Skip to main content
Erschienen in: BMC Pediatrics 1/2021

Open Access 01.12.2021 | Case report

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

verfasst von: Delia Lorenz, Wolfram Kress, Ann-Kathrin Zaum, Christian P. Speer, Helge Hebestreit

Erschienen in: BMC Pediatrics | Ausgabe 1/2021

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.
Hinweise

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Abkürzungen
EDS
Ehlers-Danlos syndrome
LRS
Larson La Reunion syndrome

Background

The Ehlers-Danlos syndromes (EDS) are a large heterogeneous group of heritable connective tissue disorders. The 2017 classification regrouped the EDS into six groups (A to F) according to underlying genetic and pathogenic mechanisms [1]. While the classical EDS is part of the disease group A in which collagen structure and collagen processing is affected resulting in the main clinical features of skin hyperextensibility and joint hypermobility, EDS entities of other genetic / pathogenic groups have a wider phenotypic variability.
The EDS spondylodysplastic type (group D: disorders of glycosaminoglycan biosynthesis) is either caused by homozygous or compound heterozygous mutations in the B4GALT7 gene on chromosome 5q35, or by mutations in the B3GALT6 gene (galactosytransferases) (OMIM # 615349) or in the SLC39A13 gene (zinc transporter) (OMIM # 612350) [2, 3]. It is inherited in an autosomal recessive pattern. The phenotype is defined by short stature and generalized muscular hypotonia as major criteria, and skin hyperextensibility, soft doughy skin, pes planus, delayed motor and cognitive development and osteopenia as minor criteria. There are also gene-specific minor criteria such as severe hypermetropia, characteristic craniofacial features, bilateral elbow contractures and radiographic findings, e.g. radioulnar synostosis for B4GALT7 enzyme deficiency.
The B4GALT7 protein is a member of the beta-1,4-galactosyltransferase family and is involved in the formation of the glycosaminoglycan-protein bond in proteoglycans. The enzyme encoded by this gene attaches the first galactose in the common carbohydrate-protein linkage found in proteoglycans. Defective structures or deficient quantities of this enzyme lead to insufficient amounts of mature functional proteoglycans [4, 5] .
We describe two siblings who are compound heterozygous for variants in the B4GALT7 gene – the splice variant (c.723 + 4A > G) described provisionally [6] and the missense variant previously reported in mutation databases (e.g. HGMD: CM166199, ClinVar: RCV000239469.1604327.007, OMIM #604327.007) - further confirming the variable phenotypic spectrum associated with pathogenic variants in this gene.

Presentation of cases

The two brothers (18 and 15y) were patients in our neuropediatric department since 2003 and were later seen in the Center for Rare Diseases. The parents and patients gave consent for genetic analysis and publication.
Clinical description.
Patient 1 (male, 18 years): Pregnancy and delivery at term were normal, as were the anthropometric measures at birth (Table 1). Hypothyroidism was diagnosed at the age of 6 months and severe hypermetropia at the age of 3 years. Additional symptoms reported at the age of 5.4 years were delayed (fine) motor development and short stature. Clinical follow up at 9.4 years revealed delayed cognitive development, flat, skew feet and a hoarse voice. From the age of 15 to 17 years, the patient suffered from recurrent spontaneous pneumothoraces that were finally treated by pleurectomy and pleurodesis. Furthermore, he presented with several patellar luxations. Clinical examination at the age of 18 years showed short stature with a relatively large head, joint hypermobility, and distinct craniofacial features (big eyes, thin lips and small mouth, deep set ears).
Table 1
Summary of patients’ symptoms
  
Patient 1
(18 years)
Patient 2
(15 years)
Gestational age
 
40 weeks
41 weeks
Anthropometry at birth
Height
48 cm (3rd centile)
51 cm (10th centile)
 
Weight
3310 g (25th centile)
3160 g (10th to 25th centile)
Anthropometry
Height
156.5 cm (3 cm <3rd centile)
148.5 cm (6 cm <3rd centile)
 
Weight
68.2 kg (50th centile)
49.2 kg (10. centile)
 
Head circumference
59 cm (90th centile)
57.5 cm (75th to 90th centile)
Development
Motor
Delayed
Delayed
 
Speech
Delayed
 
Cognitive
Delayed
 
Craniofacial features
 
Big eyes, thin lips, deep set ears
Thin lips, prominent forehead
Musculoscelettal
 
