Hyperinsulinemic hypoglycemia in seven patients with de novo NSD1 mutations.

Am J Med Genet A 2019 04 4;179(4):542-551. Epub 2019 Feb 4.

Division of Human Genetics, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.

Sotos syndrome is an overgrowth syndrome characterized by distinctive facial features and intellectual disability caused by haploinsufficiency of the NSD1 gene. Genotype-phenotype correlations have been observed, with major anomalies seen more frequently in patients with 5q35 deletions than those with point mutations in NSD1. Though endocrine features have rarely been described, transient hyperinsulinemic hypoglycemia (HI) of the neonatal period has been reported as an uncommon presentation of Sotos syndrome. Eight cases of 5q35 deletions and one patient with an intragenic NSD1 mutation with transient HI have been reported. Here, we describe seven individuals with HI caused by NSD1 gene mutations with three having persistent hyperinsulinemic hypoglycemia. These patients with persistent HI and Sotos syndrome caused by NSD1 mutations, further dispel the hypothesis that HI is due to the deletion of other genes in the deleted 5q35 region. These patients emphasize that NSD1 haploinsufficiency is sufficient to cause HI, and suggest that Sotos syndrome should be considered in patients presenting with neonatal HI. Lastly, these patients help extend the phenotypic spectrum of Sotos syndrome to include HI as a significant feature.

Download full-text PDF

Source
http://dx.doi.org/10.1002/ajmg.a.61062DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6454923PMC
April 2019
35 Reads

Publication Analysis

Top Keywords

sotos syndrome
20
hyperinsulinemic hypoglycemia
12
nsd1 gene
8
nsd1 mutations
8
caused nsd1
8
5q35 deletions
8
hypoglycemia patients
8
nsd1
7
patients
6
syndrome
6
sotos
5
syndrome considered
4
cases 5q35
4
syndrome cases
4
considered patients
4
deletions patient
4
nsd1 mutation
4
intragenic nsd1
4
sufficient sotos
4
patient intragenic
4

References

(Supplied by CrossRef)
Hyperinsulinemic hypoglycemia in a patient with an intragenic NSD1 mutation
Carrasco Salas P. et al.
Am J Med Genet Part a 2016
Sotos syndrome
Cole T. R. et al.
Journal of Medical Genetics 1990
Sotos syndrome: A study of the diagnostic criteria and natural history
Cole T. R. et al.
Journal of Medical Genetics 1994
WHO child growth standards: Head circumference‐for age, arm circumference‐for‐age, tricepts skinfold‐for ‐age andsubscapular skinfold‐for‐age: Methods and development
Onis M. et al.
World Health Organization 2007
Identification of eight novel NSD1 mutations in Sotos syndrome
Kamimura J. et al.
Journal of Medical Genetics 2003
2000 CDC growth charts for the United States: Methods and development
Kuczmarski R. J. et al.
Vital and Health Statistics 2002
Sacrococcygeal Teratoma in two cases of Sotos syndrome
Leonard N. J. et al.
American Journal of Medical Genetics 2000

Similar Publications