Table 3.

Selected Genes of Interest in the Differential Diagnosis of PLOD1-Related Kyphoscoliotic Ehlers-Danlos Syndrome

GeneDisorderMOIClinical Features of Disorder
Overlapping w/PLOD1-kEDSDistinguishing from PLOD1-kEDS
Other forms of Ehlers-Danlos syndrome (EDS)
AEBP1 Classical-like EDS type 2 (OMIM 618000)AR
  • Atrophic scarring, easy bruising
  • Joint hypermobility
  • Skin hyperextensibility
  • Prematurely aged appearance
  • Thinning of hair or (partial) alopecia
B3GALT6
B4GALT7
SLC39A13 		Spondylodysplastic EDS (spEDS) (OMIM 130070, 612350, 615349)AR
  • Joint hypermobility
  • Poor wound healing
  • Hypotonia
  • Skin hyperextensibility
Variable by related gene:
  • Progeroid characteristics
  • Vertebral dysplasia w/moderate short stature & characteristic features of the hands (thenar atrophy, short metacarpals & phalanges, inability to adduct thumbs)
CHST14
DSE 		Musculocontractural EDS
(OMIM 601776, 615539)		AR
  • Blue sclerae
  • Marfanoid habitus
  • Generalized joint hypermobility
  • Scoliosis
  • Skin hyperextensibility
  • Easy bruising; atrophic scarring
  • Hypotonia
  • Refractive errors
  • Characteristic facies
  • Adducted thumbs & feet 1
  • Gastrointestinal & genitourinary manifestations
COL3A1
(COL1A1) 2		Vascular EDS (vEDS)AD 3Vascular rupture (may be a feature of PLOD1-kEDS)
  • Intestinal rupture
  • Uterine rupture during pregnancy
COL5A1
COL5A2
(COL1A1) 4		Classic EDS (cEDS)AD
  • Atrophic scarring, easy bruising
  • Joint hypermobility
  • Skin hyperextensibility
  • Absence of congenital muscular hypotonia
  • Scoliosis rather than kyphoscoliosis
FKBP14 FKBP14-kEDS AR
  • Congenital muscular hypotonia
  • Congenital/early-onset kyphoscoliosis
  • Generalized joint hypermobility
  • Myopathy
  • Hearing loss
TNXB TNXB-related classical-like EDS (clEDS)AR
  • Easy bruising
  • Joint hypermobility
  • Skin hyperextensibility, velvety skin
Absence of atrophic scarring & kyphoscoliosis
Other disorders
PRDM5
ZNF469 		Brittle cornea syndrome (OMIM PS229200)AR
  • Corneal disorder
  • Skin hyperelasticity
  • Joint hypermobility
  • Thinning of cornea w/risk of rupture
  • Deafness (mixed conductive & sensorineural)

AD = autosomal dominant; AR = autosomal recessive; EDS = Ehlers-Danlos syndrome; MOI = mode of inheritance

1.
2.

Pathogenic variants in COL1A1 are listed as a rare cause of vEDS in the 2017 International Classification of the Ehlers-Danlos Syndromes [Malfait et al 2017].

3.

Vascular EDS is almost always inherited in an autosomal dominant manner, but rare examples of biallelic inheritance have been reported.

4.

The proportion of cEDS attributed to pathogenic variants in COL5A1 is 75%-78%; in COL5A2, 14%; and in COL1A1, <1%. The associated gene is unknown in ≤10% of individuals with cEDS.

From: PLOD1-Related Kyphoscoliotic Ehlers-Danlos Syndrome

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