Joint hypermobility
Joint hypermobility
  
Flat, skew feet
Flat, skew feet, crossing of 2nd and 3rd toe
   
Scoliosis
Eyes
 
Severe hypermetropia
Severe hypermetropia
Other
 
Hypothyroidism
Hypothyroidism
  
Recurrent pneumothoraces
 
  
Patellar luxations
 
  
Hoarse voice
 
Patient 2 (male, 15 years): No complications occurred during pregnancy and delivery, length and weight at birth were normal (Table 1). Hypothyroidism was diagnosed at the age of 4 months. The boy was seen again at the age of 2.2 years, when he presented with developmental delay (free walking started at the age of 2.1 years, word pool of approximately 20 words), short stature, and severe hypermetropia. At the age of 5.0 years and 6.3 years, additional diagnoses comprised nutritional problems, speech developmental disorder, and flat, skew feet. Clinical examination at age 15 years showed persistent short stature and low weight, scoliosis, joint hypermobility, distinct craniofacial features (small lips, prominent forehead), and crossing of 2nd and 3rd toes.
The non-consanguineous parents came from Romania. There was no family history for short stature, joint hyperextensibility, skin laxity or dysmorphic features.

Radiographic features

Within the diagnostic work-up for small stature, hand and wrist radiographs were taken in both brothers. They revealed an accelerated bone development of approximately 2y in patient 1 and a slightly accelerated bone development in patient 2 (Fig. 1a–d). Due to recurrent pneumothoraces, 37 chest X-rays (Fig. 2a, b) were taken of patient 1, and one X-ray of the right knee because of recurrent patellar luxations (Fig. 2c). X-rays showed no signs of osteopenia.

Genetic analysis

Previous genetic evaluation in patient 1 included a chromosomal analysis at age 6 years and an array-CGH at age 14 years with normal results. An Ehlers-Danlos syndrome with its various subtypes was considered. Therefore, NGS panel analysis (TruSight One (Illumina, San Diego, CA USA)) was done for both brothers to identify their shared disease-causing variants. Targeted enrichment was performed by Nextera Rapid Capture from genomic DNA according to manufacturer’s protocols and sequencing was done on a NextSeq500 desktop sequencer (Illumina). Sequence coverage was at average 123x for the analyzed genes. Raw data (fastQ) were aligned to the human reference genome (GRCh37) using an integrated aligner in GensearchNGS (PhenoSystems SA, Wallonia, Belgium). This software was also applied for variant calling, visualization and filtering of variants. Variants were filtered according to the following criteria: variant frequency greater than 25%, minor allele frequency below 1%, occurrence in both brothers. Classification of variants was performed according to American College of Medical Genetics and Genomics (ACMG) guidelines [7] using Alamut Visual (Interactive Biosoftware, Rouen, France) including incorporated tools and databases. Sanger sequencing was done using routine protocols on an ABI3730 sequencing machine (Applied Biosystems, Foster City, USA).

Results

Gene panel analysis revealed compound heterozygous variants in the B4GALT7 gene, c.723 + 4A > G in Intron 4 and c.641G > A in exon 4 in both brothers. The parents were each heterozygous for one of the variants identified. The c.723 + 4A > G variant was inherited from the mother and the c.641G > A variant was inherited from the father. The variant c.641G > A (p.C214Y) is a known disease-causing variant that has been published before in a patient with EDS in compound heterozygous state with a known pathogenic variant (PM3, PP5 according to ACMG criteria) [8]. Additionally, the variant is very rare as annotated in gnomAD browser [9] (PM2), predicted to be pathogenic by in silico tools (e.g. PolyPhen2 [10], MutationTaster [11] (PP3)) and was found in the catalytic domain of the protein (PM1). Therefore, the variant was classified as likely pathogenic according to ACMG guidelines. The splice variant c.723 + 4A > G has been described once before in a presentation at the Variant Effect Prediction Training Course (VEPTC) [6], showing functionally alternative splicing on mRNA level. The variant was detected in trans to a pathogenic variant (this case) (PM3), it is very rare (not detected in population databases according to gnomAD [9]) (PM2), prediction algorithms for splicing (Alamut program package) were in favor of a functional effect (PP3). For these reasons, the variant was classified as a variant of uncertain significance according to the ACMG guidelines, with a strong indication towards a pathogenic variant, as it is seen in both affected brothers (and unpublished functional analysis indicate alternative splicing [6]).

