Marfan syndrome (MFS) is a relatively common autosomal dominant disorder of connective tissue. It affects many parts of the body involving the skeletal, ocular, and cardiovascular systems. Cardiac manifestations are significant contributors to morbidity and mortality. MFS is caused by mutations in the gene for fibrillin-1.
Category
Congenital malformation
Brite
Human diseases in ICD-11 classification [BR:br08403]
20 Developmental anomalies
Multiple developmental anomalies or syndromes
LD28 Syndromes with connective tissue involvement as a major feature
H00653 Marfan syndrome
Pathway-based classification of diseases [BR:br08402]
Signal transduction
nt06507 TGFB signaling
H00653 Marfan syndrome
Cellular process
nt06539 Cytoskeleton in muscle cells
H00653 Marfan syndrome
nt06548 Integrin signaling
H00653 Marfan syndrome
MASS Phenotype (Mitral valve prolapse, Aortic dilatation without dissection, Skeletal and Skin abnormalities) is one of the FBN1-related disorders similar to Marfan syndrome. Reduced expression of FBN1 due to a 4 bp deletion in exon 41 is the cause of MASS phenotype.
Category
Congenital malformation
Brite
Human diseases in ICD-11 classification [BR:br08403]
20 Developmental anomalies
Multiple developmental anomalies or syndromes
LD28 Syndromes with connective tissue involvement as a major feature
H00661 MASS phenotype
Pathway-based classification of diseases [BR:br08402]
Cellular process
nt06548 Integrin signaling
H00661 MASS phenotype
Ectopia lentis (EL) is defined as displacement or malposition of the crystalline lens of the eye and is inherited in either autosomal recessive or autosomal dominant manner. Subluxation of the lens is slowly progressive in the first two decades of life. EL may occur as an isolated form or as a part of disorders. Up to about 80% of Marfan syndrome (MFS) patients have bilateral EL. Several genes have been identified that may be involved in the development of nonsyndromic ectopia lentis. Variable expressivity of fibrillin (FBN1) mutations has been associated with autosomal dominant forms. Recently, mutations in ADAMTSL4 have been reported in families with isolated autosomal recessive ectopia lentis. It has been shown that ectopia lentis et pupillae is also caused by the mutation in ADAMTSL4.
Category
Congenital malformation
Brite
Human diseases in ICD-11 classification [BR:br08403]
20 Developmental anomalies
Structural developmental anomalies primarily affecting one body system
Structural developmental anomalies of the eye, eyelid or lacrimal apparatus
LA12 Structural developmental anomalies of lens or zonula
H00662 Ectopia lentis
Pathway-based classification of diseases [BR:br08402]
Cellular process
nt06548 Integrin signaling
H00662 Ectopia lentis
Weill-Marchesani syndrome (WMS) is a rare connective tissue disorder characterized by short stature, brachydactyly, ectopia lentis and spherophakia. Decreased joint flexibility is one of the features of this syndrome.
Category
Congenital malformation
Brite
Human diseases in ICD-11 classification [BR:br08403]
20 Developmental anomalies
Multiple developmental anomalies or syndromes
LD21 Syndromes with eye anomalies as a major feature
H00673 Weill-Marchesani syndrome
Pathway-based classification of diseases [BR:br08402]
Cellular process
nt06539 Cytoskeleton in muscle cells
H00673 Weill-Marchesani syndrome
nt06548 Integrin signaling
H00673 Weill-Marchesani syndrome
Geleophysic dysplasia (GPHYSD) is an autosomal recessive disorder resembling a lysosomal storage disorder. It is characterized by short stature, short hands and feet due to short, plump tubular bones, stiff joints, distinctive facial features, and progressive valvular cardiac disease.
Category
Congenital malformation
Brite
Human diseases in ICD-11 classification [BR:br08403]
20 Developmental anomalies
Multiple developmental anomalies or syndromes
LD24 Syndromes with skeletal anomalies as a major feature
H00900 Geleophysic dysplasia
Pathway-based classification of diseases [BR:br08402]
Signal transduction
nt06507 TGFB signaling
H00900 Geleophysic dysplasia
Cellular process
nt06539 Cytoskeleton in muscle cells
H00900 Geleophysic dysplasia
nt06548 Integrin signaling
H00900 Geleophysic dysplasia
Allali S, Le Goff C, Pressac-Diebold I, Pfennig G, Mahaut C, Dagoneau N, Alanay Y, Brady AF, Crow YJ, Devriendt K, Drouin-Garraud V, Flori E, Genevieve D, Hennekam RC, Hurst J, Krakow D, Le Merrer M, Lichtenbelt KD, Lynch SA, Lyonnet S, MacDermot K, Mansour S, Megarbane A, Santos HG, Splitt M, Superti-Furga A, Unger S, Williams D, Munnich A, Cormier-Daire V
Title
Molecular screening of ADAMTSL2 gene in 33 patients reveals the genetic heterogeneity of geleophysic dysplasia.
McInerney-Leo AM, Le Goff C, Leo PJ, Kenna TJ, Keith P, Harris JE, Steer R, Bole-Feysot C, Nitschke P, Kielty C, Brown MA, Zankl A, Duncan EL, Cormier-Daire V
Title
Mutations in LTBP3 cause acromicric dysplasia and geleophysic dysplasia.
Stiff skin syndrome (SSS) is an autosomal dominant congenital form of scleroderma characterized by stony-hard skin, limitation of joint mobility, and mild hypertrichosis, remarkable in the areas with abundant fascia on the thighs and buttocks. SSS is caused by mutations in the Arg-Gly-Asp (RGD) sequence-encoding domain of fibrillin-1 that mediates integrin binding.
Category
Skin disease
Brite
Human diseases in ICD-11 classification [BR:br08403]
14 Diseases of the skin
Skin disorders involving specific cutaneous structures
Disorders of the dermis and subcutis
Disorders of cutaneous connective tissue
Fibromatoses and keloids
EE6Y Other specified fibromatous disorders of skin and soft tissue
H01173 Stiff skin syndrome
Pathway-based classification of diseases [BR:br08402]
Cellular process
nt06539 Cytoskeleton in muscle cells
H01173 Stiff skin syndrome
nt06548 Integrin signaling
H01173 Stiff skin syndrome
Acromicric dysplasia (ACMICD) is a rare autosomal dominant bone dysplasia characterised by severe short stature, short hands and feet, joint limitations, skin thickening, and distinct facial features. It has been reported that mutations in FBN1 are responsible for this disease.
Category
Congenital malformation
Brite
Human diseases in ICD-11 classification [BR:br08403]
20 Developmental anomalies
Multiple developmental anomalies or syndromes
LD24 Syndromes with skeletal anomalies as a major feature
H02228 Acromicric dysplasia
Pathway-based classification of diseases [BR:br08402]
Cellular process
nt06539 Cytoskeleton in muscle cells
H02228 Acromicric dysplasia
nt06548 Integrin signaling
H02228 Acromicric dysplasia
Faivre L, Le Merrer M, Baumann C, Polak M, Chatelain P, Sulmont V, Cousin J, Bost M, Cordier MP, Zackai E, Russell K, Finidori G, Pouliquen JC, Munnich A, Maroteaux P, Cormier-Daire V
Title
Acromicric dysplasia: long term outcome and evidence of autosomal dominant inheritance.
