Abnormal brain iron accumulation is a rare finding in Down Syndrome Regression Disorder



      Down Syndrome Regression Disorder (DSRD) is characterized by the sudden loss of adaptive function, cognitive-executive function, language, with abnormal sleep and/or motor control.


      Clinical, laboratory and imaging data from 3 individuals with DSRD and iron on brain imaging were reviewed.


      Three patients with Down syndrome presented with new onset of flat affect, depression, reduced speech, and other neurologic symptoms consistent with DSRD. Magnetic resonance imaging showed abnormal iron accumulation in the basal ganglia, as well as calcification in 2 cases. Molecular diagnostic testing for NBIA was negative in the 2 individuals tested.


      These cases presented suggest a subset of individuals with DSRD have abnormal brain iron accumulation. Motor control symptoms reported in DSRD, such as stereotypies and parkinsonism, may reflect this basal ganglia involvement. The presence of abnormal brain iron should not delay or preclude diagnosis and treatment for DSRD.

      Key words

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'


      Subscribe to Pediatric Neurology
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Santoro J.D.
        • Partridge R.
        • Tanna R.
        • et al.
        Evidence of neuroinflammation and immunotherapy responsiveness in individuals with down syndrome regression disorder.
        J Neurodevel Disord. 2022; 14
        • Worley G.
        • Crissman B.G.
        • Cadogan E.
        • et al.
        Down syndrome disintegrative disorder: new-onset autistic regression, dementia, and insomnia in older children and adolescents with Down syndrome.
        J Child Neurol. 2015; 30: 1147-1152
        • Santoro S.L.
        • Cannon S.
        • Capone G.
        • et al.
        Unexplained regression in Down syndrome: 35 cases from an international Down syndrome database.
        Genet Med. 2020; 22: 767-776
        • Walpert M.
        • Zaman S.
        • Holland A.
        A systematic review of unexplained early regression in adolescents and adults with Down syndrome.
        Brain Sci. 2021; 11: 1197
        • Jacobs J.
        • Schwartz A.
        • McDougle C.J.
        • Skotko B.G.
        Rapid clinical deterioration in an individual with Down syndrome.
        Am J Med Genet. 2016; 170: 1899-1902
        • Akahoshi K.
        • Matsuda H.
        • Funahashi M.
        • et al.
        Acute neuropsychiatric disorders in adolescents and young adults with Down syndrome: Japanese case reports.
        Neuropsychiatr Dis Treat. 2012; 8: 339-345
        • Mircher C.
        • Cieuta-Walti C.
        • Marey I.
        • et al.
        Acute regression in young people with Down syndrome.
        Brain Sci. 2017; 7: 57
        • Ieshima A.
        • Kisa T.
        • Yoshino K.
        • et al.
        A morphometric CT study of Down’s syndrome showing small posterior fossa and calcification of the basal ganglia.
        Neuroradiology. 1984; 26: 493-498
        • Takashima S.
        • Becker L.
        Basal ganglia calcification in Down’s syndrome.
        J Neurol Neurosurg Psychiatry. 1985; 48: 61-64
        • Wisniewski K.E.
        • French J.H.
        • Rosen J.F.
        • et al.
        Basal ganglia calcification (BGC) in Down’s syndrome (DS)—another manifestation of premature aging.
        Ann N Y Acad Sci. 1982; 396: 179-189
        • Lee J.H.
        • Gregory A.
        • Hogarth P.
        • et al.
        Looking deep into the eye-of-the-tiger in pantothenate kinase-associated neurodegeneration.
        Am J Neuroradiol. 2018; 39: 583-588
        • Wu Y.W.
        • Hess C.P.
        • Singhal N.S.
        • et al.
        Idiopathic basal ganglia calcifications: an atypical presentation of PKAN.
        Pediatr Neurol. 2013; 49: 351-354
        • Sadana K.S.
        • Goraya J.S.
        Intracranial calcification in Down syndrome.
        J Pediatr Neurosci. 2018; 13: 120-121
        • Rosso M.
        • Fremion E.
        • Santoro S.
        • et al.
        Down syndrome disintegrative disorder: a clinical regression syndrome of increasing importance.
        Pediatrics. 2020; 145e20192939