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Case Reports
. 2023 Jul 11;9(3):a006281.
doi: 10.1101/mcs.a006281. Print 2023 Jun.

FKBP14 kyphoscoliotic Ehlers-Danlos syndrome misdiagnosed as Larsen syndrome: a case report

Amy Wiegand  1 , Rama Kastury  2 , Arpita Neogi  3 , Arya Mani  3 , Allen Bale  4 , Allison Cox  4   5
Affiliations
Case Reports

FKBP14 kyphoscoliotic Ehlers-Danlos syndrome misdiagnosed as Larsen syndrome: a case report

Amy Wiegand et al. Cold Spring Harb Mol Case Stud. .

Abstract

Hereditary connective tissue disorders have overlapping phenotypes, particularly in regard to musculoskeletal features. This contributes to the challenge of phenotype-based clinical diagnoses. However, some hereditary connective tissue disorders have distinct cardiovascular manifestations that require early intervention and specific management. Molecular testing has increased the ability to categorize and diagnose distinct hereditary connective tissue disorders. A 42-yr-old female with a clinical diagnosis of Larsen syndrome from birth presented for genetic testing based on her recent diagnosis of premenopausal breast cancer. She had a past medical history of multiple carotid dissections. As she never had confirmatory molecular genetic testing for Larsen syndrome, whole-exome sequencing was utilized to assess both hereditary cancer predisposition syndromes and connective tissue disorders. A homozygous pathogenic variant in the FKBP14 gene was identified associated with FKBP14 kyphoscoliotic Ehlers-Danlos syndrome. We recommend that patients with a clinical diagnosis of Larsen syndrome undergo broad-based molecular sequencing for multiple hereditary connective tissue disorders. Molecular diagnosis is particularly crucial for all individuals who have a history of significant vascular events in the setting of a clinical diagnosis only. Early diagnosis of a hereditary connective tissue disorder with vascular features allows for screening and subsequent prevention of cardiovascular events.

Keywords: common carotid artery dissection; congenital kyphoscoliosis; generalized neonatal hypotonia.

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Figures

Figure 1.
Figure 1.
Computed tomography (CT) of the abdomen and pelvis with and without i.v. contrast of patient showing severe S-shaped scoliosis (left) and CT angiography (CTA) of the chest showing kyphoscoliosis.
Figure 2.
Figure 2.
Magnetic resonance angiography (MRA) of the neck with and without i.v. contrast of patient at age 40 showing severely tortuous internal carotid arteries
Figure 3.
Figure 3.
Overlapping major features of Larsen syndrome and FKBP14-kEDS. Features in bold represent clinical features seen in our case.
See this image and copyright information in PMC

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