[Microcephalic osteodysplastic primary dwarfism type II with hypergonadotropic hypogonadism in a 16-year-old patient]

Area of Science:

• Genetics
• Endocrinology
• Neurology

Background:

• Microcephalic osteodysplastic primary dwarfism type II (MOPDII) is a rare primordial dwarfism syndrome.
• It is characterized by severe growth retardation, microcephaly, skeletal dysplasia, and metabolic and neurovascular issues.
• Seckel syndrome is a related condition with overlapping features.

Purpose of the Study:

• To describe a patient with MOPDII and Seckel syndrome phenotype.
• To identify the genetic cause of the condition.
• To document novel clinical manifestations, including neurovascular and endocrine abnormalities.

Main Methods:

• Clinical phenotyping and detailed medical history.
• Biochemical testing for carbohydrate metabolism (including Matsuda index).
• Clinical exome sequencing to identify genetic variants in the PCNT gene.

Main Results:

• The patient presented with MOPDII and Seckel syndrome features, including internal carotid artery aneurysms, intracerebral hemorrhages, hypertension, diabetes mellitus, and thrombocytosis.
• Genetic analysis revealed two rare heterozygous variants (c.6220C>T and c.4564-12T>A) in the PCNT gene, confirming the MOPDII diagnosis.
• Metformin therapy improved carbohydrate metabolism, and hypergonadotropic hypogonadism was observed for the first time in this syndrome.

Conclusions:

• The study confirms the diagnosis of MOPDII in a patient with a Seckel syndrome phenotype.
• Novel neurovascular and endocrine complications, including hypergonadotropic hypogonadism, are reported in MOPDII.
• Genetic variants in the PCNT gene are associated with this complex phenotype, underscoring the importance of molecular diagnostics.