OBJECTIVES

This study aimed to describe the demographic profile, intervention sessions, goal attainment scaling (GAS), and health-related quality of life (HRQOL) of autistic children receiving speech and language therapy (SLT) in a higher educational institution in the Philippines.

Deidentified data from 18 autistic children aged 4–16 years (mean=8.2; SD=2.9) who received SLT for two months were analyzed. Their demographic profile, intervention sessions, GAS scores, and generic HRQOL scores were documented.

Most participants were school-age children (n=12; 66%) and were boys (n=14; 78%). After two months, the GAS scores of 11 participants (61%) increased by 1–2 points, whereas the scores of the remaining participants decreased (n=6; 33%) or did not change (n=1; 6%). Their mean generic HRQOL scores before and after SLT were 65.6 (SD=15.2) and 61.2 (SD=17.4), respectively.

While the GAS scores increased for most participants, their generic HRQOL scores did not show clinically significant changes after two months of SLT. This can be attributed to the few therapy sessions and short follow-up period. The findings highlight the need to provide long-term support to SLT services of autistic children in the Philippines to document more desirable quality of life outcomes.

Child ; Humans ; Speech ; Physicians, Primary Care ; Language Development Disorders/diagnosis* ; Speech Disorders

OBJECTIVE: To explore the clinical characteristics and genetic etiology for two children with Neurodevelopmental disorder with hypotonia, stereotypic hand movements, and impaired language (MEDHSIL). METHODS: Two children who had visited the Ningbo Women and Children's Hospital on October 15, 2021 were selected as the study subjects. Whole exome sequencing (WES) was carried out for both patients. Candidate variants were verified by Sanger sequencing of their family members. RESULTS: The two children were respectively found to harbor a heterozygous c.138delC (p.Ile47Serfs*42) variant and a c.833del (p.L278*) variant of the MEF2C gene. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), both variants were predicted to be pathogenic (PVS1+PS2+PM2_Supporting). CONCLUSION The c.138delC and c.833del variants of the MEF2C gene probably underlay the pathogenesis of MEDHSIL in the two children. Above findings have enriched the mutational spectrum of the MEF2C gene and enabled genetic counseling for their families.
Child ; Humans ; Family ; Genetic Counseling ; Language ; MEF2 Transcription Factors/genetics* ; Muscle Hypotonia/genetics* ; Neurodevelopmental Disorders

OBJECTIVE: To explore the clinical and genetic characteristics of a boy with isolated maternal uniparental disomy of chromosome 20 [UPD(20)mat]. METHODS: A child who was admitted to the Tongji Hospital Affiliated to Tongji Medical College of Huazhong University of Science and Technology on April 8,2021. was selected as the study subject. Phenotypic and endocrinological findings of the child were retrospectively analyzed. Whole exome sequencing (WES) and methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) were carried out for detecting the UPD sequences and copy number variations. Both of his parents were verified by Sanger sequencing. Relevant literature was systematically reviewed. RESULTS: The child, a 3-year-and-8-month-old boy born to a 41-year-old mother by Cesarean delivery at 36⁺² gestational weeks due to oligohydramia, had a birth weight of 2 300 g and length of 46 cm. He was admitted to the NICU for feeding difficulties which had persisted despite of clinical management. At the age of 3.75, he had a height of 92.5 cm (< 3rd percentile; 25th ~ 50th percentile at 2.5 years) and a weight of 10.8 kg (< 3rd percentile; 50th percentile at 15 months). He had also presented with growth retardation, short stature, attention deficit and hyperactivity disorder (ADHD), mild mental retardation, and speech and language development disorders. He had simian creases in both hands but no additional dysmorphic signs, and his motor development was normal. Serum insulin, thyroid-stimulating hormone, and insulin growth factor binding protein 3 levels were within the normal ranges, though insulin growth factor-1 (IGF-1) was slightly decreased. Since that time he had continuously used atomoxetine hydrochloride capsules to control his ADHD. WES and MS-MLPA revealed the existence of UPD (20)mat. CONCLUSION The UPD(20)mat syndrome is characterized by feeding difficulties, growth retardation and short stature. The child in our case has been accompanied by ADHD and speech and language development disorders, which required long-term treatment. For women with advanced maternal age and suggestive phenotypes, genetic testing and counseling should be conducted.
Male ; Pregnancy ; Humans ; Child ; Female ; Infant ; Adult ; Chromosomes, Human, Pair 20 ; DNA Copy Number Variations ; Retrospective Studies ; Uniparental Disomy/genetics* ; Atomoxetine Hydrochloride ; Dwarfism ; Intercellular Signaling Peptides and Proteins ; Language Development Disorders ; Growth Disorders ; Insulins

