Clinical Challenges in Diagnosing Primordial Dwarfism: Insights from a MOPD II Case Study

Abstract

Background and Objectives.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. It is estimated that about 4 million infants die within the first month of life, with 99% of these deaths occurring in the neonatal period. Materials and Methods. Accurately diagnosing PD requires meticulous evaluation, as it can be easily confused with other genetic disorders that also cause dwarfism. In this article, we present the case of a 10-year-old patient diagnosed with MOPD II, the most common and well-documented form of microcephalic PD. Results. Genetic analysis revealed a pathogenic variant in the PCNT (pericentrin) gene ((c.1550dup, p.Gln518Alafs*7), alongside a deletion of exons 37-41. Conclusions. 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.

Keywords: MOPDII; PCNT gene; genetic variability; primordial dwarfism; rare disease.

Figure 1

The clinical findings in a 10-year-old male patient (A): Anterior view of the 10-year-old patient showing all body segments shortened symmetrically; (B,C): Frontal view of the patient’s face revealed an elongated face, mild prominence of the eye globes (slight maxillary protrusion), a small chin (micrognathia), and dental anomalies involving both position and size.

Figure 2

The patient exhibits significantly reduced growth velocity compared to his peers.

Figure 3

Radiological changes observed: widened, flared ‘champagne glass’ metaphyses with irregular contours in the forearm bones bilaterally. The radial and ulnar diaphyses are curved bilaterally. The left radius is shortened, with flared and irregular metaphyses in the distal phalanges and metacarpals.

Figure 4

Radiological changes observed in the pelvis and femora: the right acetabular cavity is flattened and vertically oriented. The femoral head nucleus on the right is not visible, and the right femur is elevated. The left acetabular cavity is slightly vertically oriented. The left femoral head nucleus is formed but irregular and fragmented. Bilateral femoral metaphyses are widened, flared, and irregular. Bilateral tibial metaphyses are also widened and flared.