Growth pattern of Rahman syndrome

Area of Science:

• Genetics
• Developmental Biology
• Human Physiology

Background:

• Intellectual disability and overgrowth syndromes are complex genetic disorders.
• HIST1H1E gene variants have been recently associated with overgrowth syndrome and intellectual disability.
• The growth patterns in individuals with HIST1H1E variants require further clarification.

Observation:

• A female patient presented with intellectual disability, distinctive facial features, and short stature, not skeletal overgrowth.
• Exome analysis revealed a de novo heterozygous duplication in HIST1H1E (c.433dup p.(Ala145Glyfs*51)).
• Physical features were consistent with previously reported HIST1H1E-related overgrowth syndrome.

Findings:

• A review of seven patients indicated that five did not exhibit skeletal overgrowth.
• Growth trajectories showed complexity, with some patients having decreasing height percentiles over time.
• The study identified a novel HIST1H1E mutation in a patient with short stature and intellectual disability.

Implications:

• The findings challenge the classification of HIST1H1E-related disorders solely as overgrowth syndromes.
• The condition, characterized by variable growth patterns, is proposed to be named Rahman syndrome.
• This research highlights the need to reconsider growth parameters in diagnosing genetic syndromes.