Discussion and conclusions

We report two brothers with genetically confirmed spondylodysplastic EDS associated with bi-allelic heterozygous pathogenic variants, a well-known c.641G > A variant and variant c.723 + 4A > G reported only provisionally before [6]. Our findings demonstrate that recurrent pneumothoraces occur in B4GALT7-related spondylodysplastic EDS, thereby expanding the spectrum of clinical presentations.
Clinical features of our patients were besides the major criteria short stature and mild muscular hypotonia, distinct craniofacial features, a developmental delay, and the already described early onset severe hypermetropia [8, 12, 13]. The older brother furthermore had recurrent pneumothoraces, which have not been described in other patients within the spondylodysplastic EDS spectrum and which reoccurred despite pleurodesis. The single other patient compound heterozygous with the c.641G > A variant reported so far, a 3.5 years old male, showed similar clinical symptoms: short stature, hypermobility, hyperelastic skin, as well as motor and cognitive delay [8]. Both of our patients received the diagnosis of hypothyroidism in infancy. Endocrinological manifestations have not been associated with spondylodysplastic EDS so far. Thus, we cannot relate the diagnosis of hypothyroidism with the syndrome in our cases, but also cannot exclude a connection.
Thirty-six patients from 31 families with molecularly confirmed spondylodysplastic EDS due to B4GALT7-deficiency with a total of 13 different variants have been reported so far (Table 2) [8, 1224]. The likely pathogenic c.641G > A variant has been described for the first and only time in 2016 in a single patient [8]. Although the c.723 + 4A > G variant was strictly classified as variant of uncertain significance, the fact that it has been mentioned once in a presentation at the Variant Effect Prediction Training Course (VEPTC) and that it was detected in both brothers with the same clinical phenotype and only heterozygously in a parent strongly indicates a pathogenic effect of the variant. Therefore, our cases present a novel c.723 + 4A > G splice variant that very likely has phenotypical consequences.
Table 2
Patients with B4GALT7 variants: review of the literature
  
Hernandez
et al. (1979, 1981, 1986) [22–24]
Kresse et al. (1987) [14]
Faiyaz-Ul-Haque et al. (2004) [15]
Guo et al. (2013) [16]
Cartault et al. (2015) [18]
Arunrut et al. (2016) [13]
Salter et al. (2016) [8]
Ritelli et al. (2017) [12]
Sandler-Wilson et al. (2019) [19]
Mihalic Mosher et al. (2019) [17]
Caraffi et al. (2019) [20]
This study
Total (patients with mutations)
Genetics
B4GALT7 variants
?
c.557C > A
c.617 T > A
c.808C > T
c.808C > T
c.122 T > C
c.808C > T
c.808C > T
c.808C > T
c.970 T > A
c.970 T > A
c.277dupC
c.641G > A;
c.421C > T
c.808C > T
c.829G > T
c.829G > T
c.421C > T
c.808C > T
c.398A > G
c.808C > T
c.277_278insC
c.628C > T
c.723 + 4A > G
c.641G > A
26/36 homozygous
10/36 compound heterozygous
 
Variants on protein
?
p.A186D
p.L206P
p.R270C
p.R270C
p.L41P
p.R270C
p.R270C
p.R270C
p.C324S
p.C324S
p.H93Pfs*73
p.C214Y;
p.R141W
p.R270C
p.E277*
p.E277*
p.R141W
p.R270C
p.Q133R
p.R270C
p.H93Pfs*73
p.H210Y
splicing
p.C214Y
 
Gender
Male
5
1
1
1
11
 
1
 
1
1
1
2
20
 
Female
  
1
 
11
1
1
1
1
   
16
Age
 
8,15,15, 16,18y
4y 9 m
2, 33y
10y
4 to 46y
5y
3y 6 m, 13y
30y
4,10y
1d†
7y 8 m
15, 18Y
 