OBJECTIVE: To analyze the clinical features and genetic variants in two unrelated patients with psychomotor retardation and facial abnormalities, and to explore their genotype-phenotype correlation. METHODS: Clinical data and family history of the two pedigrees were collected. Whole exome sequencing (WES) and Sanger sequencing were carried out to detect the potential variants. RESULTS: Both patients had presented with mental and language retardation, along with growth delay and facial anomalies. They were both found to harbor de novo loss-of-function variants in exon 12 of the ASXL3 gene, namely c.3096dup (p.Pro1033Thrfs*2) and c.3253G>T (p.Gly1085*). Neither variant was reported previously. Combined with their clinical features and genetic finding, both patients were diagnosed with Bainbridge-Ropes syndrome due to pathogenic variants of the ASXL3 gene. CONCLUSION Diagnosis of Bainbridge Ropes syndrome in the two pedigrees has enriched the genotypic and phenotypic spectrum of this disorder and enabled genetic counseling for them.
Child ; China ; Developmental Disabilities/genetics* ; Humans ; Language ; Mutation ; Pedigree ; Phenotype ; Transcription Factors/genetics*

OBJECTIVE: To explore the genetic etiology for a child featuring mental retardation and speech delay. METHODS: Clinical data of the child was collected. DNA was extracted from peripheral blood samples of the child and members of his pedigree. Whole exome sequencing was carried out for the child, and candidate variants were verified by Sanger sequencing. Prenatal diagnosis was provided for his mother upon her subsequent pregnancy. RESULTS: The child has mainly featured mental retardation, speech delay, ptosis, strabismus, photophobia, hyperactivity, and irritability. Whole exome sequencing revealed that he has harbored a pathogenic heterozygous variant of the KAT6A gene, namely c.5314dupA (p.Ser1772fs*20), which was not detected in either of his parents. The child was diagnosed with Arboleda-Tham syndrome. The child was also found to harbor a hemizygous c.56T>G (p.Leu19Trp) variant of the AIFM1 gene, for which his mother was heterozygous and his phenotypically normal maternal grandfather was hemizygous. Pathogenicity was excluded. Prenatal diagnosis has excluded the c.5314dupA variant of the KAT6A gene in the fetus. CONCLUSION The heterozygous c.5314dupA (p.Ser1772fs*20) variant of the KAT6A gene probably underlay the Arboleda-Tham syndrome in this child. Above finding has enabled genetic counseling and prenatal diagnosis for this pedigree.
Child ; Humans ; Male ; Pregnancy ; Histone Acetyltransferases ; Intellectual Disability/genetics* ; Language Development Disorders ; Pedigree

OBJECTIVE: To describe a family with intellectual developmental disorder with autism and speech delay (IDDAS) caused by a splice variant of TBR1 gene. METHODS: A pregnant women with mental retardation, who also had a family history of mental retardation, was admitted to Prenatal Diagnosis Center of WanBei Coal and Electricity Group General Hospital Corporation in April 2019. Molecular genetic tests were performed on the pregnant women and ten other family members to analyze the pathogenic genotype. Functional assays of the pathogenic variant was carried out by minigene technology. With the determination of the genotype, prenatal diagnosis was carried out by amniotic fluid sampling. RESULTS: Through whole exome sequencing, a novel splicing variant (c.1129-1G>C) was identified in the TBR1 gene of the proband, which has co-segregated with the disease phenotype in the family. The results of minigene assay showed abnormal splicing of exon 5. The variant was not detected in the fetal amniotic fluid. Fetal growth and development were normal one year after the birth. CONCLUSION The c.1129-1G>C variant of the TBR1 probably underlay the disease in of the pedigree. Timely prenatal genetic diagnosis and consultation can help to stop the transmission of the pathogenic variant.
Autistic Disorder/genetics* ; China ; Developmental Disabilities ; Female ; Humans ; Infant ; Intellectual Disability/genetics* ; Language Development Disorders ; Pedigree ; Pregnancy ; T-Box Domain Proteins/genetics*

