Familial scleroderma: nature, nurture or both?

Area of Science:

• Rheumatology
• Genetics
• Epidemiology

Background:

• Familial scleroderma (FS) risk factors, subtype concordance, and the relationship between age at onset (ASO) and date of onset (DSO) are not well understood.
• Investigating these factors is crucial for understanding scleroderma's complex etiology.

Purpose of the Study:

• To investigate familial scleroderma (FS) risk factors.
• To determine subtype concordance within families.
• To analyze the relationship between dates and ages at scleroderma onset.

Main Methods:

• Identified 47 cases across 23 families, including 25 familial scleroderma pairs.
• Defined scleroderma onset by Raynaud's phenomenon onset, first symptom onset (1SxO), second symptom onset (2SxO), and scleroderma diagnosis (SDx).

Main Results:

• Female predominance (8.4:1) and limited:diffuse ratios (3.3:1) were observed.
• Limited scleroderma showed a longer interval between Raynaud's onset and diagnosis (14.6 years vs. 3.1 years).
• Disease subtype concordance exceeded discordance, particularly in sister-sister and mother-daughter pairs. Younger family members were diagnosed at younger ages.
• Age at onset (ASO) differences between affected family members were 10-12 years, with closer ages for Raynaud's and 1SxO, and closer dates for 2SxO and SDx.

Conclusions:

• Familial scleroderma (FS) exhibits female predominance, a relatively late onset of Raynaud's phenomenon, and subtype ratios mirroring idiopathic scleroderma.
• Familial limited scleroderma has a longer prediagnostic latency compared to familial diffuse scleroderma.
• The findings suggest FS may be under-ascertained and that early symptoms (Raynaud's/1SxO) in familial limited scleroderma might be more genetically determined, while later events (2SxO/SDx) could be more influenced by environmental factors.