly when compared with the other groups. Conclusion Children exposed to the Zika virus, with and without microcephaly, presented FFR patterns similar to what was seen in children with no evidence of virus exposure. However, they showed signs of immature auditory behavior, suggesting auditory development delay.

Educational Trip With Teeth Doll to Promote Dental Health in Preschool-Age Children

The case of children with dental caries in 2017 was found at 79.8 percent and 82.83 percent in 2018 in Public Health Center Cibeber. Preschool-age children visit dental poly in 2018 only 206 children from approximately 1,536 children. Dental caries in a childcause cavities, pain, sleep disorders, and broken teeth, which can cause food absorption disorders that will affect child's growth and development delay, it can decrease child's level of intelligence, so preschool-age children's awareness of the importance of dental and oral health needs to be increased. Innovative dental health promotion by making the health care as a trip vacation, it was an Educational Trip with Teeth Doll or an E-Bogi Trip. To analyze the innovation of E- Bogi Trip as an effort to promote dental health in preschool-age children used qualitative descriptive methods, research in March through December 2019, at Public Health Center Cibeber Cilegon City, uses a purposive sampling with a deep study analysis technique. E-Bogi Trip has matched the characteristics of innovation, having interesting ideas with visual media and teeth doll, has a new idea of health promotion, good planning with the governing support, cross programs, cross sectors and the goals of that innovation can be achieved. Innovation was done well, seen from the increase in preschool-age visits to dental poli in 2019 to 395 children and 569 preschool-age children have an ability on dental care. It’s was matched the characteristics of innovation and can increase efforts to promote preschool-age children's dental health, which is expected to achieve good dental health and can develop optimally.

A Chinese Case of Cornelia de Lange Syndrome Caused by a Pathogenic Variant in SMC3 and a Literature Review

PurposeCornelia de Lange syndrome (CdLS) is a rare congenital developmental disorder, and cases caused by variants in SMC3 are infrequent. This article describes a case of CdLS related to a pathogenic variant in SMC3 and performs a literature review.MethodsWe collected clinical data and biological samples from a 12-year-old boy with “short stature for 11 years”. Gene variants in the proband were detected by whole-exome sequencing, and the variants in his parents were verified by Sanger sequencing. All SMC3-related CdLS patients from the PubMed and Web of Science databases were collected and summarized using the available data.ResultsA pathogenic variant in SMC3 in the proband, c.1942A>G, was identified. Neither of his parents carried the same variant. Twenty-eight patients were diagnosed with CdLS with variants in SMC3, including the cases in this study and those reported in the literature, where half of the variant types were missense, followed by 32% (9/28) with a deletion and 11% (3/28) with a duplication. All patients showed symptoms of verbal development delay and intellectual disability to different degrees, and 90% patients had long eyelashes while 89% patients had arched eyebrows.ConclusionThis study summarized different gene variants in SMC3 and the frequencies of the various clinical manifestations according to the reported literature. For CdLS caused by SMC3 variants, short stature and facial dysmorphic features are the two most important clinical clues. Definite diagnosis of this rare disease may be challenging clinically; thus, it is significant to use molecular diagnosis.

Case Report: Second Report of Joubert Syndrome Caused by Biallelic Variants in IFT74

Joubert syndrome (JBTS) is a rare ciliopathy characterized by developmental delay, hypotonia, and distinctive cerebellar and brain stem malformation called the molar tooth sign (MTS). We reported a 15-month-old female with dysmorphic features (flat nasal bridge, almond-shaped eye, and a minor midline notch in the upper lips), hypotonia, polydactyly, development delay, and MTS. Whole exome sequencing revealed biallelic heterozygous mutations c.535C>G(p.Q179E/c.853G>T) (p.E285*) in IFT74, which were inherited from the parents. So far, only one article reported JBTS associated with IFT74 gene mutation, and this is the second report of the fifth patient with JBTS due to variants in IFT74. All five patients had developmental delay, postaxial polydactyly, subtle cleft of the upper lip, hypotonia, and MTS, but notably without renal and retinal anomalies or significant obesity, and they shared the same mutation c.535C>G(p.Q179E) in IFT74, and c.853G>T(p.E285*) that we found was a new mutation in IFT74 that related with Joubert syndrome. Those findings highlight the need for the inclusion of IFT74 in gene panels for JBST testing.

Copy number variations of chromosome 17p11.2 region in children with development delay and in fetuses with abnormal imaging findings

Background Deletion and duplication of the 3.7 Mb region in 17p11.2 result in two syndromes, Smith-Magenis syndrome and Potocki-Lupski syndrome, which are well-known development disorders. The purpose of this study was to determine the prevalence, genetic characteristics and clinical phenotypes of 17p11.2 deletion/duplication in Chinese children with development delay and in fetuses with potential congenital defects. Methods 7077 children with development delay and/or intellectual disability were screened by multiplex ligation-dependent probe amplification P245 assay. 7319 fetuses with potential congenital defects were tested using next generation sequencing technique. Results 417 of 7077 pediatric patients were determined to carry chromosome imbalance. 28 (28/7077, 0.4%) cases had imbalance at chromosome 17p11.2. Among them, 12 cases (42.9%) had heterozygous deletions and 16 cases (57.1%) had heterozygous duplications. The clinical phenotypes were variable, including neurobehavioral disorders, craniofacial/skeletal anomalies, immunologic defects, ocular problems and organ malformations. 263 of 7319 fetuses were recognized to have genomic copy number variations. Only 2 of them were found to harbor 17p11.2 imbalance. The fetus with deletion presented with ventricular septal defect and the fetus with duplication had cerebral ventricle dilation. Conclusion Our study highlights the phenotypic variability associated with 17p11.2 variations in China. The results further expand the phenotypic spectrum of SMS/PTLS and increase awareness of these disruptive mutations among clinicians.