Biallelic MADD variants cause a phenotypic spectrum ranging from developmental delay to a multisystem disorder
A new study published in Brain identified 23 patients with 21 different pathogenic MADD variants identified by next-generation sequencing. 14 patients presented with severe developmental delay, endo- and exocrine dysfunction, impairment of the sensory and autonomic nervous system, and haematological anomalies. Nine patients had a predominant neurological phenotype comprising mild-to-severe developmental delay, hypotonia, speech impairment, and seizures. This study showed that MADD deficiency underlies multiple cellular defects that can be attributed to alterations of TNF-α-dependent signalling pathways and defects in vesicular trafficking.
- Brain . 2020 Aug 1;143(8):2437-2453