MAX-Related Disorder: Expanding the Phenotype of the Recurrent p.Arg60Gln Variant

Area of Science:

• Genetics
• Developmental Biology
• Clinical Medicine

Background:

• MAX gene mutations are associated with rare genetic disorders.
• Polydactyly and macrocephaly are key features of MAX-related disorder.
• Understanding the full spectrum of MAX-related disorder is crucial for diagnosis and management.

Observation:

• Two patients presented with four-limb postaxial polydactyly and a recurrent de novo MAX gene variant (c.179G>A).
• These patients exhibited previously reported features and novel clinical manifestations.
• Novel features included orofacial clefting, congenital heart defects, natal teeth, and sacrococcygeal teratoma.

Findings:

• The recurrent MAX c.179G>A (p.Arg60Gln) variant is confirmed as pathogenic.
• The phenotypic spectrum of polydactyly-macrocephaly syndrome/MAX-related disorder is significantly broadened.
• These findings represent the fifth and sixth known occurrences of this rare genetic condition.

Implications:

• Genetic testing is vital for patients with polydactyly and associated anomalies.
• Accurate genetic diagnosis aids in understanding disease progression and prognosis.
• Expanded knowledge of MAX-related disorder facilitates improved patient care and genetic counseling.