Hypogonadotropic Hypogonadism and Kleefstra Syndrome due to a Pathogenic Variant in the<i> EHMT1</i> Gene: An Underrecognized Association

Torga, Ana Patricia; Hodax, Juanita K.; Mori, Mari; Schwab, Jennifer; Quintos, Jose Bernardo

doi:10.1155/2018/4283267

Cited by 10 publications

(12 citation statements)

References 15 publications

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“…Hearing loss occurs in approximately 20% to 30% of affected patients . The audiometric findings in Kleefstra syndrome include sensorineuronal and conductive hearing losses . There have been no reports of vestibular abnormalities.…”

Section: Introductionmentioning

confidence: 99%

Otopathology in Kleefstra Syndrome: A Case Report

et al. 2019

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Kleefstra syndrome is a rare neurogenetic disorder caused by a subtelomeric 9q34.3 deletion or by an intragenic mutation of the euchromatin histone methyl transferase 1 gene (EHMT1). Approximately 20% to 30% of individuals have hearing loss. The left temporal bone of one subject with hearing loss was studied using light microscopy. There were several abnormalities including dysostosis of the stapes without fixation, enlarged vestibular aqueduct, anomalies of the organ of Corti in the basal turn, cyst formation in the stria vascularis, and dysmorphia of the cochlear modiolus and the vestibular labyrinth. This is the first published description of the otopathology in Kleefstra syndrome. Laryngoscope, 130:2028–2033, 2020

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Section: Introductionmentioning

confidence: 99%

Otopathology in Kleefstra Syndrome: A Case Report

et al. 2019

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“…No organ perforation or mechanical cause of obstruction was found. The suspicion of intestinal pseudo-obstruction as part of the un-disability 3 . Even though they are not a part of initial clinical presentation, GI disorders described so far include anal atresia and gastroesophageal reflux 2,3 .…”

Section: Case Reportmentioning

confidence: 99%

“…The suspicion of intestinal pseudo-obstruction as part of the un-disability 3 . Even though they are not a part of initial clinical presentation, GI disorders described so far include anal atresia and gastroesophageal reflux 2,3 . This could be the first case of intestinal pseudo-obstruction as a clinical manifestation of KS1.…”

Section: Case Reportmentioning

confidence: 99%

“…The main phenotypic features arise from haploinsufficiency for the EHMT1 gene 2 . The estimated prevalence is 1 per 200,000 individuals diagnosed with intellectual disability 3 . Gastrointestinal (GI) disorders aren't a part of initial clinical presentation of KS1.…”

Section: Introductionmentioning

confidence: 99%

“…Gastrointestinal (GI) disorders aren't a part of initial clinical presentation of KS1. GI disorders described so far as a part of clinical presentation of KS1 are anal atresia and gastro-oesophageal reflux 2,3 . Intestinal pseudo-obstruction is a gastrointestinal motility disorder characterized by recurrent intestinal obstruction, without evidence of mechanical or anatomical occlusion 4 .…”

Section: Introductionmentioning

confidence: 99%

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Intestinal pseudo-obstruction in a patient with Kleefstra syndrome

Golem

Nikolić

Medančić

et al. 2021

Med. Flum. (Online)

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Aim: To present a case of intestinal pseudo-obstruction in a paediatric patient with Kleefstra syndrome type 1 as a new clinical feature of this rare genetic disorder. Case report: A seven-year-old patient was admitted to the emergency department for nausea and vomiting. Clinical examination showed distended, meteoristic abdomen without detectable peristaltic sound. Abdominal X-ray revealed air-fluid levels and possible right subdiaphragmatic air collection. An urgent exploratory laparotomy was indicated. Intraoperatively, extremely dilated loops of small and large intestine up to the distal sigmoid colon were noted. No anatomical or mechanical causes of obstruction were found. The postoperative course was complicated by dysfunctional intestinal motility and urinary catheter-related infection which required prokinetics and intravenous antibiotic therapy. The patient was transferred to a paediatric centre specialized in intestinal motility disorders for further treatment. Conclusion: This is the first case of intestinal pseudo-obstruction described as a part of clinical presentation of Kleefstra syndrome type 1. Further research and re-evaluation of patients with KS1 is needed to determine if intestinal pseudo-obstruction is a new clinical manifestation depending on the size of the deletion or a repercussion of hypotonia sequential to an underlying syndrome.

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Growth, body composition, and endocrine‐metabolic profiles of individuals with Kleefstra syndrome provide directions for clinical management and translational studies

Bouman,

Geelen,

Kummeling

et al. 2023

American J of Med Genetics Pt A

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Mendelian neurodevelopmental disorders caused by variants in genes encoding chromatin modification can be categorized as Mendelian disorders of the epigenetic machinery (MDEMs). These disorders have significant overlap in molecular pathways and phenotypes including intellectual disability, short stature, and obesity. Among the MDEMs is Kleefstra syndrome (KLFS), which is caused by haploinsufficiency of EHMT1. Preclinical studies have identified metabolic dysregulation and obesity in KLFS models, but proper clinical translation lacks. In this study, we aim to delineate growth, body composition, and endocrine‐metabolic characteristics in a total of 62 individuals with KLFS. Our results revealed a high prevalence of childhood‐onset overweight/obesity (60%; 28/47) with disproportionately high body fat percentage, which aligns perfectly with previous preclinical studies. Short stature was common (33%), likely due to advanced skeletal maturation. Endocrine‐metabolic investigations showed thyroid dysregulation (22%; 9/41), elevated triglycerides, and decreased blood ammonia levels. Moreover, hand radiographs identified decreased bone mineralization (57%; 8/14) and negative ulnar variance (71%; 10/14). Our findings indicate a high (cardio)metabolic risk in KLFS. Therefore, we recommend monitoring of weight and endocrine‐metabolic profile. Supporting a healthy lifestyle and screening of bone mineralization is advised. Our comprehensive results support translational research and contribute to a better understanding of MDEM‐associated phenotypes.

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Hypogonadotropic Hypogonadism and Kleefstra Syndrome due to a Pathogenic Variant in the EHMT1 Gene: An Underrecognized Association

Cited by 10 publications

References 15 publications

Otopathology in Kleefstra Syndrome: A Case Report

Otopathology in Kleefstra Syndrome: A Case Report

Intestinal pseudo-obstruction in a patient with Kleefstra syndrome

Growth, body composition, and endocrine‐metabolic profiles of individuals with Kleefstra syndrome provide directions for clinical management and translational studies

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