Table modified from [20]
The majority of the 13 reported variants associated with spondylodysplastric EDS are localized in the large C-terminal catalytic domain [8, 20], whereas one variant (p.L41P) is localized in the transmembrane domain [16]. The most frequently identified variant is p.R270C. The p.R270 variant was reported in 22 homozygous patients from the same ethnic group (“white creoles”) with Larsen La Reunion syndrome (LRS) [18]. The LRS is more of a skeletal dysplasia phenotype including multiple joint dislocations with ligamentous hyperlaxity and a frequent radioulnar synostosis, as well as severe short stature and distinct facial features [18, 22]. Other studies described varying phenotypes in patients with compound heterozygosity or homozygosity for the p.R270C variant [8, 1517, 19]. Biochemical studies showed a reduced galactosyltransferase activity in patients with p.R270C and p.A186D variants, whereas other variants (p.L206P and p.Q133R) lead to complete loss of enzyme function [4, 5], and correspondingly to severely affected or perinatal lethal phenotypes [14, 17]. The varying phenotypic spectrum within the B4GALT7 related spondylodysplastic EDS, even in patients with the same variant, is not fully understood. Explanations may include fluctuating quantitative effects on glycosaminoglycan biosynthesis, interactions with other variants in close linkage disequilibrium to B4GALT7 and / or the involvement of modifier genes.
The findings in this family expand the clinical phenotype of B4GALT7-spondylodysplastic EDS and provides evidence for the pathogenetic role of the c.723 + 4A > G splice variant. Within the group of patients with a combination of short stature, skeletal and connective tissue abnormalities, next generation sequencing can help to identify the underlying genetic cause.

Declarations

Not applicable.
Written informed consent was obtained from the patients and the patient’s parents for publication of this case report.

