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Progeroid and marfanoid aspect-lipodystrophy syndrome(MFLS)

MedGen UID:
934763
Concept ID:
C4310796
Disease or Syndrome
Synonyms: Marfan lipodystrophy syndrome; MARFAN-PROGEROID-LIPODYSTROPHY SYNDROME; MARFANOID-PROGEROID SYNDROME; MARFANOID-PROGEROID-LIPODYSTROPHY SYNDROME
Modes of inheritance:
Autosomal dominant inheritance
MedGen UID:
141047
Concept ID:
C0443147
Intellectual Product
Source: Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in heterozygotes. In the context of medical genetics, an autosomal dominant disorder is caused when a single copy of the mutant allele is present. Males and females are affected equally, and can both transmit the disorder with a risk of 50% for each child of inheriting the mutant allele.
 
Gene (location): FBN1 (15q21.1)
 
Monarch Initiative: MONDO:0014831
OMIM®: 616914
Orphanet: ORPHA300382

Definition

The marfanoid-progeroid-lipodystrophy syndrome (MFLS) is characterized by congenital lipodystrophy, premature birth with an accelerated linear growth disproportionate to weight gain, and progeroid appearance with distinct facial features, including proptosis, downslanting palpebral fissures, and retrognathia. Other characteristic features include arachnodactyly, digital hyperextensibility, myopia, dural ectasia, and normal psychomotor development (Takenouchi et al., 2013). Takenouchi et al. (2013) noted phenotypic overlap with Marfan syndrome (154700) and Shprintzen-Goldberg craniosynostosis syndrome (182212). [from OMIM]

