Endocrine Abstracts

JOINT1761

Background: Pseudohypoparathyroidism (PHP) and related disorders are a group of rare diseases associated with the phenotype known as Albright’s hereditary osteodystrophy (AHO), which includes round face, short stature, brachydactyly, ectopic ossifications, and intellectual disability. These conditions are caused by heterozygous inactivating mutations in the GNAS gene, leading to resistance to hormones acting via G protein-coupled receptors. The diagnosis is often delayed as the phenotypic features and hormonal resistance become apparent over time, with subtle manifestations in early childhood.

Case Presentation: We describe the case of a 9-year-old girl who was followed at the Endocrinology Department for stunted growth. Born at 32 weeks with intrauterine growth restriction, at the age of 2 years she was diagnosed with celiac disease and hypothyroidism with negative thyroid autoimmunity and normal gland position. The chromosomal microarray (CMA) did not reveal any genomic imbalances and the genetic testing for SHOX gene mutations was negative. She underwent surgery for right thumb paronychia with associated onychodystrophy at the age of 4. At the age of 5, idiopathic central precocious puberty was diagnosed, and pubertal suppression was initiated. At 7 years, her height relative to bone age was at -3 Standard Deviation Score while a disproportionate growth pattern and an abnormal shortening of the fourth metacarpal became apparent. At 8.5 years, she had a recurrent episode of paronychia affecting the foot. Skeletal X-rays showed dysmorphic features of metacarpals, metatarsals, and phalanges, along with ossifications in the soft tissues around the right big toe and the retrocalcaneal area on the left. These findings were consistent with skeletal dysplasia. Next-generation sequencing revealed a pathogenic de novo variant in the GNAS gene (c.1102_1125del, p.Asp368_Val375del) located in exon 13. Genetic analysis and radiological investigations ultimately revealed that the recurrent episodes of paronychia were, indeed, heterotopic ossifications, a hallmark feature of Albright hereditary osteodystrophy.

Conclusions: This case underscores the diagnostic challenges of PHP-related disorders in children, in which phenotypic features may be subtle or misinterpreted. Hypothyroidism, with a normally positioned thyroid gland, is one of the earliest signs, along with ectopic ossifications, which should be actively investigated, particularly in periarticular areas, hands, and plantar region. Additionally, even in syndromic short stature cases, precocious puberty can occur and mask the underlying condition. Awareness of AHO and its hallmark features, along with early genetic testing, are crucial for prompt diagnosis and timely management.