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Frontiers in Pediatrics 2024A diagnosis of Silver-Russell syndrome (SRS), a rare imprinting disorder responsible for foetal growth restriction, is considered for patients presenting at least four...
BACKGROUND
A diagnosis of Silver-Russell syndrome (SRS), a rare imprinting disorder responsible for foetal growth restriction, is considered for patients presenting at least four criteria of the Netchine-Harbison clinical scoring system (NH-CSS). Certain items of the NH-CSS are not assessable until the age of 2 years. The objective was to determine perinatal characteristics of children with SRS to allow an early diagnosis.
METHODS
We retrospectively compared the perinatal characteristics of children with SRS ( = 17) with those of newborns small for gestational age (SGA) due to placental insufficiency (PI) ( = 21).
RESULTS
Children with SRS showed earlier and more severely altered foetal biometry than SGA newborns due to PI. Twenty-three percent of patients with SRS showed uterine artery Doppler anomalies. SRS children were significantly smaller at birth (birth length <-3 SDS in 77% of cases in the SRS group vs. 15% in the PI group, = 0.0001).
CONCLUSION
The diagnosis of SRS must be evoked in the neonatal period for SGA newborns with a growth delay present from the second trimester of pregnancy, a birth length <-3 SDS and a relative macrocephaly. Doppler anomalies, classically used to orient the cause of SGA towards PI, did not rule out the diagnosis of SRS.
PubMed: 38638586
DOI: 10.3389/fped.2024.1367433 -
Iranian Journal of Child Neurology 2024Gangliosidosis is one of the hereditary metabolic diseases caused by the accumulation of Gangliosid in the central nervous system, leading to severe and progressive...
ABSTRACT
Gangliosidosis is one of the hereditary metabolic diseases caused by the accumulation of Gangliosid in the central nervous system, leading to severe and progressive neurological deficits. Regarding phenotype, GM1 and GM2-Gangliosidosis are divided into Infantile, Juvenile, and Adult.
MATERIALS & METHODS
In this study, thirty-seven patients with GM1 and GM2-Gangliosidosis were referred to the neurology department of Mofid Children's Hospital in Tehran, Iran, whose disease was confirmed from September 2019 to December 2021. This study assessed age, sex, and developmental status before the onset of the disease, clinical manifestations, brain imaging, and electroencephalography.
RESULTS
97.20% of patients were the result of family marriage. Approximately 80% of juvenile patients were developmentally normal before the onset of the disease. Developmental delay was more common among infantile GM1-Gangliosidosis than infantile GM2-Gangliosidosis, but in total, more than 50% of GM1&GM2-Gangliosidosis patients had reached their developmental milestone before the onset of the disease. With the onset of disease symptoms, 100% of patients regressed in terms of movement, 97.20% of them mentally, and 75% of them had seizures during the disease. The most common clinical findings were cherry-red spot, Mongolian spot, macrocephaly, organomegaly, hyperacusis, and scoliosis. The most common brain imaging findings included bilateral thalamus involvement, brain atrophy, PVL, and delayed myelination. The most common finding in electroencephalography was background low voltage with abnormal sharp waves.
CONCLUSION
This study concluded that most of the patients are the result of family marriage, and most of the juvenile patients are developmentally normal before the onset of the disease. In addition, more than 50% of infantile patients reach their developmental milestones before the onset of the disease. The most common clinical findings of these patients are seizures, cherry-red spot, macrocephaly, hyperacusis, Mongolian spot, and bilateral involvement of the thalamus.
PubMed: 38617391
DOI: 10.22037/ijcn.v18i2.40751 -
European Journal of Human Genetics :... Apr 2024The 16p11.2 deletion syndrome is a clinically heterogeneous disorder, characterized by developmental delay, intellectual disability, hyperphagia, obesity, macrocephaly...
The 16p11.2 deletion syndrome is a clinically heterogeneous disorder, characterized by developmental delay, intellectual disability, hyperphagia, obesity, macrocephaly and psychiatric problems. Cases with 16p11.2 duplication syndrome have similar neurodevelopmental problems, but typically show a partial 'mirror phenotype' with underweight and microcephaly. Various copy number variants (CNVs) of the chromosomal 16p11.2 region have been described. Most is known about the 'typical' 16p11.2 BP4-BP5 (29.6-30.2 Mb; ~600 kb) deletions and duplications, but there are also several published cohorts with more distal 16p11.2 BP2-BP3 CNVs (28.8-29.0 Mb; ~220 kb), who exhibit clinical overlap. We assessed 100 cases with various pathogenic 16p11.2 CNVs and compared their clinical characteristics to provide more clear genotype-phenotype correlations and raise awareness of the different 16p11.2 CNVs. Neurodevelopmental and weight issues were reported in the majority of cases. Cases with distal 16p11.2 BP2-BP3 deletion showed the most severe obesity phenotype (73.7% obesity, mean BMI SDS 3.2). In addition to the more well defined typical 16p11.2 BP4-BP5 and distal 16p11.2 BP2-BP3 CNVs, we describe the clinical features of five cases with other, overlapping, 16p11.2 CNVs in more detail. Interestingly, four cases had a second genetic diagnosis and 18 cases an additional gene variant of uncertain significance, that could potentially help explain the cases' phenotypes. In conclusion, we provide an overview of our Dutch cohort of cases with various pathogenic 16p11.2 CNVs and relevant second genetic findings, that can aid in adequately recognizing, diagnosing and counseling of individuals with 16p11.2 CNVs, and describe the personalized medicine for cases with these conditions.