Competing interests

The authors declare that they have no competing interests.
Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://​creativecommons.​org/​licenses/​by/​4.​0/​. The Creative Commons Public Domain Dedication waiver (http://​creativecommons.​org/​publicdomain/​zero/​1.​0/​) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Literatur
1.
Zurück zum Zitat Malfait F, Francomano C, Byers P, Belmont J, Berglund B, Black J, et al. The 2017 international classification of the Ehlers-Danlos syndromes. Am J Med Genet C Semin Med Genet. 2017;175(1):8–26.CrossRef Malfait F, Francomano C, Byers P, Belmont J, Berglund B, Black J, et al. The 2017 international classification of the Ehlers-Danlos syndromes. Am J Med Genet C Semin Med Genet. 2017;175(1):8–26.CrossRef
2.
Zurück zum Zitat Colombi M, Dordoni C, Chiarelli N, Ritelli M. Differential diagnosis and diagnostic flow chart of joint hypermobility syndrome/Ehlers-Danlos syndrome hypermobility type compared to other heritable connective tissue disorders. Am J Med Genet C Semin Med Genet. 2015;169C(1):6–22.CrossRef Colombi M, Dordoni C, Chiarelli N, Ritelli M. Differential diagnosis and diagnostic flow chart of joint hypermobility syndrome/Ehlers-Danlos syndrome hypermobility type compared to other heritable connective tissue disorders. Am J Med Genet C Semin Med Genet. 2015;169C(1):6–22.CrossRef
3.
Zurück zum Zitat Brady AF, Demirdas S, Fournel-Gigleux S, Ghali N, Giunta C, Kapferer-Seebacher I, et al. The Ehlers-Danlos syndromes, rare types. Am J Med Genet C Semin Med Genet. 2017;175(1):70–115.CrossRef Brady AF, Demirdas S, Fournel-Gigleux S, Ghali N, Giunta C, Kapferer-Seebacher I, et al. The Ehlers-Danlos syndromes, rare types. Am J Med Genet C Semin Med Genet. 2017;175(1):70–115.CrossRef
4.
Zurück zum Zitat Bui C, Talhaoui I, Chabel M, Mulliert G, Coughtrie MW, Ouzzine M, et al. Molecular characterization of beta1,4-galactosyltransferase 7 genetic mutations linked to the progeroid form of Ehlers-Danlos syndrome (EDS). FEBS Lett. 2010;584(18):3962–8.CrossRef Bui C, Talhaoui I, Chabel M, Mulliert G, Coughtrie MW, Ouzzine M, et al. Molecular characterization of beta1,4-galactosyltransferase 7 genetic mutations linked to the progeroid form of Ehlers-Danlos syndrome (EDS). FEBS Lett. 2010;584(18):3962–8.CrossRef
5.
Zurück zum Zitat Rahuel-Clermont S, Daligault F, Piet MH, Gulberti S, Netter P, Branlant G, et al. Biochemical and thermodynamic characterization of mutated beta1,4-galactosyltransferase 7 involved in the progeroid form of the Ehlers-Danlos syndrome. Biochem J. 2010;432(2):303–11.CrossRef Rahuel-Clermont S, Daligault F, Piet MH, Gulberti S, Netter P, Branlant G, et al. Biochemical and thermodynamic characterization of mutated beta1,4-galactosyltransferase 7 involved in the progeroid form of the Ehlers-Danlos syndrome. Biochem J. 2010;432(2):303–11.CrossRef
7.
Zurück zum Zitat Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, et al. Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med. 2015;17(5):405–24.CrossRef Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, et al. Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med. 2015;17(5):405–24.CrossRef
8.
Zurück zum Zitat Salter CG, Davies JH, Moon RJ, Fairhurst J, Bunyan D, Study DDD, et al. Further defining the phenotypic spectrum of B4GALT7 mutations. Am J Med Genet A. 2016;170(6):1556–63.CrossRef Salter CG, Davies JH, Moon RJ, Fairhurst J, Bunyan D, Study DDD, et al. Further defining the phenotypic spectrum of B4GALT7 mutations. Am J Med Genet A. 2016;170(6):1556–63.CrossRef
9.
Zurück zum Zitat Karczewski KJ, Francioli LC, Tiao G, Cummings BB, Alfoldi J, Wang Q, et al. The mutational constraint spectrum quantified from variation in 141,456 humans. Nature. 2020;581(7809):434–43.CrossRef Karczewski KJ, Francioli LC, Tiao G, Cummings BB, Alfoldi J, Wang Q, et al. The mutational constraint spectrum quantified from variation in 141,456 humans. Nature. 2020;581(7809):434–43.CrossRef
10.
Zurück zum Zitat Adzhubei IA, Schmidt S, Peshkin L, Ramensky VE, Gerasimova A, Bork P, et al. A method and server for predicting damaging missense mutations. Nat Methods. 2010;7(4):248–9.CrossRef Adzhubei IA, Schmidt S, Peshkin L, Ramensky VE, Gerasimova A, Bork P, et al. A method and server for predicting damaging missense mutations. Nat Methods. 2010;7(4):248–9.CrossRef
11.
Zurück zum Zitat Schwarz JM, Cooper DN, Schuelke M, Seelow D. MutationTaster2: mutation prediction for the deep-sequencing age. Nat Methods. 2014;11(4):361–2.CrossRef Schwarz JM, Cooper DN, Schuelke M, Seelow D. MutationTaster2: mutation prediction for the deep-sequencing age. Nat Methods. 2014;11(4):361–2.CrossRef
12.
Zurück zum Zitat Ritelli M, Dordoni C, Cinquina V, Venturini M, Calzavara-Pinton P, Colombi M. Expanding the clinical and mutational spectrum of B4GALT7-spondylodysplastic Ehlers-Danlos syndrome. Orphanet J Rare Dis. 2017;12(1):153.CrossRef Ritelli M, Dordoni C, Cinquina V, Venturini M, Calzavara-Pinton P, Colombi M. Expanding the clinical and mutational spectrum of B4GALT7-spondylodysplastic Ehlers-Danlos syndrome. Orphanet J Rare Dis. 2017;12(1):153.CrossRef
13.
Zurück zum Zitat Arunrut T, Sabbadini M, Jain M, Machol K, Scaglia F, Slavotinek A. Corneal clouding, cataract, and colobomas with a novel missense mutation in B4GALT7-a review of eye anomalies in the linkeropathy syndromes. Am J Med Genet A. 2016;170(10):2711–8.CrossRef Arunrut T, Sabbadini M, Jain M, Machol K, Scaglia F, Slavotinek A. Corneal clouding, cataract, and colobomas with a novel missense mutation in B4GALT7-a review of eye anomalies in the linkeropathy syndromes. Am J Med Genet A. 2016;170(10):2711–8.CrossRef
