The office said that Asma al-Assad, her three children as well as their cousins "took part Saturday in a charity event called... at the Damascus Opera House on the occasion of Mother's Day."
The event, dubbed 'Mothers Rally', was aimed at raising funds for the mothers of Syrian soldiers killed in fighting with rebels through the sale of crafts, the office said in a statement.
Assad's stylish British-born and British-educated wife is rarely seen in public, let alone with her three children -- two sons and a daughter.
In June last year Russia dismissed as "rumours" speculation on the Internet she had taken refuge in the country amid the escalating violence in Syria.
In January Assad's mother, Anisa Makhluf, reportedly left the war-torn country for Dubai to join her daughter Bushra, according to Syrian expatriates and an activist in the United Arab Emirates.
Bushra's husband General Assef Shawkat, an army deputy chief of staff, was killed along with three other high-ranking Syrian officials in a July 18, 2012 bombing at the National Security headquarters in Damascus.
The following September, Syrian residents in the Gulf emirate said that Bushra had enrolled her five children at a private school in Dubai where she had moved.