PubMed: 38605127
DOI: 10.1038/s41431-024-01601-2 -
Frontiers in Endocrinology 2024Silver-Russell syndrome (SRS, OMIM, 180860) is a rare genetic disorder with a wide spectrum of symptoms. The most common features are intrauterine growth retardation...
Silver-Russell syndrome (SRS, OMIM, 180860) is a rare genetic disorder with a wide spectrum of symptoms. The most common features are intrauterine growth retardation (IUGR), poor postnatal development, macrocephaly, triangular face, prominent forehead, body asymmetry, and feeding problems. The diagnosis of SRS is based on a combination of clinical features. Up to 60% of SRS patients have chromosome 7 or 11 abnormalities, and <1% show abnormalities in IGF2 signaling pathway genes (, , and ). The underlying genetic cause remains unknown in about 40% of cases (idiopathic SRS). We report a novel variant c.[-6-2A>G] (NM_000612) in a child with severe IUGR and clinical features of SRS and confirm the utility of targeted exome sequencing in patients with negative results to common genetic analyses. In addition, we report that long-term growth hormone treatment improves height SDS in this patient.
Topics: Child; Female; Humans; Silver-Russell Syndrome; Growth Hormone; Paternal Inheritance; Phenotype; Human Growth Hormone; Fetal Growth Retardation; Insulin-Like Growth Factor II
PubMed: 38596219
DOI: 10.3389/fendo.2024.1364234 -
Pediatric Neurology Jun 2024
Topics: Humans; Drug Resistant Epilepsy; Repressor Proteins; Phenotype; Intellectual Disability; Mutation; Facies; Male; Female; Abnormalities, Multiple; Child; Bone Diseases, Developmental; Megalencephaly; Tooth Abnormalities
PubMed: 38593730
DOI: 10.1016/j.pediatrneurol.2024.03.011 -
Molecular Syndromology Mar 2024Weaver syndrome (WS) is a rare autosomal dominant disorder characterized by distinctive facial features, pre- and post-natal overgrowth, macrocephaly, and variable...
INTRODUCTION
Weaver syndrome (WS) is a rare autosomal dominant disorder characterized by distinctive facial features, pre- and post-natal overgrowth, macrocephaly, and variable developmental delay. The characteristic facial features are ocular hypertelorism, a broad forehead, almond-shaped palpebral fissures and, in early childhood, large, fleshy ears, a pointed "stuck-on" chin with horizontal skin creases, and retrognathia. Heterozygous pathogenic/likely pathogenic variants in the enhancer of zeste homolog 2 () gene are responsible for WS.
CASE PRESENTATION
Here, we report a male patient with a heterozygous likely pathogenic variant in EZH2 gene who has tall stature, distinctive facial features, mild development delay, hypoxic-ischemic encephalopathy with a MRI finding of periventricular leukomalacia, gingival hypertrophy, and early onset high hypermetropia.
CONCLUSION
This case demonstrates the importance of reporting detailed molecular and clinical findings in patients to expand the genotypic and phenotypic findings of this rare syndrome.
PubMed: 38585548
DOI: 10.1159/000533733 -
SAGE Open Medical Case Reports 2024Germline pathogenic variants found in the phosphatase and tensin homolog gene are associated with a range of rare syndromes that collectively fall under the umbrella of...
Germline pathogenic variants found in the phosphatase and tensin homolog gene are associated with a range of rare syndromes that collectively fall under the umbrella of phosphatase and tensin homolog hamartoma tumor syndromes. Due to the wide array of possible clinical presentations and the varying degrees of symptom severity, many individuals with phosphatase and tensin homolog hamartoma tumor syndromes might remain undiagnosed for an extended period. We describe a case of a male child who received the diagnosis at the age of 12. His clinical features included macrocephaly, hypertrophy in the left arm, thyroid nodules, penile freckles, developmental delay, and an autism spectrum disorder. Whole exome sequencing revealed a de novo heterozygous variant in the phosphatase and tensin homolog. The case highlights the diverse and complex nature of phosphatase and tensin homolog hamartoma tumor syndromes, emphasizing the necessity for early diagnosis, multidisciplinary care, and surveillance protocols, offering the potential for improved prognostic outcomes and enhanced quality of life for affected individuals.
PubMed: 38585419
DOI: 10.1177/2050313X241245317 -
Obesity Research & Clinical Practice 2024We present for the first-time efficacy and tolerability of GLP-1-RA (Semaglutide) in Smith-Kingsmore syndrome (SKS). SKS is a rare genetic disorder characterized by...
We present for the first-time efficacy and tolerability of GLP-1-RA (Semaglutide) in Smith-Kingsmore syndrome (SKS). SKS is a rare genetic disorder characterized by intellectual disability, macrocephaly, seizures and distinctive facial features due to MTOR gene mutation. We present a 22-year-old woman with mosaic SKS and severe obesity (Body Mass Index ≥40 kg/m²), treated with semaglutide. She achieved a 9 kg (7.44%) weight loss over 12 months without adverse effects.This case highlights semaglutide's potential in managing obesity in SKS patients, emphasizing the need for further research in this rare genetic disorder.
Topics: Humans; Female; Glucagon-Like Peptides; Young Adult; Mutation; Weight Loss; TOR Serine-Threonine Kinases; Intellectual Disability; Obesity; Treatment Outcome; Body Mass Index; Obesity, Morbid
PubMed: 38582735
DOI: 10.1016/j.orcp.2024.03.009