A New Case with Weaver Syndrome: Delineating Natural Course and Growth Pattern, Further Clarifying Clinical Phenotype.

Abstract

Introduction: Weaver syndrome, rare syndromic cause of tall stature, presents with overgrowth, accelerated skeletal maturation, dysmorphic features, and camptodactly. Despite expanding knowledge and widespread use of genetic tests, differential diagnosis of tall statue may be challenging, complicating follow-up. Here we describe a patient with a variant in EZH2, underlining presenting features and natural course.

Case presentation: Twenty-month-old girl consulted for tall stature was born at term (birthweight: 2,600 g [-0.8 SDS], birth length: 54 cm [2.4 SDS]) as the third child of non-consanguineous parents. Without any other complaints, she was 15.2 kg (2.5 SDS) and her height was 95 cm (3.1 SDS). She was proportionately tall compared to her parents (target height: 156 cm [-1.1 SDS]). Endocrine evaluation did not reveal pathology, growth traced parallel to 97th percentile of growth curve. Karyotype analysis and fibrillin gene analysis were normal. As she had mild intellectual disability and minor dysmorphic features (broad forehead, mild hypertelorism, long philtrum, thin upper lip and a prominent chin dimple, bilateral camptodactyly), whole exome analysis including copy number variant changes that revealed a heterozygous variant on EZH2 was performed when she was 14 years old. Weaver syndrome was diagnosed.

Conclusion: Tall stature, height SDS exceeding target height SDS, tall stature at birth, normal growth rate, minor dysmorphic features, and mild intellectual disability should prompt syndromic etiology of tall stature. Further genetic analysis should be implemented. Diagnosis of rare syndromes is crucial for defining prognosis, organ involvement, and natural course, avoiding unnecessary endocrine investigations.