Genotype-endocrine phenotype associations in a large cohort of children with NF1

Robyn Haysom; Wright Emma Burkitt; Sameera Auckburally; Zulf Mughal; Peter Clayton; Raja Padidela; Amish Chinoy

doi:10.1530/endoabs.111.OC8.2

OC8.2

Prev Next

Section Contents Cite

Endocrine Abstracts (2025) 111 OC8.2 | DOI: 10.1530/endoabs.111.OC8.2

BSPED2025 Oral Communications Endocrine Oral Communications 3 (5 abstracts)

Genotype-endocrine phenotype associations in a large cohort of children with NF1

Robyn Haysom ^1,2 , Emma Burkitt Wright ³ , Sameera Auckburally ⁴ , Zulf Mughal ⁵ , Peter Clayton ¹ , Raja Padidela ^1,4 & Amish Chinoy ⁴

Author affiliations

¹University of Manchester, Manchester, United Kingdom; ²University Hospitals of North Midlands, Stoke-on-Trent, United Kingdom; ³St Mary’s Hospital, Manchester, United Kingdom; ⁴Royal Manchester Children’s Hosptial, Manchester, United Kingdom; ⁵Al-Jalila Hospital, Dubai, UAE

Introduction: NF1 is an autosomal dominant condition affecting 1 in 2500 births and can be associated with short stature and macrocephaly. Although genotype-phenotype associations have been studied for other phenotypes of NF1, endocrine phenotypes have never been previously explored.

Methods: Retrospective data analysis was conducted in children with NF1 known to a quaternary centre. Data on demographics, pubertal status, height, weight, body mass index (BMI) and head circumference (HC) was recorded, with the latter measurements converted into standard deviation scores (SDS). Data on mutation type was collected and grouped accordingly: frameshift, nonsense, missense, intronic, miscellaneous intragenic and whole gene deletions.

Results: 201 patients (97 girls, mean age 10.0 years) were included. Table 1 demonstrates the mean height, weight, BMI and OFC SDS by mutation type, with no significant difference generally between groups on ANCOVA analysis, except with BMI SDS. Independent T-test comparing the whole gene deletion to other types of mutations demonstrated significantly taller stature (P = 0.027), greater weight (P = 0.020) and greater BMI (P = 0.022). Pubertal issues (precocious or delayed) were only observed in those with frameshift (10.2%), nonsense (8.2%) or intronic (7.1%) mutations.

Table 1
		Frameshift	Nonsense	Missense	Intronic	Misc intragenic	Whole gene deletion	p-value
Height SDS	Mean	-0.8	-0.8	-0.8	-0.7	-0.8	-0.2	0.57
	SD	1.3	1.1	1.4	1.4	1.6	1.02
Weight SDS	Mean	-2.0	-0.2	-0.6	-0.1	0.5	0.8	0.13
	SD	2.3	1.4	1.4	1.2	1.2	1.5
BMI SDS	Mean	0.2	0.3	0.0	0.4	1.2	1.04	0.045
	SD	1.2	1.5	1.2	1.2	0.9	1.3
HC SDS	Mean	0.7	1.3	0.8	1.3	1.1	0.7	0.45
	SD	1.3	1.7	1.7	1.3	0.7	1.5

Conclusion: Similar growth phenotypes are observed across mutation types, with the exception of whole gene deletions, due to a gene within the microdeletion whose haploinsufficiency may cause overgrowth, which has been suggested previously. The variability in BMI SDS observed may be due to genuine but non-significant differences in height and weight SDS between other groups, which warrants further work with larger groups.