Sophia Kalem Kim Dehling: Wrinkly Woman with Unique Genetic Syndrome
Meet Sophia Kalem Kim Dehling, a woman with dry, thin, wrinkled skin, looking older than her age, due to a rare genetic syndrome affecting collagen processing and vascular smooth muscle regulation. This case study explores her medical findings, variant search results, and the genetic mutations in ADAMTS2, ELN, and SACS genes. Clinical manifestations include skin hyperextensibility, tissue fragility, and various systemic features associated with Ehlers-Danlos syndrome and Cutis laxa. Discover the intricate genetic and clinical insights unraveling Sophia's condition.
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Presentation Transcript
CASE 1: A WRINKLY WOMAN SOPHIA KALEM KIM DEHLING
MEDICAL FINDINGS The patient has dry, thin, wrinkled skin, making her look much older than her actual age (33). Subcutaneous fat layer thinned out. Low muscle tone. Hair, nails and teeth normal. Cardiovascular evaluation by echocardiography revealed mitral valve prolapse and diffuse changes in myocardium. Ophthalmologic examination demonstrated exotropia and myopic astigmatism of both eyes. Intelligence normal. No family history of similar conditions. high-yield findings dry, thin, wrinkled skin older than her actual age low muscle tone mitral valve prolapse, diffuse changes in myocardium exotropia & myotic astigmatism intelligence normal no family history
SEARCH Total Variants: 15668 Filters used remove common (5022) remove silent (4978) exonic only (600) de novo only (43)
SELECTION Gene Affected Function ADAMTS2 ELN SACS Cleaves the propeptides of type I & II collagen, does not act on type III collagen Cleaves lysyl oxidase produce a short LOX form with reduced collagen- binding activity Major structural protein of tissues: aorta and nuchal ligament stabilizing arterial structure by regulating proliferation & organization of vascular smooth muscle Co-chaperone, acts as a regulator of the Hsp70 chaperone machinery may be involved in the processing of ataxia-linked proteins Expression Expressed at high level in skin, bone, tendon & aorta at low levels in thymus & brain Expressed within the outer myometrial smooth muscle & throughout the arteriolar tree of uterus expressed in the large arteries, lung & skin Highly expressed in the central nervous system found in skeletal muscle
SELECTION Clinical Manifestations dry, thin, wrinkled skin older than her actual age low muscle tone mitral valve prolapse, diffuse changes in myocardium exotropia & myotic astigmatism intelligence normal ADAMTS2 ELN SACS Ehlers-Danlos syndrome, dermatosparaxis type group of connective tissue disorder skin hyperextensibility articular hypermobility extreme skin fragility & easy bruising large fontanels blue sclerae puffy eyelids micrognathia (small chin) umbilical hernia short fingers Cutis laxa, autosomal dominant loose, hyperextensible skin with decreased resilience & elasticity premature aged appearance face, hands, feet, joints, & torso may be differentially affected Additional variable clinical features: gastrointestinal diverticula hernia genital prolapse Rare manifestations: pulmonary artery stenosis aortic aneurysm bronchiectasis emphysema Spastic ataxia Charlevoix-Saguenay type neurodegenerative disease early-onset cerebellar ataxia spasticity retinal hypermyelination axonal & demyelinating neuropathy with loss of sensory nerve conduction & reduced motor conduction velocity dysarthria distal muscle wasting nystagmus defect in conjugate pursuit ocular movements frequent presence of mitral valve prolapse
RESULT most probably Cutis Laxa due to prominent signs knock-out criteria: neurodegenerative disease Cutis Laxa: Ehler-Danlos:
