Novel compound heterozygous mutations of PCNT gene in MOPD type II with central precocious puberty

Area of Science:

• Genetics
• Pediatrics
• Endocrinology

Background:

• Microcephalic Osteodysplastic Primordial Dwarfism type II (MOPD II) is a rare genetic disorder characterized by severe intrauterine and postnatal growth retardation, microcephaly, and distinct facial features.
• Genetic mutations in the PCNT gene are the primary cause of MOPD II.

Observation:

• A 6-year-old girl presented with short stature, microcephaly, a proboscis nose, small teeth, and underdeveloped secondary sexual characteristics (Tanner stage II).
• She exhibited intrauterine growth restriction (birth weight 800g at 37 weeks gestation) and postpartum growth defect.
• Nasopharyngeal adenoid hypertrophy and impaired glucose tolerance were also noted.

Findings:

• Genetic analysis identified two novel heterozygous mutations in the PCNT gene: c.1828dupT (p.S610Ffs*32) and a splice site mutation c.1207+1G>A.
• These mutations were inherited from her healthy carrier parents.
• Hormonal evaluation showed a normal growth hormone peak (>35.2 ng/ml) and luteinizing hormone peak (8.97 IU/l), suggesting central precocious puberty was not driven by pituitary dysfunction.

Implications:

• This case expands the known clinical spectrum of MOPD II, demonstrating its association with central precocious puberty and impaired glucose tolerance.
• Understanding these additional phenotypic manifestations is crucial for comprehensive diagnosis and management of MOPD II patients.
• Further research into the genotype-phenotype correlations of PCNT mutations may elucidate the mechanisms underlying these diverse clinical presentations.