Cornelia de Lange Spectrum

Ascaso, Ángela; Arnedo, María; Puisac, Beatriz; Latorre-Pellicer, Ana; del Rincón, Julia; Bueno-Lozano, Gloria; Pié, Juan; Ramos, Feliciano J.

doi:10.1016/j.anpede.2024.04.012

Cited by 1 publication

(8 citation statements)

References 37 publications

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“…CdLS5 (MIM#300882) is caused by HDAC8 gene mutations (MIM*300269) on chromosome Xq13.1 with Xlinked dominant inheritance [2,4,5]. Individuals with HDAC8-related CdLS have a delayed anterior fontanelle closure and more pronounced ocular hypertelorism, hooding of the eyelids, a broader nose, and dental anomalies.…”

Section: Discussionmentioning

confidence: 99%

“…CdLS is characterized by distinct dysmorphic facies, skeletal anomalies, and failure to thrive. Individuals with CdLS usually have pathogenic variants in genes codifying for the cohesin complex like NIPBL (Nipped-B-like protein), SMC1A, SMC3, RAD21, and HDAC8 [2,3]. The additional genes recently described are BRD4, ANKRD11, and MAU2 [2].…”

Section: Introductionmentioning

confidence: 99%

“…Individuals with CdLS usually have pathogenic variants in genes codifying for the cohesin complex like NIPBL (Nipped-B-like protein), SMC1A, SMC3, RAD21, and HDAC8 [2,3]. The additional genes recently described are BRD4, ANKRD11, and MAU2 [2]. The incidence of CdLS is reported at one per 10,000-50,000 newborns [4].…”

Section: Introductionmentioning

confidence: 99%

“…CdLS type 5 (CdLS5), a multisystemic genetic disorder, is caused by the HDAC8 (histone deacetylase 8) gene mutations (MIM*300269) on chromosome Xq13.1 with X-linked dominant inheritance [4,5]. HDAC8 encodes the lysine deacetylase for the SMC3 (structural maintenance of chromosomes 3) subunit of cohesion, which is involved in the release of cohesion complex [2,5]. HDAC8 mutations affect the cohesin acetylation cycle by the loss of HDAC8 activity, resulting in heightened acetylation of SMC3 and ineffective dissolution of the "used" cohesin complex [5].…”

Section: Introductionmentioning

confidence: 99%

“…HDAC8 mutations affect the cohesin acetylation cycle by the loss of HDAC8 activity, resulting in heightened acetylation of SMC3 and ineffective dissolution of the "used" cohesin complex [5]. The common features of CdLS5 similar to typical CdLS are postnatal growth retardation, microcephaly, developmental delay, facial dysmorphism including hooding of eyelids, arched eyebrows, depressed nasal bridge, micrognathia, cleft palate, long philtrum, gastroesophageal reflux disease (GERD), congenital heart disease, limb defects (more in upper limbs), and genitourinary abnormalities [2,[6][7][8][9]. The other features reported in CdLS5 patients are oligodontia, myopia, and atrial septal defect [8].…”

Section: Introductionmentioning

confidence: 99%

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A Classic Cornelia De Lange Syndrome Type 5 (CdLS5) With a De Novo Missense Variation of p.Gly210Arg in the HDAC8 Gene With a Novel Phenotype of Generalized Dystonia

Chhajed,

Lallar,

Gunasekaran

et al. 2024

Cureus

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Cornelia de Lange syndrome (CdLS) is a rare neurodevelopmental disorder characterized by distinct dysmorphic facies, skeletal anomalies, and failure to thrive. CdLS type 5 (CdLS5) is caused by the HDAC8 gene mutations on chromosome Xq13.1 with X-linked dominant inheritance. We report our observation of an individual with CdLS5 with de novo missense mutation presenting with a novel phenotype of generalized dystonia. A four-month-old girl, second born to a non-consanguineous couple, presented with developmental delay, failure to thrive, and spastic quadriparesis. She had a history of intrauterine growth retardation in the third trimester of pregnancy. Facial gestalt was suggestive of CdLS. She had marked axial and appendicular dystonia. A skeletal survey and magnetic resonance imaging (MRI) with magnetic resonance spectroscopy (MRS) brain studies were normal. Genetic testing revealed a heterozygous missense variation c.628G>C in the HDAC8 gene. She was treated with trihexyphenidyl and clonazepam, followed by syndopa. On follow-up assessment at 22 months of age, the dystonia gradually improved but not entirely over time with medication. It is already known that single gene disorders, including SCN1A, SCN2A, KCNQ2, PRRT2, and pyridoxine deficiency, can result in isolated dystonia; we add CdLS5 (HDAC8 variation) to this expanding spectrum.

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Section: Discussionmentioning

confidence: 99%