Congenital Defect of the Skin of the New-Born

Sutton, Richard L.

doi:10.1001/archderm.1935.01460240080007

Cited by 20 publications

(2 citation statements)

References 2 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Since the description of scalp ACC centuries ago (3), it has remained a long-standing enigma why it occurs and, especially, why it is localized in most cases particularly at a defined anatomic site on the midline scalp without affecting other areas of the skin and without causing generalized skin and wound healing abnormalities in the adult. It has been postulated that ACC is the result of a primary defect in keratinocytes that results in their delayed migration or proliferation, leading to a skin closure defect of the rapidly expanding embryonic head where mechanical tension is particularly high (4)(5)(6). However, the molecular pathomechanisms and cellular origin of ACC remain unknown.…”

Section: Introductionmentioning

confidence: 99%

KCTD1/KCTD15 complexes control ectodermal and neural crest cell functions, and their impairment causes aplasia cutis

Raymundo,

Zhang,

Smaldone

et al. 2023

Journal of Clinical Investigation

View full text Add to dashboard Cite

Aplasia cutis congenita (ACC) is a congenital epidermal defect of the midline scalp and has been proposed to be due to a primary keratinocyte abnormality. Why it forms mainly at this anatomic site has remained a long-standing enigma. KCTD1 mutations cause ACC, ectodermal abnormalities, and kidney fibrosis, whereas KCTD15 mutations cause ACC and cardiac outflow tract abnormalities. Here, we found that KCTD1 and KCTD15 can form multimeric complexes and can compensate for each other’s loss and that disease mutations are dominant negative, resulting in lack of KCTD1/KCTD15 function. We demonstrated that KCTD15 is critical for cardiac outflow tract development, whereas KCTD1 regulates distal nephron function. Combined inactivation of KCTD1/KCTD15 in keratinocytes resulted in abnormal skin appendages but not in ACC. Instead, KCTD1/KCTD15 inactivation in neural crest cells resulted in ACC linked to midline skull defects, demonstrating that ACC is not caused by a primary defect in keratinocytes but is a secondary consequence of impaired cranial neural crest cells, giving rise to midline cranial suture cells that express keratinocyte-promoting growth factors. Our findings explain the clinical observations in patients with KCTD1 versus KCTD15 mutations, establish KCTD1/KCTD15 complexes as critical regulators of ectodermal and neural crest cell functions, and define ACC as a neurocristopathy.

show abstract