Clinical Guidance

No clinically relevant genotype-phenotype correlations have been reported to date.

Source: GeneReviews — "PLOD1-Related Kyphoscoliotic Ehlers-Danlos Syndrome"

Penetrance

Penetrance for PLOD1-kEDS is 100%.

Source: GeneReviews — "PLOD1-Related Kyphoscoliotic Ehlers-Danlos Syndrome"

Diagnostic Criteria

Suggestive Findings

PLOD1-related kyphoscoliotic Ehlers-Danlos syndrome (PLOD1-kEDS) should be suspected in individuals with minimal criteria suggestive of PLOD1-kEDS.

Clinical Features

Major criteria

• Congenital muscular hypotonia

• Congenital or early-onset kyphoscoliosis (progressive or nonprogressive)

• Generalized joint hypermobility with dislocations/subluxations (shoulders, hips, and knees in particular)

Minor criteria

• Skin hyperextensibility

• Skin fragility (easy bruising, friable skin, poor wound healing, widened atrophic scarring)

• Rupture/aneurysm of a medium-sized artery

• Osteopenia/osteoporosis

• Blue sclerae, scleral and ocular fragility/rupture

• Hernia (umbilical or inguinal)

• Pectus deformity

• Marfanoid habitus

• Talipes equinovarus

• Refractive errors (myopia, hypermetropia)

• Microcornea

Source: GeneReviews — "PLOD1-Related Kyphoscoliotic Ehlers-Danlos Syndrome"

Differential Diagnosis

PLOD1-related kyphoscoliotic Ehlers-Danlos syndrome (PLOD1-kEDS) has some overlapping clinical features with other forms of Ehlers-Danlos syndrome (EDS), particularly classic EDS and vascular EDS. Abnormal wound healing and joint laxity are present in many EDS types. Although all types of EDS involve a relatively high risk for scoliosis compared to the general population, scoliosis in PLOD1-kEDS is usually more severe and of earlier onset than that seen in other EDS types. lists selected EDS-related genes and other genes of interest in the differential diagnosis of PLOD1-kEDS. Of note, all of the disorders in can be biochemically distinguished from PLOD1-kEDS by normal lysyl hydroxylase enzyme activity as indicated by the absence of a markedly increased ratio of deoxypyridinoline to pyridinoline cross-links in urine. Table 3. Selected Genes of Interest in the Differential Diagnosis of PLOD1-Related Kyphoscoliotic Ehlers-Danlos Syndrome

Management Guidelines

No clinical practice guidelines for PLOD1-related kyphoscoliotic Ehlers-Danlos syndrome (PLOD1-kEDS) have been published.

Evaluations Following Initial Diagnosis

To establish the extent of disease and needs in an individual diagnosed with PLOD1-kEDS, the evaluations summarized (if not performed as part of the evaluation that led to the diagnosis) are recommended.

Table 4.

PLOD1-Related Kyphoscoliotic Ehlers-Danlos Syndrome: Recommended Evaluations Following Initial Diagnosis

System/Concern | Evaluation | Comment

Neuromuscular

| PT eval to develop plan for ongoing therapy to strengthen large muscle groups prevent recurrent shoulder dislocation |

Musculoskeletal

| Eval for kyphoscoliosis incl photographs radiographs | Documentation is recommended in view of progressive kyphoscoliosis.

Referral to orthopedics for those w/clubfoot |

Skin | Consultation w/dermatologist to review skin findings discuss treatment of abnormal wound healing |

Cardiovascular

| Measurement of aortic root size assessment of heart valves by echocardiogram | At diagnosis or by age 5 yrs

Visualization of entire aorta w/CT or MRA | By young adulthood, or earlier if aortic or arterial dilatation is identified on echocardiogram

Eyes | Formal ophthalmologic eval for myopia, astigmatism, retinal detachment |

Hernia

| Referral to surgery for those needing hernia repair |

Genetic counseling

| By genetics professionals1 | To obtain a pedigree inform affected persons their families re nature, MOI, implications of PLOD1-kEDS to facilita...

Source: GeneReviews — "PLOD1-Related Kyphoscoliotic Ehlers-Danlos Syndrome"

Clinical Guidance

In children with significant joint hyperextensibility, sports that place stress on the joints (e.g., gymnastics, long-distance running) should be avoided. High-impact sports (collision sports), heavy lifting, and weight training with extreme lifting should be avoided. Arteriography should be discouraged and used only to identify life-threatening sources of bleeding prior to surgical intervention because of the risk of vascular injury.

Source: GeneReviews — "PLOD1-Related Kyphoscoliotic Ehlers-Danlos Syndrome"

Therapies Under Investigation

Search ClinicalTrials.gov in the US and EU Clinical Trials Register in Europe for information on clinical studies for a wide range of diseases and conditions. Note: There may not be clinical trials for this disorder.

Source: GeneReviews — "PLOD1-Related Kyphoscoliotic Ehlers-Danlos Syndrome"

Surveillance Guidelines

To monitor existing manifestations, the individual's response to supportive care, and the emergence of new manifestations, the evaluations summarized in are recommended. Table 6. PLOD1-Related Kyphoscoliotic Ehlers-Danlos Syndrome: Recommended Surveillance

Source: GeneReviews — "PLOD1-Related Kyphoscoliotic Ehlers-Danlos Syndrome"