<i>MAGEL2</i>‐related disorders: A study and case series

Patak, Jameson; Gilfert, James; Byler, Melissa; Neerukonda, Vamsee K.; Thiffault, Isabelle; Cross, Laura; Amudhavalli, Shivarajan; Pacio‐Míguez, Marta; Palomares‐Bralo, María; García‐Miñaúr, Sixto; Santos‐Simarro, Fernando; Powis, Zöe; Alcaraz, Wendy; Tang, Sha; Jurgens, Julie A; Barry, Brenda J.; England, Eleina; Engle, Elizabeth C.; Hess, Jonathon; Lebel, Robert Roger

doi:10.1111/cge.13620

Cited by 29 publications

(56 citation statements)

References 40 publications

(153 reference statements)

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“…Yet, since our cohort was initially suspected of having PWS, an inclusion bias may be present. It was recently reported that Chitayat-Hall syndrome was also caused by pathogenic variants in MAGEL2 [12,14]. GH deficiency, which is a characteristic of this syndrome, was found in all three cases in whom GH was evaluated.…”

Section: Discussionmentioning

confidence: 73%

“…Although it was reported that SYS patients have a higher prevalence of ASD [3,5,9], this could not be evaluated due to the severe intellectual disability in most of our patients. Previous studies report that among adolescent patients with SYS, the proportion of those who presented with hyperphagia and obesity was low, unlike that of patients with PWS, and many of those presented with ASD [9,14]. In our study, it was difficult to evaluate patients in these respects because we could only observe two patients until puberty; however, we identified some patients without hyperphagia, obesity, or the personality characteristic of PWS.…”

Section: Discussionmentioning

confidence: 79%

“…Interestingly, in a recent paper, Patak et al produced a review of their cases and a systematic review and found no clinical or genetic differences between SYS and Chitayat-Hall syndrome [14]. In addition, arthrogryposis, which is not found in PWS, was confirmed in all patients as previously reported [3,[5][6][7][8][9][10].…”

Section: Discussionmentioning

confidence: 83%

“…Next, a genotype-phenotype correlation is discussed. Previous reports have mentioned that c.1996dupC is the most common variant, which is more severe than other variants (e.g., frequencies of arthrogryposis, tube feeding, and respiratory dysfunction) [9,14]. In our study, however, Patient 4 (c.1996dupC) had a history of tube feeding during infancy, but did not show respiratory dysfunction, indicating that the patient's condition was comparable to that of other patients at least by the age of 6 years.…”

Section: Discussionmentioning

confidence: 99%

“…Truncating variants in MAGEL2 cause severe arthrogryposis with reduced fetal movement resulting in perinatal death [11]. Recently, pathogenic variants in MAGEL2 were reported as causes of Chitayat-Hall syndrome, which is characterized by distal arthrogryposis, intellectual disability, dysmorphic features and hypopituitarism, and in particular, growth hormone deficiency (OMIM #208080) [12][13][14]. These reports demonstrated that SYS and Chitayat-Hall syndromes are allelic disorders.…”

Section: Introductionmentioning

confidence: 99%

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Schaaf-Yang syndrome shows a Prader-Willi syndrome-like phenotype during infancy

Negishi

Ieda

Hori

et al. 2019

Orphanet J Rare Dis

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Background: Schaaf-Yang syndrome (SYS) is a newly recognized imprinting related syndrome, which is caused by a truncating variant in maternally imprinted MAGEL2 located in 15q11-q13. Yet, precise pathomechanism remains to be solved. We sequenced MAGEL2 in patients suspected Prader-Willi syndrome (PWS) to delineate clinical presentation of SYS. We examined 105 patients with clinically suspected PWS but without a specific PWS genetic alteration. Sanger sequencing of the entire MAGEL2 gene and methylation-specific restriction enzyme treatment to detect the parent of origin were performed. Clinical presentation was retrospectively assessed in detail. Results: Truncating variants in MAGEL2 were detected in six patients (5.7%), including a pair of siblings. All truncating variants in affected patients were on the paternally derived chromosome, while the healthy father of the affected siblings inherited the variant from his mother. Patients with MAGEL2 variants shared several features with PWS, such as neonatal hypotonia, poor suck, and obesity; however, there were also unique features, including arthrogryposis and a failure to acquire meaningful words. Additionally, an episode of neurological deterioration following febrile illness was confirmed in four of the six patients, which caused severe neurological sequalae. Conclusions: SYS can be present in infants suspected with PWS but some unique features, such as arthrogryposis, can help discriminate between the two syndromes. An episode of neurological deterioration following febrile illness should be recognized as an important complication.

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Section: Discussionmentioning

confidence: 73%

Section: Discussionmentioning

confidence: 79%

Section: Discussionmentioning

confidence: 83%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Schaaf-Yang syndrome shows a Prader-Willi syndrome-like phenotype during infancy

Negishi

Ieda

Hori

et al. 2019

Orphanet J Rare Dis

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Longitudinal analysis of electroencephalography pattern changes in an infant with Schaaf‐Yang syndrome and a novel mutation in melanoma antigen L2 (MAGEL2)

Mizuno

Yokoyama

et al. 2022

Molec Gen & Gen Med

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Background Schaaf‐Yang syndrome (SYS) is a rare hereditary disease caused by truncating point mutations of the paternal allele of melanoma antigen L2 (MAGEL2), one of five protein‐coding genes within the Prader‐Willi syndrome (PWS) critical domain. SYS shares many clinical and molecular characteristics with PWS but has some distinct features, such as joint contractures and autism. Patients with PWS show abnormal electroencephalography (EEG) patterns. However, there are very few reports on EEG findings in patients with SYS. Methods A SYS patient was included in this study. Detailed neurological examinations and EEG were performed from neonate to infant ages. Sanger sequencing was performed. Results Our patient presented abnormal EEG findings and had diffuse brain dysfunction symptoms including a reduced level of consciousness, diminished spontaneous movements, hypotonia, feeding difficulties, and hypoventilation from early after birth. As she grew older and her background activity of EEG normalized, her neurodevelopmental symptoms remained but improved. Sanger sequencing of this patient revealed a novel, heterozygous c.2005C > T, truncating mutation in the MEGAL2 gene. Conclusions We described an SYS‐associated, time‐dependent, EEG pattern in a patient with SYS. Our findings of longitudinal EEG changes in a patient with SYS revealed a specific pattern of how affected individuals develop brain function.

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Truncated variants of MAGEL2 are involved in the etiologies of the Schaaf-Yang and Prader-Willi syndromes

Heimdörfer,

Vorleuter,

Eschlböck

et al. 2024

The American Journal of Human Genetics

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MAGEL2‐related disorders: A study and case series

Cited by 29 publications

References 40 publications

Schaaf-Yang syndrome shows a Prader-Willi syndrome-like phenotype during infancy

Schaaf-Yang syndrome shows a Prader-Willi syndrome-like phenotype during infancy

Longitudinal analysis of electroencephalography pattern changes in an infant with Schaaf‐Yang syndrome and a novel mutation in melanoma antigen L2 (MAGEL2)

Truncated variants of MAGEL2 are involved in the etiologies of the Schaaf-Yang and Prader-Willi syndromes

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