14.
Zurück zum Zitat Kresse H, Rosthoj S, Quentin E, Hollmann J, Glossl J, Okada S, et al. Glycosaminoglycan-free small proteoglycan core protein is secreted by fibroblasts from a patient with a syndrome resembling progeroid. Am J Hum Genet. 1987;41(3):436–53.PubMedPubMedCentral Kresse H, Rosthoj S, Quentin E, Hollmann J, Glossl J, Okada S, et al. Glycosaminoglycan-free small proteoglycan core protein is secreted by fibroblasts from a patient with a syndrome resembling progeroid. Am J Hum Genet. 1987;41(3):436–53.PubMedPubMedCentral
15.
Zurück zum Zitat Faiyaz-Ul-Haque M, Zaidi SH, Al-Ali M, Al-Mureikhi MS, Kennedy S, Al-Thani G, et al. A novel missense mutation in the galactosyltransferase-I (B4GALT7) gene in a family exhibiting facioskeletal anomalies and Ehlers-Danlos syndrome resembling the progeroid type. Am J Med Genet A. 2004;128A(1):39–45.CrossRef Faiyaz-Ul-Haque M, Zaidi SH, Al-Ali M, Al-Mureikhi MS, Kennedy S, Al-Thani G, et al. A novel missense mutation in the galactosyltransferase-I (B4GALT7) gene in a family exhibiting facioskeletal anomalies and Ehlers-Danlos syndrome resembling the progeroid type. Am J Med Genet A. 2004;128A(1):39–45.CrossRef
16.
Zurück zum Zitat Guo MH, Stoler J, Lui J, Nilsson O, Bianchi DW, Hirschhorn JN, et al. Redefining the progeroid form of Ehlers-Danlos syndrome: report of the fourth patient with B4GALT7 deficiency and review of the literature. Am J Med Genet A. 2013;161A(10):2519–27.PubMed Guo MH, Stoler J, Lui J, Nilsson O, Bianchi DW, Hirschhorn JN, et al. Redefining the progeroid form of Ehlers-Danlos syndrome: report of the fourth patient with B4GALT7 deficiency and review of the literature. Am J Med Genet A. 2013;161A(10):2519–27.PubMed
17.
Zurück zum Zitat Mihalic Mosher T, Zygmunt DA, Koboldt DC, Kelly BJ, Johnson LR, McKenna DS, et al. Expansion of B4GALT7 linkeropathy phenotype to include perinatal lethal skeletal dysplasia. Eur J Hum Genet. 2019;27(10):1569–77.CrossRef Mihalic Mosher T, Zygmunt DA, Koboldt DC, Kelly BJ, Johnson LR, McKenna DS, et al. Expansion of B4GALT7 linkeropathy phenotype to include perinatal lethal skeletal dysplasia. Eur J Hum Genet. 2019;27(10):1569–77.CrossRef
18.
Zurück zum Zitat Cartault F, Munier P, Jacquemont ML, Vellayoudom J, Doray B, Payet C, et al. Expanding the clinical spectrum of B4GALT7 deficiency: homozygous p.R270C mutation with founder effect causes Larsen of Reunion Island syndrome. Eur J Hum Genet. 2015;23(1):49–53.CrossRef Cartault F, Munier P, Jacquemont ML, Vellayoudom J, Doray B, Payet C, et al. Expanding the clinical spectrum of B4GALT7 deficiency: homozygous p.R270C mutation with founder effect causes Larsen of Reunion Island syndrome. Eur J Hum Genet. 2015;23(1):49–53.CrossRef
19.
Zurück zum Zitat Sandler-Wilson C, Wambach JA, Marshall BA, Wegner DJ, McAlister W, Cole FS, et al. Phenotype and response to growth hormone therapy in siblings with B4GALT7 deficiency. Bone. 2019;124:14–21.CrossRef Sandler-Wilson C, Wambach JA, Marshall BA, Wegner DJ, McAlister W, Cole FS, et al. Phenotype and response to growth hormone therapy in siblings with B4GALT7 deficiency. Bone. 2019;124:14–21.CrossRef
20.
Zurück zum Zitat Caraffi SG, Maini I, Ivanovski I, Pollazzon M, Giangiobbe S, Valli M, et al. Severe peripheral joint laxity is a distinctive clinical feature of spondylodysplastic-Ehlers-Danlos syndrome (EDS)-B4GALT7 and spondylodysplastic-EDS-B3GALT6. Genes (Basel). 2019;10(10) Caraffi SG, Maini I, Ivanovski I, Pollazzon M, Giangiobbe S, Valli M, et al. Severe peripheral joint laxity is a distinctive clinical feature of spondylodysplastic-Ehlers-Danlos syndrome (EDS)-B4GALT7 and spondylodysplastic-EDS-B3GALT6. Genes (Basel). 2019;10(10)
21.
Zurück zum Zitat Hernandez A, Aguirre-Negrete MG, Gonzalez-Flores S, Reynoso-Luna MC, Fragoso R, Nazara Z, et al. Ehlers-Danlos features with progeroid facies and mild mental retardation. Further delineation of the syndrome. Clin Genet. 1986;30(6):456–61. Hernandez A, Aguirre-Negrete MG, Gonzalez-Flores S, Reynoso-Luna MC, Fragoso R, Nazara Z, et al. Ehlers-Danlos features with progeroid facies and mild mental retardation. Further delineation of the syndrome. Clin Genet. 1986;30(6):456–61.
22.
Zurück zum Zitat Payet G. Dwarfism and hyperlaxity, facial dysmorphism and multiple dislocations. Larsen’s syndrome? Arch Fr Pediatr. 1975;32(7):601–7.PubMed Payet G. Dwarfism and hyperlaxity, facial dysmorphism and multiple dislocations. Larsen’s syndrome? Arch Fr Pediatr. 1975;32(7):601–7.PubMed
23.
Zurück zum Zitat Hernandez A, Aguirre-Negrete MG, Liparoli JC, Cantu JM. Third case of a distinct variant of the Ehlers-Danlos Syndrome (EDS). Clin Genet. 1981;20(3):222–4. Hernandez A, Aguirre-Negrete MG, Liparoli JC, Cantu JM. Third case of a distinct variant of the Ehlers-Danlos Syndrome (EDS). Clin Genet. 1981;20(3):222–4.
24.
Zurück zum Zitat Hernandez A, Aguirre-Negrete MG, Ramirez-Soltero S, Gonzalez-Mendoza A, Martinez y Martinez R, Velazquez-Cabrera A, et al. A distinct variant of the Ehlers-Danlos syndrome. Clin Genet. 1979;16(5):335–9. Hernandez A, Aguirre-Negrete MG, Ramirez-Soltero S, Gonzalez-Mendoza A, Martinez y Martinez R, Velazquez-Cabrera A, et al. A distinct variant of the Ehlers-Danlos syndrome. Clin Genet. 1979;16(5):335–9.
Metadaten
Titel
Report of two siblings with spondylodysplastic Ehlers-Danlos syndrome and B4GALT7 deficiency
verfasst von
Delia Lorenz
Wolfram Kress
Ann-Kathrin Zaum
Christian P. Speer
Helge Hebestreit
Publikationsdatum
01.12.2021
Verlag
BioMed Central
Erschienen in
BMC Pediatrics / Ausgabe 1/2021
Elektronische ISSN: 1471-2431
DOI
https://doi.org/10.1186/s12887-021-02767-0

Weitere Artikel der Ausgabe 1/2021

BMC Pediatrics 1/2021 Zur Ausgabe

Neuer Typ-1-Diabetes bei Kindern am Wochenende eher übersehen

23.04.2024 Typ-1-Diabetes Nachrichten

Wenn Kinder an Werktagen zum Arzt gehen, werden neu auftretender Typ-1-Diabetes und diabetische Ketoazidosen häufiger erkannt als bei Arztbesuchen an Wochenenden oder Feiertagen.

Neue Studienergebnisse zur Myopiekontrolle mit Atropin

22.04.2024 Fehlsichtigkeit Nachrichten

Augentropfen mit niedrig dosiertem Atropin können helfen, das Fortschreiten einer Kurzsichtigkeit bei Kindern zumindest zu verlangsamen, wie die Ergebnisse einer aktuellen Studie mit verschiedenen Dosierungen zeigen.

Spinale Muskelatrophie: Neugeborenen-Screening lohnt sich

18.04.2024 Spinale Muskelatrophien Nachrichten

Seit 2021 ist die Untersuchung auf spinale Muskelatrophie Teil des Neugeborenen-Screenings in Deutschland. Eine Studie liefert weitere Evidenz für den Nutzen der Maßnahme.

Fünf Dinge, die im Kindernotfall besser zu unterlassen sind

18.04.2024 Pädiatrische Notfallmedizin Nachrichten

Im Choosing-Wisely-Programm, das für die deutsche Initiative „Klug entscheiden“ Pate gestanden hat, sind erstmals Empfehlungen zum Umgang mit Notfällen von Kindern erschienen. Fünf Dinge gilt es demnach zu vermeiden.

Update Pädiatrie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.