Ventriculomegaly and cerebellar hypoplasia in a neonate with interstitial 11q 24 deletion in Jacobsen syndrome region

Puvabanditsin, Surasak; Chen, Charlotte Wang; Botwinick, Marissa; Hussein, Karen; Mariduena, Joseph; Mehta, Rajeev

doi:10.1002/ccr3.1560

Cited by 4 publications

(6 citation statements)

References 20 publications

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“…Neuromotor impairment, growth delay and facial dysmorphisms may be associated with haploinsufficiency of ST3GAL4 (ST3 beta-galactoside alpha-2,3-sialyltransferase 4, MIM:104240) [ 9 ], KIRREL3 (kirre like nephrin family adhesion molecule 3, MIM:607761) and BARX2 (BARX homeobox 2, MIM:604823) genes, while thrombocytopenia and other hematopoietic defects with that of FLI1 (Fli-1 proto-oncogene, ETS transcription factor, MIM:193067) [ 2 , 3 , 13 , 14 ]. They are, indeed, all deleted in both our probands.…”

Section: Discussionmentioning

confidence: 99%

Jacobsen syndrome and neonatal bleeding: report on two unrelated patients

et al. 2021

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Introduction In 1973, Petrea Jacobsen described the first patient showing dysmorphic features, developmental delay and congenital heart disease (atrial and ventricular septal defect) associated to a 11q deletion, inherited from the father. Since then, more than 200 patients have been reported, and the chromosomal critical region responsible for this contiguous gene disorder has been identified. Patients’ presentation We report on two unrelated newborns observed in Italy affected by Jacobsen syndrome (JBS, also known as 11q23 deletion). Both patients presented prenatal and postnatal bleeding, growth and developmental delay, craniofacial dysmorphisms, multiple congenital anomalies, and pancytopenia of variable degree. Array comparative genomic hybridization (aCGH) identified a terminal deletion at 11q24.1-q25 of 12.5 Mb and 11 Mb, in Patient 1 and 2, respectively. Fluorescent in situ hybridization (FISH) analysis of the parents documented a de novo origin of the deletion for Patient 1; parents of Patient 2 refused further genetic investigations. Conclusions Present newborns show the full phenotype of JBS including thrombocytopenia, according to their wide 11q deletion size. Bleeding was particularly severe in one of them, leading to a cerebral hemorrhage. Our report highlights the relevance of early diagnosis, genetic counselling and careful management and follow-up of JBS patients, which may avoid severe clinical consequences and lower the mortality risk. It may provide further insights and a better characterization of JBS, suggesting new elements of the genotype-phenotype correlations.

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Section: Discussionmentioning

confidence: 99%

Jacobsen syndrome and neonatal bleeding: report on two unrelated patients

et al. 2021

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“…Further characteristics include SGA, hypotonia, postnatal growth retardation, delayed psychomotor development, and mild to severe degree of intellectual disability. Brain anomalies have been reported [19], as well as ocular findings including anomalies of extraocular muscles, amblyopia, microcornea, opticus atrophy, macular hypoplasia, and chorioretinal coloboma [20]. Typical facial features include hypertelorism, telecanthus, ptosis, downslanting palpebral fissures, epicanthus, broad nasal bridge and short nose, v-shaped mouth, and small low-set posteriorly rotated ears [4,5].…”

Section: Discussionmentioning

confidence: 99%

Neonatal interstitial lung disease in a girl with Jacobsen syndrome: a case report

et al. 2022

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Background We report a case of the neonatal interstitial lung disease pulmonary interstitial glycogenosis in a girl with Jacobsen syndrome. While Jacobsen syndrome is caused by a deletion on the long arm of chromosome 11 and is genetically confirmed, pulmonary interstitial glycogenosis is of unknown etiology and is diagnosed by lung biopsy. Pulmonary interstitial glycogenosis has not previously been described in association with Jacobsen syndrome. Case presentation A term newborn small for gestational age Caucasian girl presented with respiratory distress, pulmonary hypertension, congenital heart defects, immunodeficiency, and thrombocytopenia. She was diagnosed with Jacobsen syndrome, but also had pulmonary interstitial glycogenosis, which contributed to significant morbidity. There was striking clinical improvement after steroid treatment of the pulmonary interstitial glycogenosis. Conclusions Interstitial lung disease should be considered as a differential diagnosis when respiratory distress and hypoxemia in the perinatal period worsens or persists despite standard treatment. Importantly, pulmonary interstitial glycogenosis may be treatable with corticosteroids. Whether there is a genetic link between pulmonary interstitial glycogenosis and Jacobsen syndrome is still unknown.

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“…Given the acknowledged cerebellar expression of KIRREL3 and its interaction with CASK, we can hypothesize that the KIRREL3 variant is responsible for the cerebellar anomaly of our patient. The only correlation between KIRREL3 and cerebellar abnormality described so far is that of a newborn affected by Jacobsen syndrome, 14 whose brain MRI revealed bilateral ventriculomegaly, enlarged cisterna magna, and cerebellar vermis hypoplasia. The patient carried a 11q24 deletion of 12.3 Mb, encompassing 168 genes; it is therefore extremely difficult to understand if the cerebellar abnormality could be ascribed to KIRREL3 deletion or if it is part of his contiguous genes syndrome.…”

Section: Discussionmentioning

confidence: 99%

A Missense De Novo Variant in the CASK-interactor KIRREL3 Gene Leading to Neurodevelopmental Disorder with Mild Cerebellar Hypoplasia

et al. 2021

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KIRREL3 is a gene important for the central nervous system development—in particular for the process of neuronal migration, axonal fasciculation, and synaptogenesis—and colocalizes and cooperates in neurons with CASK gene. Alterations of KIRREL3 have been linked to neurodevelopmental disorders, ranging from developmental delay, to autism spectrum disorder, to attention deficit/hyperactivity disorder. The underlying mechanism is not yet fully understood, as it has been hypothesized a fully dominant effect, a risk factor role of KIRREL3 partially penetrating variants, and a recessive inheritance pattern. We report a novel and de novo KIRREL3 mutation in a child affected by severe neurodevelopmental disorder and with brain magnetic resonance imaging evidence of mega cisterna magna and mild cerebellar hypoplasia. This case strengthens the hypothesis that dominant KIRREL3 variants may lead to neurodevelopmental disruption; furthermore, given the strong interaction between KIRREL3 and CASK, we discuss as posterior fossa anomalies may also be part of the phenotype of KIRREL3-related syndrome.

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Ventriculomegaly and cerebellar hypoplasia in a neonate with interstitial 11q 24 deletion in Jacobsen syndrome region

Cited by 4 publications

References 20 publications

Jacobsen syndrome and neonatal bleeding: report on two unrelated patients

Jacobsen syndrome and neonatal bleeding: report on two unrelated patients

Neonatal interstitial lung disease in a girl with Jacobsen syndrome: a case report

A Missense De Novo Variant in the CASK-interactor KIRREL3 Gene Leading to Neurodevelopmental Disorder with Mild Cerebellar Hypoplasia

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