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Clinical Challenges in Diagnosing Primordial Dwarfism

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Primordial dwarfism (PD) is a rare group of genetic conditions where individuals experience severe growth restriction, both in the womb and after birth. From as early as the fetal stage, those affected are significantly smaller than their peers. What makes PD distinct is its slow but steady growth pattern, resulting in proportionate dwarfism, where all parts of the body are equally shortened. Diagnosing and managing PD presents significant challenges due to its rarity and the wide range of clinical and genetic variability. The main conditions in this group include Seckel syndrome, Microcephalic Osteodysplastic Primordial Dwarfism (MOPD) types I/III, MOPD type II, Meier-Gorlin syndrome, and Silver-Russell syndrome (SRS). The first four-Seckel syndrome, MOPD types I/III, MOPD type II, and Meier-Gorlin syndrome-are associated with microcephaly, and together they are known as microcephalic PD. Given how uncommon PD is, establishing its exact incidence is difficult.

Accurately diagnosing PD requires meticulous evaluation, as it can be easily confused with other genetic disorders that also cause dwarfism. In this article, the case of a 10-year-old patient diagnosed with MOPD II, the most common and well-documented form of microcephalic PD is presented.  Genetic analysis reveals a pathogenic variant in the PCNT (pericentrin) gene ((c.1550dup, p.Gln518Alafs*7), alongside a deletion of exons 37-41.

This case sheds light on the clinical and genetic complexities of primordial dwarfism, underscoring the importance of timely and accurate diagnosis for effective patient care. Read full article here.

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