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Updated: Jul 11, 2025
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Published on: May 8, 2020
Calloso-adreno-scrotal agenesis associated with biallelic MAPK-activating death domain protein (MADD) variant:
Sihem Darouich1,2, Samia Darouich3
1Faculté de Médecine de Tunis, Université de Tunis El Manar, Tunis, Tunisia.
Abstract:
MAPK-activating death domain protein (MADD) deficiency is associated with a broad clinical spectrum ranging from mild developmental impairment to fatal multisystem disorder. We report an additional case of severe form with some overlapping and unreported systemic features in a growth-restricted full-term male newborn. The novel findings include corpus callosum agenesis, bilateral adrenal agenesis, scrotal aplasia, and abnormal skin pigmentation. Microscopic changes are only remarkable in thyroid gland that shows decreased, variously sized follicles with absent or non-vacuolated pale colloid. This unique constellation of birth defects is associated with a novel homozygous in-frame MADD gene deletion (NM_003682.4: c.4853_4855delGCT:p.Cys1618del). This case report expands the phenotypic and genetic spectrum of MADD deficiency.
Insights
MAPK-activating death domain protein (MADD) deficiency presents a wide range of symptoms. This severe case in a newborn reveals novel features and a new MADD gene deletion, expanding understanding of the disorder.
Area of Science:
- Genetics
- Developmental Biology
- Endocrinology
Background:
- MAPK-activating death domain protein (MADD) deficiency is a rare genetic disorder with a variable clinical presentation.
- Previous reports describe a spectrum from mild developmental delays to severe, fatal multisystemic diseases.
Observation:
- A severe case of MADD deficiency in a growth-restricted male newborn is presented.
- This neonate exhibited previously unreported systemic features including corpus callosum agenesis, bilateral adrenal agenesis, scrotal aplasia, and abnormal skin pigmentation.
Findings:
- Microscopic examination revealed unique thyroid gland abnormalities with decreased follicular size and absent or pale colloid.
- Genetic analysis identified a novel homozygous in-frame deletion in the MADD gene (NM_003682.4: c.4853_4855delGCT:p.Cys1618del).
Implications:
- This case expands the known phenotypic spectrum of MADD deficiency, highlighting new congenital anomalies.
- The identification of a novel MADD gene deletion contributes to the understanding of genotype-phenotype correlations in this disorder.
- Further research is warranted to elucidate the precise mechanisms underlying the observed features and the role of MADD in development.
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