Conditions Associated with Palmar Crease and Abnormal Chromosome Microarray
The most clinically significant condition presenting with a single transverse palmar crease (simian crease) and abnormal chromosome microarray is Down syndrome (Trisomy 21), though multiple other chromosomal abnormalities and genetic syndromes can present with this combination of findings. 1
Primary Chromosomal Abnormalities
Down syndrome (Trisomy 21) is the classic association with simian crease and will show aneuploidy on chromosome microarray analysis. 1 The prenatal detection of simian crease should prompt immediate consideration of trisomy 21, as this represents the most common chromosomal abnormality associated with this palmar finding.
Other Chromosomal Conditions
While Down syndrome is most common, other constitutional cytogenetic abnormalities detectable by microarray include:
- Aneuploidy (extra or missing chromosomes) - Microarray can detect these copy number changes 2
- Structural aberrations including deletions, duplications, and marker chromosomes that result in unbalanced chromosomal material 2
- Submicroscopic chromosomal abnormalities not visible on standard karyotype but detectable at 50-100 kb resolution 3
Non-Chromosomal Genetic Syndromes
DOORS syndrome (Deafness, Onychodystrophy, Osteodystrophy, Mental Retardation, and Seizures) presents with single transverse palmar creases bilaterally and is caused by mutations in the TBC1D24 gene. 4 While this is a single-gene disorder, chromosome microarray may be performed as part of the diagnostic workup for the multiple congenital anomalies, though the specific mutation requires targeted gene sequencing for diagnosis.
Structural Malformations with Chromosomal Associations
Simian creases have been documented in fetuses with:
These conditions may have normal chromosomes but warrant microarray analysis given the presence of multiple congenital anomalies. 3
Diagnostic Approach
When encountering a patient with a palmar crease abnormality, chromosome microarray should be the first-line genetic test for detecting copy number variations, as recommended by the American College of Medical Genetics for individuals with developmental delays or multiple anomalies. 3
Key Testing Considerations:
- Microarray detects unbalanced chromosomal abnormalities including deletions and duplications with superior resolution (50-100 kb) compared to karyotyping (5-10 Mb) 3
- Microarray has a diagnostic yield of approximately 10% in children with developmental delays versus 3.7% for karyotyping 3
- Microarray cannot detect balanced rearrangements - if family history suggests balanced translocation, karyotyping is required 2, 3
- Low-level mosaicism below 20-30% may not be reliably detected by microarray 3
When Microarray is Abnormal:
Parental testing should be performed when abnormalities are identified to distinguish between de novo pathogenic variants and inherited familial variants. 2 This is critical for determining clinical significance and recurrence risk.
When Microarray is Normal:
If clinical suspicion remains high despite normal microarray:
- Consider targeted gene sequencing for specific syndromes like DOORS syndrome 3
- Consider karyotyping if balanced rearrangements are suspected based on family history 3
- Traditional karyotyping may be more sensitive for detecting low-level sex chromosome mosaicism 3
Important Clinical Pitfalls
Do not assume all palmar crease variants indicate pathology - approximately 10% of the normal Caucasian population has variant palmar creases, and these can be familial. 5, 6 The presence of simian crease alone without other clinical findings has limited diagnostic significance.
The combination of palmar crease abnormality with other dysmorphic features, developmental delay, or congenital anomalies significantly increases the likelihood of an underlying chromosomal abnormality and warrants comprehensive genetic evaluation. 1, 4, 7
Microarray analysis will not detect point mutations in single genes - if a specific monogenic syndrome is suspected (like DOORS syndrome), targeted gene sequencing or exome sequencing is required. 2, 3