OBJECTIVE: To analyze the clinical features and genetic basis of three children with mental retardation, language impairment and autistic features due to de novo variants of FOXP1 gene. METHODS: Clinical data of the children were collected.Trio-whole exome sequencing was carried out for the children and their parents. Pathogenicity of the variants was analyzed through bioinformatics prediction. RESULTS: All of the children had various degrees of mental retardation in conjunct with language deficit, global developmental delay, abnormal behavior and peculiar facial features, among whom two also developed autism spectrum disorders. The results of genetic testing showed that all three children harbored de novo variants of the FOXP1 gene, namely c.613_c.614delCTinsTA, c.1248delC and c.1393A>G. Two of these were frameshift variants and one was missense variant, which were all rated as pathogenic based on the guidelines of the American College of Medical Genetics (ACMG). Database search suggested that c.613_c.614delCTinsTA and c.1248delC were unreported previously. CONCLUSION For the three children from unrelated families with mental retardation in conjunct with language deficit, global growth delay, abnormal behavior and peculiar facial features, the c.613_ c. 614delCTinsTA, c.1248delC and c.1393A>G variants of the FOXP1 gene may be the pathogenic factors. Above cases have further expanded the genotype-phenotype profile of FOXP1 deficiency syndrome.
Autistic Disorder/genetics* ; Child ; Forkhead Transcription Factors/genetics* ; Genetic Testing ; Humans ; Intellectual Disability/genetics* ; Language Development Disorders/genetics* ; Repressor Proteins/genetics* ; Whole Exome Sequencing

PURPOSE: The Cow's Milk-related Symptom Score (CoMiSS™), which considers crying, regurgitation, stools, skin and respiratory symptoms, was developed as an awareness tool for evaluating cow's milk-related symptoms. The scoring ranges from 0 to 33. A score ≥12 was proposed as being likely cow's milk-related and suggestive of allergy to cow's milk. This study aimed to determine the age-related CoMiSS™ values in presumed healthy infants in Poland.METHODS: This was a cross-sectional study conducted in well-child clinics in two locations. Parents of the presumed healthy infants aged ≤6 months were approached during a routine checkup/vaccination visit. The exclusion criteria were as follows: presence of acute or chronic diseases, preterm delivery, treatment with therapeutic formula, and use of any food supplements (except vitamins) or medications.RESULTS: Data from 226 infants were obtained (median age [Q1–Q3], 4 months [3–4]). The overall median (Q1–Q3) and mean (standard deviation) CoMiSS™ values were 4 (2–7) and 4.7 (3.5), respectively. The 95th percentile was 11. Scores on some, albeit not all, components of the CoMiSS™ significantly differed between age groups (crying, stools) or feeding type groups (stools and skin symptoms). Eleven children (4.9%) scored ≥12.CONCLUSION: This study adds to earlier age-related CoMiSS™ data by providing CoMiSS™ values in presumed healthy infants in Poland.
Child ; Chronic Disease ; Cross-Sectional Studies ; Crying ; Dietary Supplements ; Food Hypersensitivity ; Humans ; Hypersensitivity ; Infant ; Milk ; Parents ; Poland ; Skin

Infantile colic is a common self-limiting condition that causes significant distress to parents and caregivers. There is no clear cause, gold standard remedy or preventative action. The role of the family physician is to rule out sinister causes while providing counselling and reassurance for parents. The mainstay of management is parental support and reassurance while looking out for red flags in the baby such as fever, lethargy, distended abdomen and failure to thrive. This article provides a framework to approaching infantile colic and practical pointers to share with parents.
Caregivers ; Colic ; diagnosis ; therapy ; Crying ; Evidence-Based Medicine ; Humans ; Infant ; Infant Formula ; Infant, Newborn ; Muscle Hypertonia ; diagnosis ; Parenting ; Parents ; Pediatrics ; methods ; Physicians, Family ; Primary Health Care ; methods ; Professional-Patient Relations