Features include very common findings: EEG abnormality, Motor delay, and Delayed speech and language development; and common findings: Delayed CNS myelination, Seizure, Decreased heart rate variability, and Chronic constipation and others. 49 total HPO annotations.

MADD encodes MAP kinase activating death domain (1,647 aa). Guanyl-nucleotide exchange factor that regulates small GTPases of the Rab family. Converts GDP-bound inactive form of RAB27A and RAB27B to the GTP-bound active forms. Highest expression in Brain Cerebellum (173.2 TPM) and Brain Cerebellar Hemisphere (169.2 TPM).

Neurodevelopmental disorder with dysmorphic facies, impaired speech, and hypotonia is associated with mutations in the MADD gene on chromosome 11.

The MADD protein participates in MADD exchanges GTP for GDP on RAB27, SLC52A1,2,3 transport RIB from extracellular region to cytosol, and RAB3 GEFs exchange GTP for GDP on RAB3A pathways.

MADD is classified as a druggable target (Kinase and Tumor Suppressor categories) with score 0.0.

Genetic testing for MADD is available. Testing is considered confirmatory for diagnosis.

Phenotype severity distribution: 3 very common features, 10 common features.

No clinical trials have been registered for neurodevelopmental disorder with dysmorphic facies, impaired speech, and hypotonia.

1 publication has been identified in PubMed for neurodevelopmental disorder with dysmorphic facies, impaired speech, and hypotonia. Research spans Case Report / Case Series (100%).

Recent Publications

• Cohen R (2026). [PMID: 41311105](https://pubmed.ncbi.nlm.nih.gov/41311105/). *Am J Med Genet A*. [Case Report / Case Series]