Plantar keratoderma associated with developmental delay, intellectual impairment and abnormal facial features.  A possible new gene (FOXP1) association



We present a case of 17 year old adolescent with diffuse non-transgradient plantar keratoderma associated with plantar hyperhidrosis. He also suffers from intellectual disability, global developmental delay with speech and language impairment, fixed flexion deformity of fingers, tight calf muscles affecting gait, mitral regurgitation, facial abnormalities and history of recurrent infections. He has been diagnosed with a de novo heterozygous mutation in Forkhead Box Protein 1 (FOXP1) gene.
FOXP1 belongs to FOX gene family of transcription factor proteins that play an important role in in embryological, immunological, haematological and speech and language development.1,2 This is a rare condition with incidence limited to case reports only. There have been no reports of this mutation involving structures belonging to the ectodermal origin. FOXP1 mutation has been associated with developmental delay, intellectual disability, autism, speech and language development, joint contractures, cardiac abnormalities and abnormal facial features. To the best of our knowledge, this is the first case of FOXP1 mutation associated with plantar keratoderma. He does not have palmar keratoderma, or corneal involvement. However, there is abnormal dentition with crowding of teeth and along with keratoderma which raises possibility of FOXP1 having an influence on development of ectodermal lineage.
1. 1. Song et al. A case report of de novo missense FOXP1 mutation in a non-Caucasian patient with global developmental delay and severe speech impairment. Clinical Case Reports. 2015, 3(2):110-3.
2. 2. Horn D. Mild to moderate intellectual disability and significant speech and language deficit in patients with FOXP1 deletions and mutations. Mol Syndromol. 2011, 2:213-216.


Dr. Matthew Cho

Royal Adelaide Hospital

I am a second year trainee from South Australia, currently working at Royal Adelaide Hospital.