Table 4.

Disorders to Consider in the Differential Diagnosis of Cockayne Syndrome

Gene(s)DisorderMOIKey Feature(s) Overlapping w/CSDistinguishing Features
PLP1 Severe "connatal" Pelizaeus-Merzbacher disease (See PLP1 Disorders.) 1XLWhite matter abnormalities & growth restrictionSevere growth failure & distinctive physical appearance in CS
ATR
CPAP (CENPJ)
CEP152
CEP63
DNA2
NSMCE2
RBBP8 (CTIP)
TRAIP		Seckel syndrome (OMIM PS210600)ARProfound growth restrictionDistinctive physical appearance in CS
BRD4
HDAC8
NIPBL
RAD21
SMC1A
SMC3 		Cornelia de Lange syndrome AD
XL
CREBBP
EP300 		Rubinstein-Taybi syndrome AD
POLR3A Wiedemann-Rautenstrauch syndrome (OMIM 264090)AR
Genetically heterogeneous 2 Silver-Russell syndrome See footnote 2.
ANAPC1
RECQL4 		Rothmund-Thompson syndrome ARProminent photosensitivity &/or thinning of skin & hairWhite matter abnormalities, brain calcifications, ataxia, spasticity, & neurodegenerative features in CS
BLM Bloom syndrome AR
DDB2
ERCC1
ERCC2
ERCC3
ERCC4
ERCC5
POLH
XPA
XPC 		Xeroderma pigmentosum AR
LMNA Hutchinson-Gilford progeria syndrome AD
WRN Werner syndrome AR
>350 genes 3 Primary mitochondrial disorders AD
AR
Mat
XL		Early presence of pigmentary retinopathy, brain calcifications, & neurodegenerationSkin photosensitivity & distinctive physical appearance in CS
RAB3GAP1
RAB3GAP2
RAB18
TBC1D20 		RAB18 deficiency (molecular deficit underlying both Warburg micro syndrome & Martsolf syndrome)ARMicrocephaly, microcornea, & cataracts (RAB18 deficiency may resemble CS type II / COFS syndrome at birth)RAB18 deficiency is not assoc w/rapidly progressive neurodegeneration & has normal DNA nucleotide excision repair.
MORC2 MORC2-related disorder 4ADClinical presentation is very similar to CS in some persons & can incl microcephaly, growth restriction, & neurodevelopmental delays.Normal DNA nucleotide excision repair & no skin photosensitivity

AD = autosomal dominant; AR = autosomal recessive; COFS = cerebrooculofacioskeletal syndrome; CS = Cockayne syndrome; Mat = maternal; MOI = mode of inheritance; XL = X-linked

1.

Most leukodystrophies are not associated with growth restriction, with the exception of the severe or "connatal" form of Pelizaeus-Merzbacher disease, in which children may have short stature and poor weight gain.

2.

Genetic testing confirms clinical diagnosis in approximately 60% of affected individuals. Hypomethylation of the imprinted control region 1 (ICR1) at 11p15.5 causes Silver-Russell syndrome (SRS) in 35%-50% of individuals, and maternal uniparental disomy causes SRS in 7%-10% of individuals. Accurate assessment of SRS recurrence requires identification of the causative genetic mechanism in the proband.

3.
4.

From: Cockayne Syndrome

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