Clinical features

From HPO
Arachnodactyly
MedGen UID:
2047
Concept ID:
C0003706
Congenital Abnormality
Abnormally long and slender fingers (spider fingers).
Pes planus
MedGen UID:
42034
Concept ID:
C0016202
Anatomical Abnormality
A foot where the longitudinal arch of the foot is in contact with the ground or floor when the individual is standing; or, in a patient lying supine, a foot where the arch is in contact with the surface of a flat board pressed against the sole of the foot by the examiner with a pressure similar to that expected from weight bearing; or, the height of the arch is reduced.
Scapular winging
MedGen UID:
66822
Concept ID:
C0240953
Anatomical Abnormality
Abnormal protrusion of the scapula away from the surface of the back.
Pes valgus
MedGen UID:
299028
Concept ID:
C1578482
Anatomical Abnormality
An outward deviation of the foot at the talocalcaneal or subtalar joint.
Long fingers
MedGen UID:
346836
Concept ID:
C1858091
Finding
The middle finger is more than 2 SD above the mean for newborns 27 to 41 weeks EGA or above the 97th centile for children from birth to 16 years of age AND the five digits retain their normal length proportions relative to each other (i.e., it is not the case that the middle finger is the only lengthened digit), or, Fingers that appear disproportionately long compared to the palm of the hand.
Hypertensive disorder
MedGen UID:
6969
Concept ID:
C0020538
Disease or Syndrome
The presence of chronic increased pressure in the systemic arterial system.
Mitral valve prolapse
MedGen UID:
7671
Concept ID:
C0026267
Disease or Syndrome
One or both of the leaflets (cusps) of the mitral valve bulges back into the left atrium upon contraction of the left ventricle.
Aortic root aneurysm
MedGen UID:
720712
Concept ID:
C1298820
Anatomical Abnormality
An abnormal localized widening (dilatation) of the aortic root.
Fetal growth restriction
MedGen UID:
4693
Concept ID:
C0015934
Pathologic Function
An abnormal restriction of fetal growth with fetal weight below the tenth percentile for gestational age.
Tall stature
MedGen UID:
69137
Concept ID:
C0241240
Finding
A height above that which is expected according to age and gender norms.
Feeding difficulties in infancy
MedGen UID:
436211
Concept ID:
C2674608
Finding
Impaired feeding performance of an infant as manifested by difficulties such as weak and ineffective sucking, brief bursts of sucking, and falling asleep during sucking. There may be difficulties with chewing or maintaining attention.
Hydrocephalus
MedGen UID:
9335
Concept ID:
C0020255
Disease or Syndrome
Hydrocephalus is an active distension of the ventricular system of the brain resulting from inadequate passage of CSF from its point of production within the cerebral ventricles to its point of absorption into the systemic circulation.
Dural ectasia
MedGen UID:
377094
Concept ID:
C1851712
Finding
A widening or ballooning of the dural sac surrounding the spinal cord usually at the lumbosacral level.
Motor delay
MedGen UID:
381392
Concept ID:
C1854301
Finding
A type of Developmental delay characterized by a delay in acquiring motor skills.
Lateral ventricular asymmetry
MedGen UID:
867526
Concept ID:
C4021909
Anatomical Abnormality
Abnormal difference in size between the left and right lateral cerebral ventricles.
Neurodevelopmental abnormality
MedGen UID:
868343
Concept ID:
C4022737
Pathologic Function
A deviation from normal of the neurological development of a child, which may include any or all of the aspects of the development of personal, social, gross or fine motor, and cognitive abilities.
Craniosynostosis syndrome
MedGen UID:
1163
Concept ID:
C0010278
Disease or Syndrome
Craniosynostosis refers to the premature closure of the cranial sutures. Primary craniosynostosis refers to the closure of one or more sutures due to abnormalities in skull development, and secondary craniosynostosis results from failure of brain growth.
Kyphosis
MedGen UID:
44042
Concept ID:
C0022821
Anatomical Abnormality
Exaggerated anterior convexity of the thoracic vertebral column.
Hypotonia
MedGen UID:
10133
Concept ID:
C0026827
Finding
Hypotonia is an abnormally low muscle tone (the amount of tension or resistance to movement in a muscle). Even when relaxed, muscles have a continuous and passive partial contraction which provides some resistance to passive stretching. Hypotonia thus manifests as diminished resistance to passive stretching. Hypotonia is not the same as muscle weakness, although the two conditions can co-exist.
Retrognathia
MedGen UID:
19766
Concept ID:
C0035353
Congenital Abnormality
An abnormality in which the mandible is mislocalised posteriorly.
Absence of subcutaneous fat
MedGen UID:
69138
Concept ID:
C0241267
Finding
Lack of subcutaneous adipose tissue.
Isolated scaphocephaly
MedGen UID:
82712
Concept ID:
C0265534
Congenital Abnormality
Scaphocephaly is a subtype of dolichocephaly where the anterior and posterior aspects of the cranial vault are pointed (boat-shaped). Scaphocephaly is caused by a precocious fusion of sagittal suture without other associated synostosis.
Narrow chest
MedGen UID:
96528
Concept ID:
C0426790
Finding
Reduced width of the chest from side to side, associated with a reduced distance from the sternal notch to the tip of the shoulder.
Lipoatrophy
MedGen UID:
488959
Concept ID:
C1280433
Disease or Syndrome
Localized loss of fat tissue.
Hyperextensibility of the finger joints
