Clinical spectrum and follow‐up in six individuals with Lamb–Shaffer syndrome (<scp>SOX5</scp>)

Innella, Giovanni; Greco, Donatella; Carli, Diana; Magini, Pamela; Giorgio, Elisa; Galesi, Ornella; Romano, Corrado; Brusco, Alfredo; Graziano, Claudio

doi:10.1002/ajmg.a.62001

Cited by 9 publications

(6 citation statements)

References 19 publications

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“…After literature mining, a total of 111 patients were reviewed including the new cohort of 20 reported here 1,12,[17][18][19][20][21][22][23][24][25][26][27] (Table 1, Supplementary Table 2). Gender distribution was similar between groups (59 males and 52 females) and the mean age at diagnosis (calculated in available cases) was 6.9 ± 3 years (Figure 3.…”

Section: Resultsmentioning

confidence: 99%

Lamb–Shaffer syndrome: 20 Spanish patients and literature review expands the view of neurodevelopmental disorders caused by SOX5 haploinsufficiency

Tenorio‐Castano,

Gómez,

Coronado

et al. 2023

Clinical Genetics

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Lamb–Shaffer Syndrome (LSS; OMIM #616803; ORPHA #313892; ORPHA #313884) is an infrequent genetic disorder that affects multiple aspects of human development especially those related to the development of the nervous system. LSS is caused by variants in the SOX5 gene. At the molecular level, SOX5 gene encodes for a transcription factor containing a High Mobility Group (HMG) DNA‐Binding domain with relevant functions in brain development in different vertebrate species. Clinical features of Lamb–Shaffer syndrome may include intellectual disability, delayed speech and language development, attention deficits, hyperactivity, autism spectrum disorder, visual problems and seizures. Additionally, patients with the syndrome may present distinct facial dimorphism such as a wide mouth with full lips, small chin, broad nasal bridge, and deep‐set eyes. Other physical features that have been reported in some patients include short stature, scoliosis, and joint hypermobility. Here, we report the clinical and molecular characterization of a Spanish LSS cohort of new 20 patients and review all the patients published so far which amount for 111 patients. The most frequent features included developmental delay, intellectual disability, visual problems, poor speech development and facial dysmorphic features. Strikingly, pain insensitivity and hypermetropia seems to be more frequent than previously reported, based on the frequency seen in the Spanish cohort. Eighty‐three variants have been reported so far, single nucleotide variants (SNV) and copy number variants represent 47% and 53%, respectively, from the total of variants reported. Similarly to previous reports, the majority of the SNVs variants of the novel patients reported herein fall in the HMG domain of the protein. However, new variants, affecting other functional domains, were also detected. In conclusion, LLS is a rare genetic disorder mostly characterized by a wide range of developmental and neurological symptoms. Early diagnosis would allow to start of care programs, clinical follow up, prospective studies and appropriate genetic counseling, to promote clinical and social improvement to have profound lifelong benefits for patients and their families. Further research is needed to better understand the underlying mechanisms of the syndrome related to SOX5 haploinsufficiency.

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Section: Resultsmentioning

confidence: 99%

Lamb–Shaffer syndrome: 20 Spanish patients and literature review expands the view of neurodevelopmental disorders caused by SOX5 haploinsufficiency

Tenorio‐Castano,

Gómez,

Coronado

et al. 2023

Clinical Genetics

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“…Hypotonia, ophthalmic features, and scoliosis are also commonly reported [ 1 , 6 , 9 ]. Approximately 1/4 of reported cases showed seizures with a positive response to medication, followed by a benign course [ 7 , 12 ].…”

Section: Discussionmentioning

confidence: 99%

“…Notably, all of the LAMSHF cases were caused by heterozygous variations . The majority of the cases were reported with SOX5 deletion and point variation, including 18 cases with missense variation (12 types), 13 cases with nonsense variation (9 types), and 3 cases with shift variation (3 types) [ 6 , 7 , 11 , 13 ]. Our case was tested with the nonsense point variant c.1477C > T (p. R493 *), which will lead to premature termination and absence of the HMG domain in the translated protein.…”

