Report of two siblings with spondylodysplastic Ehlers-Danlos syndrome and B4GALT7 deficiency

Abstract Background The spondylodysplastic Ehlers-Danlos subtype (OMIM #130070) is a rare connective tissue disorder characterized by a combination of connective tissue symptoms, skeletal features and short stature. It is caused by variants in genes encoding for enzymes involved in the proteoglycan biosynthesis or for a zinc transporter. Presentation of cases We report two brothers with a similar phenotype of short stature, joint hypermobility, distinct craniofacial features, developmental delay and severe hypermetropia indicative for a spondylodysplastic Ehlers-Danlos subtype. One also suffered from a recurrent pneumothorax. Gene panel analysis identified two compound heterozygous variants in the B4GALT7 gene: c.641G > A and c.723 + 4A > G. B4GALT7 encodes for galactosyltransferase I, which is required for the initiation of glycosaminoglycan side chain synthesis of proteoglycans. Conclusions This is a first full report on two cases with spondylodysplastic Ehlers-Danlos syndrome and the c.723 + 4A > G variant of B4GALT7. The recurrent pneumothoraces observed in one case expand the variable phenotype of the syndrome.

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The Connective Tissue Disorder Associated with Recessive Variants in the SLC39A13 Zinc Transporter Gene (Spondylo-Dysplastic Ehlers–Danlos Syndrome Type 3): Insights from Four Novel Patients and Follow-Up on Two Original Cases

Genes ◽

10.3390/genes11040420 ◽

2020 ◽

Vol 11 (4) ◽

pp. 420 ◽

Cited By ~ 1

Author(s):

Camille Kumps ◽

Belinda Campos-Xavier ◽

Yvonne Hilhorst-Hofstee ◽

Carlo Marcelis ◽

Marius Kraenzlin ◽

...

Keyword(s):

Connective Tissue ◽

Short Stature ◽

Connective Tissue Disorder ◽

Zinc Transporter ◽

Facial Features ◽

Transporter Gene ◽

Ehlers Danlos Syndrome ◽

Type 3 ◽

Danlos Syndrome

Recessive loss-of-function variants in SLC39A13, a putative zinc transporter gene, were first associated with a connective tissue disorder that is now called “Ehlers–Danlos syndrome, spondylodysplastic form type 3” (SCD-EDS, OMIM 612350) in 2008. Nine individuals have been described. We describe here four additional affected individuals from three consanguineous families and the follow up of two of the original cases. In our series, cardinal findings included thin and finely wrinkled skin of the hands and feet, characteristic facial features with downslanting palpebral fissures, mild hypertelorism, prominent eyes with a paucity of periorbital fat, blueish sclerae, microdontia, or oligodontia, and—in contrast to most types of Ehlers–Danlos syndrome—significant short stature of childhood onset. Mild radiographic changes were observed, among which platyspondyly is a useful diagnostic feature. Two of our patients developed severe keratoconus, and two suffered from cerebrovascular accidents in their twenties, suggesting that there may be a vascular component to this condition. All patients tested had a significantly reduced ratio of the two collagen-derived crosslink derivates, pyridinoline-to-deoxypyridinoline, in urine, suggesting that this simple test is diagnostically useful. Additionally, analysis of the facial features of affected individuals by DeepGestalt technology confirmed their specificity and may be sufficient to suggest the diagnosis directly. Given that the clinical presentation in childhood consists mainly of short stature and characteristic facial features, the differential diagnosis is not necessarily that of a connective tissue disorder and therefore, we propose that SLC39A13 is included in gene panels designed to address dysmorphism and short stature. This approach may result in more efficient diagnosis.

