Fetal phenotypes in otopalatodigital spectrum disorders

Area of Science:

• Genetics
• Medical Genetics
• Skeletal Dysplasias

Background:

• Otopalatodigital spectrum disorders (OPDSD) encompass OPD syndrome types 1 and 2 (OPD1, OPD2), Melnick-Needles syndrome (MNS), and frontometaphyseal dysplasia (FMD).
• These disorders present with skeletal dysplasia and extra-skeletal anomalies, including brain, cardiac, and urogenital malformations.

Purpose of the Study:

• To investigate FLNA gene mutations in fetuses and a neonate with suspected OPDSD.
• To expand the understanding of the clinical and mutational spectrum of FLNA-related OPDSD.

Main Methods:

• FLNA gene analysis was performed on 10 fetuses and 1 neonate with multiple congenital anomalies suggestive of OPDSD.
• Clinical data and molecular findings were correlated.

Main Results:

• A global FLNA mutation rate of 44% was identified in the studied cohort.
• The findings expand the known clinical and mutational spectrum of FLNA in OPDSD.
• Clinical differentiation of OPDSD subtypes in fetuses is challenging due to overlapping features.

Conclusions:

• FLNA gene mutations are a significant cause of OPDSD, with a 44% detection rate in this series.
• Molecular analysis of FLNA is crucial for accurate diagnosis and refining genetic counseling in suspected OPDSD cases.
• Distinguishing OPDSD subtypes is important for providing precise genetic information to families.