Section: Discussionmentioning

confidence: 99%

Clinical characterization of Lamb-Shaffer syndrome: a case report and literature review

Zhu

Dong

et al. 2023

BMC Med Genomics

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Background Lamb-Shaffer syndrome (LAMSHF, MIM 616,803) is a rare neurodevelopmental disorder due to haploinsufficiency of SOX5. Furthermore, studies about the clinical features of LAMSHF patients with same allele of c.1477C > T (p. R493*) are very limited. Case presentation We analyzed the phenotypes of one of our cases and two previously reported cases with c.1477C > T (p. R493*), and reviewed the correlating literature. A de novo heterozygous variation c.1477C > T (p. R493*) in SOX5 was identified in a 4 years and 2 months old boy with global development delay by trio-based whole exome sequencing. We compared our case and previously 2 cases reported with recurrent variation, the overlapping clinical features are global developmental delay or intellectual disability, language delay and scoliosis, but their other clinical characteristics are different. Conclusions This study suggests that the clinical features of LAMSHF patients with recurrent variations in the SOX5 gene are different. It is suggested that the LAMSHF-related SOX5 gene should be screened and included as one of the candidate genes for neurodevelopmental disorders of unknown etiology.

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“…Variants in the SOX5 gene have been described in association with the LAMSHF, which can be detected by array-CGH [3,5] or WES [10]. The majority are nonsense and missense variants [1].…”

Section: Discussionmentioning

confidence: 99%

“…LAMSHF is characterized by developmental delay, intellectual disability, poor expressive speech and mild dysmorphic facial features [1,2,5,10,11]. In addition, ophthalmological alterations and skeletal abnormalities [12,13] can also be shown in these patients.…”

Section: Introductionmentioning

confidence: 99%

A novel mutation in the SOX5 gene c.1627del; p.(Tyr543IlefsTer14) is associated to Lamb–Shaffer syndrome: a case report

Alcocel

Álamo

Salvador-Rupérez

et al. 2023

Egypt J Med Hum Genet

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Background Lamb–Shaffer syndrome (LAMSHF) is a rare neurodevelopmental disorder caused by heterozygous mutation or microdeletion involving the SOX5 gene. LAMSHF is characterize by developmental delay, intellectual disability, poor expressive speech, mild dysmorphic facial features and skeletal abnormalities. Case presentation We presented a case of a child with delayed psychomotor development in all areas, scoliosis, peculiar facies, and suspicion of intermittent endotropia, alteration in the alignment of one foot and difficulty in standing. These clinical features lead to genetics studies, in which a novel pathogenic variant in the SOX5 gene was detected in association with LAMSHF. Conclusions LAMSHF should be suspected in patients with developmental delay, speech delay, intellectual disability, behavioural disturbances, ophthalmological alterations and skeletal abnormalities. A novel pathogenic mutation in the SOX5 gene c.1627del p.(Tyr543IlefsTer14) was identified in this patient as responsible of Lamb–Shaffer syndrome. This case contributes to understanding the genetic characteristics, clinical features, and diagnosis of LAMSHF.

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Clinical spectrum and follow‐up in six individuals with Lamb–Shaffer syndrome (SOX5)

Cited by 9 publications

References 19 publications

Lamb–Shaffer syndrome: 20 Spanish patients and literature review expands the view of neurodevelopmental disorders caused by SOX5 haploinsufficiency

Lamb–Shaffer syndrome: 20 Spanish patients and literature review expands the view of neurodevelopmental disorders caused by SOX5 haploinsufficiency

Clinical characterization of Lamb-Shaffer syndrome: a case report and literature review

A novel mutation in the SOX5 gene c.1627del; p.(Tyr543IlefsTer14) is associated to Lamb–Shaffer syndrome: a case report

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