The disaster in Badakhshan province comes nearly a year after another landslide triggered by heavy rains buried a village in the isolated region, killing at least 300 people.
The disasters highlight the challenges facing underdeveloped Afghanistan as the country battles a resilient Taliban insurgency in what is expected to be the bloodiest spring-summer fighting season in a decade.
At least 25 women and 22 children were among those missing in the latest landslide in Jaryo Bala village of Badakhshan, deputy provincial governor Gul Mohammad Beidar said.
"We have asked Kabul for help and they have said they are sending two helicopters to assist with the rescue operations," Beidar told AFP.
"This is a remote area on the border with Tajikistan and the road to this district remains closed for six months of the year," he added, highlighting the challenges facing the relief effort.
Lal Mohammad Ahmadzai, the police spokesperson of Badakhshan, confirmed the toll.
"Initial information shows 100 houses have been destroyed in the landslide and 52 people are missing," Ahmadzai told AFP.
Flooding and landslides often occur during the spring rainy season in northern Afghanistan, with flimsy mud houses offering little protection against rising water levels and torrents of mud.
The landslide in May last year left hundreds of families homeless in Argu district of Badakhshan province which borders Tajikistan, China and Pakistan.
And last June flash floods killed around 80 people in a remote mountainous district of neighboring Baghlan province after heavy torrential rains.
Severe flooding also affected a vast swathe of Afghanistan last year, particularly Northern provinces, leaving 175 people dead and tens of thousands displaced.
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