RBBP8 syndrome with microcephaly, intellectual disability, short stature and brachydactyly

Area of Science:

• Genetics
• Developmental Biology
• Clinical Medicine

Background:

• Primary microcephaly is a heterogeneous neurodevelopmental disorder characterized by reduced head circumference.
• Genetic mutations, particularly in genes involved in DNA repair and cell cycle regulation, are known causes.
• RBBP8 mutations have previously been linked to distinct autosomal recessive microcephaly syndromes.

Observation:

• A consanguineous Pakistani family presented with multiple affected individuals.
• Clinical features included microcephaly, disproportionate short stature, brachydactyly, ectodermal defects (anonychia), and mild intellectual disability.
• Skeletal and limb anomalies, including talipes, were also observed in some patients.

Findings:

• Homozygous mutation c.1808_1809delTA (p.Ile603Lysfs*7) in the RBBP8 gene was identified in affected family members.
• This mutation expands the known phenotypic spectrum associated with RBBP8 mutations.
• The identified mutation leads to a distinct combination of congenital anomalies.

Implications:

• This finding highlights the genetic heterogeneity of primary microcephaly.
• Understanding the role of RBBP8 in development is crucial for diagnosing and potentially treating related disorders.
• Further research into RBBP8 function may uncover new therapeutic targets for neurodevelopmental conditions.