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Novel mutation in the CHST14 gene causing musculocontractural type of Ehlers-Danlos syndrome

BMJ Case Reports ◽

10.1136/bcr-2018-226165 ◽

2018 ◽

pp. bcr-2018-226165 ◽

Cited By ~ 2

Author(s):

Sapna Sandal ◽

Anupriya Kaur ◽

Inusha Panigrahi

Keyword(s):

Connective Tissue ◽

Novel Mutation ◽

Connective Tissue Disorder ◽

Rare Disorder ◽

Compound Heterozygous Mutation ◽

Heterozygous Mutation ◽

Compound Heterozygous ◽

Bleeding Tendency ◽

Ehlers Danlos Syndrome ◽

Danlos Syndrome

Musculocontractural type of Ehlers-Danlos syndrome (MC-EDS) is a recently recognised connective tissue disorder. MC-EDS is caused by homozygous or compound heterozygous mutation in the carbohydrate sulfotransferase 14 (CHST14) gene on chromosome 15q15. Herein, we report a case of a 3-year-old boy with MC-EDS in whom a novel mutation in the CHST14 gene was discovered. Besides being the second report of this rare disorder from India, the child till 3 years has not had any bleeding tendency as described in the earlier reports of this disorder.

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Ehlers-Danlos Syndrome, Hypermobility Type: An Underdiagnosed Hereditary Connective Tissue Disorder with Mucocutaneous, Articular, and Systemic Manifestations

ISRN Dermatology ◽

10.5402/2012/751768 ◽

2012 ◽

Vol 2012 ◽

pp. 1-22 ◽

Cited By ~ 83

Author(s):

Marco Castori

Keyword(s):

Connective Tissue ◽

Correct Diagnosis ◽

Connective Tissue Disorder ◽

Joint Hypermobility ◽

Joint Hypermobility Syndrome ◽

Ehlers Danlos Syndrome ◽

Point Of Interest ◽

Wide Range ◽

Systemic Manifestations ◽

Danlos Syndrome

Ehlers-Danlos syndrome, hypermobility type, constituting a phenotypic continuum with or, perhaps, corresponding to the joint hypermobility syndrome (JHS/EDS-HT), is likely the most common, though the least recognized, heritable connective tissue disorder. Known for decades as a hereditary condition with predominant rheumatologic manifestations, it is now emerging as a multisystemic disorder with widespread manifestations. Nevertheless, the practitioners’ awareness of this condition is generally poor and most patients await years or, perhaps, decades before reaching the correct diagnosis. Among the various sites of disease manifestations, skin and mucosae represent a neglected organ where the dermatologist can easily spot diagnostic clues, which consistently integrate joint hypermobility and other orthopedic/neurologic manifestations at physical examination. In this paper, actual knowledge on JHS/EDS-HT is summarized in various sections. Particular attention has been posed on overlooked manifestations, including cutaneous, mucosal, and oropharyngeal features, and early diagnosis techniques, as a major point of interest for the practicing dermatologist. Actual research progresses on JH/EDS-HT envisage an unexpected link between heritable dysfunctions of the connective tissue and a wide range of functional somatic syndromes, most of them commonly diagnosed in the office of various specialists, comprising dermatologists.

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Gonosomal Mosaicism for a Novel COL5A1 Pathogenic Variant in Classic Ehlers-Danlos Syndrome

Genes ◽

10.3390/genes12121928 ◽

2021 ◽

Vol 12 (12) ◽

pp. 1928

Author(s):

Lucia Micale ◽

Thomas Foiadelli ◽

Federica Russo ◽

Luigia Cinque ◽

Francesco Bassanese ◽

...

Keyword(s):

