Hand and foot malformations

Gene: SMC1A

Green List (high evidence)

Cornelia de Lange syndrome is a clinically heterogeneous developmental disorder characterized by malformations affecting multiple systems. Affected individuals have dysmorphic facial features, cleft palate, distal limb defects, growth retardation, and developmental delay. About 4 to 6% of patients have mutations in the X-linked SMC1A gene (numerous cases reported).

Multiple females reported with EE/HPE and LOF variants in this gene.

Created: 19 Aug 2021, 9:03 a.m. | Last Modified: 19 Aug 2021, 9:03 a.m.

Panel Version: 0.8886

Mode of inheritance
X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)

Phenotypes
Cornelia de Lange syndrome 2, MIM# 300590; Epileptic encephalopathy, early infantile, 85, with or without midline brain defects, MIM# 301044

Publications

• 29023665
• 31409060
• 31334757
• 28166369

Green List (high evidence)

SMC1A truncation mutations are seen only in females and cause a condition in which the typical features of CdLS are often absent. These patients are affected by moderate to severe developmental impairment and drug-resistant epilepsy.
Loss of function and dominant negative have both been reported as disease mechanisms.

Created: 3 Mar 2020, 12:53 a.m. | Last Modified: 3 Mar 2020, 12:53 a.m.

Panel Version: 0.1590

Mode of inheritance
X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)

Phenotypes
Cornelia de Lange syndrome 2 300590

Publications

• 17273969
• 22106055
• 19701948
• 26752331
• 28166369