ESPE Abstracts (2019) 92 P1-222

A Patient with a Novel Homozygous Mutation in IGF1-R Gene and Response to Growth Hormone Therapy

Al Shidhani Azza Nasser1, Adila Al-Kindi2, Irfan Ullah1, Hussein Al Saffar1, Saif Al Yaarubi1


1Pediatric Endocrine Unit,child health department, Sultan Qaboos University Hospital, Muscat, Oman. 2genetic department, Sultan Qaboos University, Muscat, Oman


Background: There are multiple factors affecting fetal growth, including maternal, fetal, placental and other environmental factors. Insulin like growth factor-1 ( IGF-1) has a major role in promoting fetal and post-natal growth. It is also proven that IGF1 promote brain, inner ear and retinal development.

Case: We report a 9-years old boy born at 31 weeks of gestation to a consanguineous parents by cesarean section for severe oligohydramnious and severe IUGR. At birth weight 1120g (-3.57SDS), length: 36cm (-4.64SDS) and Head Circumference: 26cm (-2.57SDS). He had dysmorphic features; cowlick thick hair, touch of synorphyrs small face, up-slating Palpebral fissure, infraorbital crease, hypertelorism, thin upper lip and dimple chin. Hands and feet: clinodactyl; little finger two phalanges only, single palmar crease and partial overriding toes on the left foot.

He was followed from early in life for failure to thrive, visual impairment and chronic constipation. Diagnosed with global developmental delay and recently with ADHD. IQ assessment at age of 5.5 years was 86.

Despite extensive investigation for the chronic constipation that started early in infancy, no cause was found. Subsequently it improved spontaneously.Teeth first erupted at the age of 2 years.

The routine screening for retinopathy of prematurity was negative. However, abnormal vascularization was noted at zone III in both fundi. On follow up, he was found to have small eyes with High hypermetropia and Flat cornea. Fundus exam and ERG confirmed the finding of retenitis pigmentosa and retina remained not completely vascularized with presence of retinal vessels in zone III.

He was referred to us for short stature at the age of 2 years where he was found to have high IGF1 and normal stimulated growth hormone peak.His short stature believed to be related to a syndromic cause at that stage. Other investigations showed normal brain auditory evoked potential and negative array CGH .

At age of 6-years, whole exome sequencing identified a novel homozygous mutation in IGF1R; NM_000875.4:c.431A>G (p.(Glu144Gly); which correlates very well with his phenotype. Segregation analysis done for both parents and healthy sibling showed all three are heterozygous of the same mutation.

At age of 6.5-years the child was started on growth hormone with a starting dose of ( 0.047mg/kg/dose six days in a week). His linear growth improved from -3 SD to – 2.3 SD 3 years after treatment.

Conclusion: The reported case represent the complicated role that IGF1 play in the human linear growth, brain and eye development.

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