Connective Tissue ◽

Sanger Sequencing ◽

Digital Pcr ◽

Connective Tissue Disorder ◽

Joint Hypermobility ◽

The Novel ◽

Ehlers Danlos Syndrome ◽

Targeted Ngs ◽

Next Generation Sequencing Ngs ◽

Danlos Syndrome

(1) Background: Classic Ehlers-Danlos syndrome (cEDS) is a heritable connective tissue disorder characterized by joint hypermobility and skin hyperextensibility with atrophic scarring. Many cEDS individuals carry variants in either the COL5A1 or COL5A2 genes. Mosaicism is relatively common in heritable connective tissue disorders but is rare in EDS. In cEDS, a single example of presumed gonosomal mosaicism for a COL5A1 variant has been published to date. (2) Methods: An 8-year-old girl with cEDS was analyzed by next-generation sequencing (NGS). Segregation was performed by Sanger sequencing in her unaffected parents. In the father, the mosaicism of the variant was further analyzed by targeted NGS and droplet digital PCR (ddPCR) in the blood and by Sanger sequencing in other tissues. (3) Results: The NGS analysis revealed the novel germline heterozygous COL5A1 c.1369G>T, p.(Glu457*) variant in the proband. Sanger chromatogram of the father’s blood specimen suggested the presence of a low-level mosaicism for the COL5A1 variant, which was confirmed by NGS and estimated to be 4.8% by ddPCR. The mosaicism was also confirmed by Sanger sequencing in the father’s saliva, hair bulbs and nails. (4) Conclusions: We described the second case of cEDS caused by paternal gonosomal mosaicism in COL5A1. Parental mosaicism could be an issue in cEDS and, therefore, considered for appropriate genetic counseling.

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Anesthetic Management of a Patient With Ehlers-Danlos Syndrome

Anesthesia Progress ◽

10.2344/16-00003.1 ◽

2016 ◽

Vol 63 (4) ◽

pp. 204-207 ◽

Cited By ~ 2

Author(s):

Naohiro Ohshita ◽

Masahiko Kanazumi ◽

Kaname Tsuji ◽

Hiroaki Yoshida ◽

Shosuke Morita ◽

...

Keyword(s):

Postoperative Pain ◽

Connective Tissue ◽

Anesthetic Management ◽

Synovial Chondromatosis ◽

Connective Tissue Disorder ◽

Joint Hypermobility ◽

Disease Type ◽

Clinical Feature ◽

Ehlers Danlos Syndrome ◽

Danlos Syndrome

We describe the case of a 37-year-old woman who had been diagnosed with Ehlers-Danlos syndrome (EDS) 4 years earlier and was scheduled to undergo removal of synovial chondromatosis in the temporomandibular joint. EDS is a heritable connective tissue disorder and has 6 types. In this case, the patient was classified into EDS hypermobility type. The major clinical feature of this type is joint hypermobility. The patient had sprain or subluxation of the elbows and ankles and dislocation of the knees. Anticipated problems during general anesthesia would be affected by the disease type. For this patient, extra attention was directed to positional injury–induced neuropathy and articular luxation, cutaneous injuries, injuries related to intubation and ventilation, and postoperative pain. Anesthesia was induced with propofol, remifentanil, and rocuronium and maintained with oxygen-air-desflurane, propofol, remifentanil, fentanyl, and rocuronium. In this case, the patient was safely managed without adverse events.

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Ehlers-Danlos syndrome presenting with primary nocturnal enuresis

BMJ Case Reports ◽

10.1136/bcr-2019-231977 ◽

2020 ◽

Vol 13 (2) ◽

pp. e231977

Author(s):

Margarida Cunha ◽

Mafalda Matias ◽

Inês Marques

Keyword(s):

Genetic Testing ◽

Nocturnal Enuresis ◽

Bladder Dysfunction ◽

Connective Tissue Disorder ◽

Joint Hypermobility ◽

Urinary Urgency ◽

Beighton Score ◽

Ehlers Danlos Syndrome ◽

Primary Nocturnal Enuresis ◽

Danlos Syndrome

Ehlers-Danlos syndrome (EDS), hypermobility type, is probably the most common EDS type, as well as the most common heritable connective tissue disorder. Bladder dysfunction is a rare clinical manifestation of EDS and manifests itself as primary nocturnal enuresis. We present a 10-year-old boy referred to the paediatrics nephrology consultation due to primary nocturnal enuresis and day time symptoms of urinary urgency. During the appointment, a tendency to joint hypermobility was noted. On evaluation the skin was hyperextensible and the Beighton score was positive. The genetic testing revealed a variant of the COL5A1 gene not yet described in the literature.

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