MedGen UID:
334982
Concept ID:
C1844577
Finding
The ability of the finger joints to move beyond their normal range of motion.
Reduced subcutaneous adipose tissue
MedGen UID:
387876
Concept ID:
C1857657
Finding
A reduced amount of fat tissue in the lowest layer of the integument. This feature can be appreciated by a reduced skinfold thickness.
Pectus excavatum
MedGen UID:
781174
Concept ID:
C2051831
Finding
A defect of the chest wall characterized by a depression of the sternum, giving the chest ("pectus") a caved-in ("excavatum") appearance.
Macrocephaly
MedGen UID:
745757
Concept ID:
C2243051
Finding
Occipitofrontal (head) circumference greater than 97th centile compared to appropriate, age matched, sex-matched normal standards. Alternatively, a apparently increased size of the cranium.
Generalized lipodystrophy
MedGen UID:
1369615
Concept ID:
C4317112
Disease or Syndrome
Generalized degenerative changes of the fat tissue.
Keratoconjunctivitis sicca
MedGen UID:
9620
Concept ID:
C0022575
Disease or Syndrome
Dryness of the eye related to deficiency of the tear film components (aqueous, mucin, or lipid), lid surface abnormalities, or epithelial abnormalities. Keratoconjunctivitis sicca often results in a scratchy or sandy sensation (foreign body sensation) in the eyes, and may also be associated with itching, inability to produce tears, photosensitivity, redness, pain, and difficulty in moving the eyelids.
High palate
MedGen UID:
66814
Concept ID:
C0240635
Congenital Abnormality
Height of the palate more than 2 SD above the mean (objective) or palatal height at the level of the first permanent molar more than twice the height of the teeth (subjective).
Downslanted palpebral fissures
MedGen UID:
98391
Concept ID:
C0423110
Finding
The palpebral fissure inclination is more than two standard deviations below the mean.
Narrow nose
MedGen UID:
98086
Concept ID:
C0426422
Finding
Interalar distance more than 2 SD below the mean for age, or alternatively, an apparently decreased width of the nasal base and alae.
Triangular face
MedGen UID:
324383
Concept ID:
C1835884
Finding
Facial contour, as viewed from the front, triangular in shape, with breadth at the temples and tapering to a narrow chin.
Prominent forehead
MedGen UID:
373291
Concept ID:
C1837260
Finding
Forward prominence of the entire forehead, due to protrusion of the frontal bone.
High, narrow palate
MedGen UID:
324787
Concept ID:
C1837404
Finding
The presence of a high and narrow palate.
Narrow nasal ridge
MedGen UID:
373404
Concept ID:
C1837761
Finding
Decreased width of the nasal ridge.
Broad forehead
MedGen UID:
338610
Concept ID:
C1849089
Finding
Width of the forehead or distance between the frontotemporales is more than two standard deviations above the mean (objective); or apparently increased distance between the two sides of the forehead.
Prominent nasal bridge
MedGen UID:
343051
Concept ID:
C1854113
Finding
Anterior positioning of the nasal root in comparison to the usual positioning for age.
Melanocytic nevus
MedGen UID:
14364
Concept ID:
C0027962
Neoplastic Process
A oval and round, colored (usually medium-to dark brown, reddish brown, or flesh colored) lesion. Typically, a melanocytic nevus is less than 6 mm in diameter, but may be much smaller or larger.
Bruising susceptibility
MedGen UID:
140849
Concept ID:
C0423798
Finding
An ecchymosis (bruise) refers to the skin discoloration caused by the escape of blood into the tissues from ruptured blood vessels. This term refers to an abnormally increased susceptibility to bruising. The corresponding phenotypic abnormality is generally elicited on medical history as a report of frequent ecchymoses or bruising without adequate trauma.
Progeroid facial appearance
MedGen UID:
341830
Concept ID:
C1857710
Finding
A degree of wrinkling of the facial skin that is more than expected for the age of the individual, leading to a prematurely aged appearance.
Oligohydramnios
MedGen UID:
86974
Concept ID:
C0079924
Pathologic Function
Diminished amniotic fluid volume in pregnancy.
Premature birth
MedGen UID:
57721
Concept ID:
C0151526
Pathologic Function
The birth of a baby of less than 37 weeks of gestational age.
Ectopia lentis
MedGen UID:
41704
Concept ID:
C0013581
Congenital Abnormality
Dislocation or malposition of the crystalline lens of the eye. A partial displacement (or dislocation) of the lens is described as a subluxation of the lens, while a complete displacement is termed luxation of the lens. A complete displacement occurs if the lens is completely outside the patellar fossa of the lens, either in the anterior chamber, in the vitreous, or directly on the retina. If the lens is partially displaced but still contained within the lens space, then it is termed subluxation.
Proptosis
MedGen UID:
41917
Concept ID:
C0015300
Disease or Syndrome
An eye that is protruding anterior to the plane of the face to a greater extent than is typical.
Reduced visual acuity
MedGen UID:
65889
Concept ID:
C0234632
Finding
Diminished clarity of vision.
High myopia
MedGen UID:
78759
Concept ID:
C0271183
Disease or Syndrome
A severe form of myopia with greater than -6.00 diopters.
Deeply set eye
MedGen UID:
473112
Concept ID:
C0423224
Finding
An eye that is more deeply recessed into the plane of the face than is typical.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVProgeroid and marfanoid aspect-lipodystrophy syndrome

