hrp0095p1-103 | GH and IGFs | ESPE2022

A novel IGF1R variant in a child with mild IGF1 resistance, normal birth weight, mild short stature and microcephaly

Purushothaman Preetha , Gevers Evelien

Introduction: The insulin-like growth factor 1 receptor (IGF1R) gene, located on chromosome 15q26.3, encodes the 1367 aa tyrosine kinase receptor IGF1R which is involved in many processes, including growth. Few heterozygous mutations and deletions of IGF1R leading to IGF-I resistance have been described in patients with intrauterine and postnatal growth retardation, microcephaly and variable learning difficulties. We report a not yet previous...

hrp0086p2-p792 | Pituitary and Neuroendocrinology P2 | ESPE2016

Haplo-insufficiency for LHX4 Alone does not Result in Hypopituitarism

Kurre Mala , Gevers Evelien

Background: Two LIM homeodomain transcription factors, Lhx3 and Lhx4, are critical in the development of the nervous system and pituitary gland in mice. Lhx4 null mice die shortly after birth and have abnormal pituitary gland development. Recently, the first human homozygous LHX4 mutation was described, resulting in congenital hypopituitarism and neonatal death. Heterozygous LHX4 variants have been described and are linked to hypopituitarism but have...

hrp0094p2-299 | Growth and syndromes (to include Turner syndrome) | ESPE2021

Case report: Tall stature, obesity and hip dysplasia in Weaver syndrome due to a loss-of-function variant in EHZ2

Paraskevopoulou Niki , Gevers Evelien ,

Case report: We describe a male with tall stature (final height 210.5cm), macrocephaly (63.5cm, +5.5SD), obesity (BMI 44.6 kg/m2) and mild learning difficulties. Birth weight was 4.6kg (+2.3SD). He had slightly delayed developmental milestones. He was referred at the age of 5 for tall stature (+6.2SD), with a head circumference on the 98th centile, growing at a rate of 10cm/yr. He had thick doughy skin, a mild squint, somewhat coarse features, large hands...

hrp0095p1-429 | Bone, Growth Plate and Mineral Metabolism | ESPE2022

Progressive pseudorheumatoid dysplasia as a cause of short stature

Purushothaman Preetha , F Gevers Evelien

Introduction: Progressive pseudorheumatoid dysplasia (PPRD) is a rare genetic bone disorder characterised by the progressive degeneration of articular cartilage leading to pain, stiffness, joint enlargement and short stature. PPRD occurs due to a mutation in cellular communication network factor 6 (CCN6)/Wnt1-inducible signalling protein 3 (WISP3) gene, encoding a 354 amino acid signalling factor involved in BMP/WNT signalling and mitochondri...

hrp0097rfc10.1 | Fetal, neonatal endocrinology and metabolism (to include hypoglycaemia) & Multisystem endocrine disorders | ESPE2023

A novel maternally inherited GNAS variant in a family with hyperphagia and obesity.

Purushothaman Preetha , Ramakrishnan Anand , Gevers Evelien

Introduction: Heterozygous inactivating mutations in the maternal allele of the GNAS gene typically result in pseudohypoparathyroidism (PHP), characterised by developmental delay, short stature, obesity, hormone resistance and bone abnormalities. GNAS variants were recently described in 1% of patients in the UK Genetics of Obesity cohort, resulting in reduced MC4R signalling. Here, we report another novel GNAS variant in a family wit...

hrp0097p2-20 | Growth and Syndromes | ESPE2023

Temple Syndrome in monozygotic twins with GH and GnRHa treatment in one twin.

Lattanzi Claudia , Wilson Louise , Gevers Evelien

Temple syndrome is due to loss of methylation in the imprinted locus 14q32 and is characterised by low birth weight, hypotonia, short stature, early puberty. Adult height is approx -2.0SD. Other features are small hands and feet, premature birth, feeding difficulties, delayed milestones, mild learning difficulty, variable obesity. We report monozygotic twins diagnosed with Temple syndrome aged 13 yr. Twin 1 received GH for SGA and short stature from age 9.5yrs when his height ...

hrp0094p1-60 | Bone B | ESPE2021

Mosaic PHEX variants are important causes of X-linked hypophosphataemic rickets.

Prentice Philippa , Owens Martina , Brain Caroline , Allgrove Jeremy , Gevers Evelien ,

Introduction: X-linked hypophosphataemic rickets (XLH), due to mutations in the PHEX (Phosphate-regulating Endopeptidase homolog; X-linked) gene, causes reduced bone and dentin mineralisation and decreased renal phosphate reabsorption. Mosaic PHEX mutations are reported only in a few case reports.We report three male cases, with mosaic pathogenic PHEX variants, showing importance of considering this in the diagnosis of XLH.Case 1 pre...

hrp0094p2-16 | Adrenals and HPA Axis | ESPE2021

Rapid clearance of hydrocortisone as a cause of poor control of CAH detected by 24-hour profiling of hydrocortisone concentrations.

Iordanidou Aikaterini , Ong Ken , Hindmarsh Peter , Gevers Evelien ,

Introduction: Hydrocortisone (HC) has a short half-life and individualization of treatment is required for optimal treatment of CAH, balancing between under- and overtreatment. Twenty four hour profiling of HC concentrations has shown large interindividual variation in clearance of HC and therefore has been used to individualize treatment. We present a severely virialized girl with CAH, in whom high doses of steroids failed to suppress androgen production thou...

hrp0094p2-289 | Growth and syndromes (to include Turner syndrome) | ESPE2021

Familial Mosaic Turner Syndrome with short stature and spontaneous puberty due to a ring X chromosome with distal Xp22.3 and distal Xq26 deletion

Lim Sharon , Brain Caroline , Lees Melissa , Gevers Evelien ,

Abnormal phenotypes in patients with ring chromosome X can be ascribed to failed or partial X inactivation due to loss of XIST on Xq13. We describe a mother and 1 daughter with the same mosaic karyotype, and another daughter with 45, X. KZ, 12 years old and recently moved from Poland, was investigated for short stature (Ht SDS -2.1), her mother was 142.9 cm, father 176.1cm. Both were healthy and not dysmorphic. Birth weight at 37 weeks was 2.63kg (20th centile Polis...

hrp0097p2-18 | Growth and Syndromes | ESPE2023

Central precocious puberty in KBG syndrome due to a rare ANKRD11 variant

Blackburn James , Calder Alistair , Gaston-Massuet Carles , Gevers Evelien

Introduction: Establishing a clear diagnosis in patients with short stature can be challenging. Careful examination and investigation of patients with short stature may identify additional features that help to make a diagnosis or direct genetic testing. We describe a patient with severe short stature with additional features on examination suggestive of KBG syndrome. A subsequent skeletal survey revealed radiological features suggestive of the diagnosis. In a...