Recent clinical studies

Diagnosis

Lin M, Liu Z, Liu G, Zhao S, Li C, Chen W, Coban Akdemir Z, Lin J, Song X, Wang S, Xu Q, Zhao Y, Wang L, Zhang Y, Yan Z, Liu S, Liu J, Chen Y, Zuo Y, Yang X, Sun T, Yang XZ, Niu Y, Li X, You W, Qiu B, Ding C, Liu P, Zhang S, Carvalho CMB, Posey JE, Qiu G; Deciphering Disorders Involving Scoliosis and COmorbidities (DISCO) study, Lupski JR, Wu Z, Zhang J, Wu N
Mol Genet Genomic Med 2020 Jan;8(1):e1023. Epub 2019 Nov 27 doi: 10.1002/mgg3.1023. PMID: 31774634Free PMC Article
Passarge E, Robinson PN, Graul-Neumann LM
Eur J Hum Genet 2016 Aug;24(9):1244-7. Epub 2016 Feb 10 doi: 10.1038/ejhg.2016.6. PMID: 26860060Free PMC Article
Jacquinet A, Verloes A, Callewaert B, Coremans C, Coucke P, de Paepe A, Kornak U, Lebrun F, Lombet J, Piérard GE, Robinson PN, Symoens S, Van Maldergem L, Debray FG
Eur J Med Genet 2014 Apr;57(5):230-4. Epub 2014 Mar 6 doi: 10.1016/j.ejmg.2014.02.012. PMID: 24613577
Goldblatt J, Hyatt J, Edwards C, Walpole I
Am J Med Genet A 2011 Apr;155A(4):717-20. Epub 2011 Mar 15 doi: 10.1002/ajmg.a.33906. PMID: 21594992

Prognosis

Lin M, Liu Z, Liu G, Zhao S, Li C, Chen W, Coban Akdemir Z, Lin J, Song X, Wang S, Xu Q, Zhao Y, Wang L, Zhang Y, Yan Z, Liu S, Liu J, Chen Y, Zuo Y, Yang X, Sun T, Yang XZ, Niu Y, Li X, You W, Qiu B, Ding C, Liu P, Zhang S, Carvalho CMB, Posey JE, Qiu G; Deciphering Disorders Involving Scoliosis and COmorbidities (DISCO) study, Lupski JR, Wu Z, Zhang J, Wu N
Mol Genet Genomic Med 2020 Jan;8(1):e1023. Epub 2019 Nov 27 doi: 10.1002/mgg3.1023. PMID: 31774634Free PMC Article

Clinical prediction guides

Lin M, Liu Z, Liu G, Zhao S, Li C, Chen W, Coban Akdemir Z, Lin J, Song X, Wang S, Xu Q, Zhao Y, Wang L, Zhang Y, Yan Z, Liu S, Liu J, Chen Y, Zuo Y, Yang X, Sun T, Yang XZ, Niu Y, Li X, You W, Qiu B, Ding C, Liu P, Zhang S, Carvalho CMB, Posey JE, Qiu G; Deciphering Disorders Involving Scoliosis and COmorbidities (DISCO) study, Lupski JR, Wu Z, Zhang J, Wu N
Mol Genet Genomic Med 2020 Jan;8(1):e1023. Epub 2019 Nov 27 doi: 10.1002/mgg3.1023. PMID: 31774634Free PMC Article

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