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Wrinkly skin syndrome(WSS)

MedGen UID:
98030
Concept ID:
C0406587
Disease or Syndrome
Synonyms: Type of Gerodermia osteodysplastica; WSS
SNOMED CT: WSS - Wrinkly skin syndrome (238875009); Wrinkly skin syndrome (238875009)
Modes of inheritance:
Autosomal recessive inheritance
MedGen UID:
141025
Concept ID:
C0441748
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 individuals with two pathogenic alleles, either homozygotes (two copies of the same mutant allele) or compound heterozygotes (whereby each copy of a gene has a distinct mutant allele).
 
Gene (location): ATP6V0A2 (12q24.31)
 
Monarch Initiative: MONDO:0010208
OMIM®: 278250
Orphanet: ORPHA2834

Disease characteristics

Excerpted from the GeneReview: ATP6V0A2-Related Cutis Laxa
ATP6V0A2-related cutis laxa is characterized by generalized cutis laxa, findings associated with generalized connective tissue disorder, developmental delays, and a variety of neurologic findings including abnormality on brain MRI. At birth, hypotonia, overfolded skin, and distinctive facial features are present and enlarged fontanelles are often observed. During childhood, the characteristic facial features and thick or coarse hair may become quite pronounced. The skin findings decrease with age, although easy bruising and Ehlers-Danlos-like scars have been described in some. In most (not all) affected individuals, cortical and cerebellar malformations are observed on brain MRI. Nearly all affected individuals have developmental delays, seizures, and neurologic regression. [from GeneReviews]
Authors:
Lionel Van Maldergem  |  William Dobyns  |  Uwe Kornak   view full author information

Additional description

From OMIM
Wrinkly skin syndrome (WSS) evolves during early childhood and includes generalized and excessive skin wrinkling, dental problems, herniae, foot deformities, hip dislocations, growth retardation, and a large anterior fontanel. The facial gestalt is characterized by a broad nasal bridge, hypertelorism, and downslanting palpebral fissures (summary by Rajab et al., 2008).  http://www.omim.org/entry/278250

Clinical features

From HPO
Cryptorchidism
MedGen UID:
8192
Concept ID:
C0010417
Congenital Abnormality
Cryptorchidism, or failure of testicular descent, is a common human congenital abnormality with a multifactorial etiology that likely reflects the involvement of endocrine, environmental, and hereditary factors. Cryptorchidism can result in infertility and increases risk for testicular tumors. Testicular descent from abdomen to scrotum occurs in 2 distinct phases: the transabdominal phase and the inguinoscrotal phase (summary by Gorlov et al., 2002).
Clubfoot
MedGen UID:
3130
Concept ID:
C0009081
Congenital Abnormality
Clubfoot is a congenital limb deformity defined as fixation of the foot in cavus, adductus, varus, and equinus (i.e., inclined inwards, axially rotated outwards, and pointing downwards) with concomitant soft tissue abnormalities (Cardy et al., 2007). Clubfoot may occur in isolation or as part of a syndrome (e.g., diastrophic dysplasia, 222600). Clubfoot has been reported with deficiency of long bones and mirror-image polydactyly (Gurnett et al., 2008; Klopocki et al., 2012).
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.
Deep palmar crease
MedGen UID:
387849
Concept ID:
C1857539
Finding
Excessively deep creases of the palm.
Coxa vara
MedGen UID:
1790477
Concept ID:
C5551440
Anatomical Abnormality
Coxa vara includes all forms of decrease of the femoral neck shaft angle (the angle between the neck and the shaft of the femur) to less than 120 degrees.
Muscular ventricular septal defect
MedGen UID:
473253
Concept ID:
C0685707
Congenital Abnormality
The trabecular septum is the largest part of the interventricular septum. It extends from the membranous septum to the apex and superiorly to the infundibular septum. A defect in the trabecular septum is called muscular VSD if the defect is completely rimmed by muscle.
Atrial septal dilatation
MedGen UID:
1384602
Concept ID:
C4476553
Anatomical Abnormality
A bulging of the interatrial septum towards one side. In adults, atrial septal aneurysm can be defined as a protrusion of the aneurysm of >10 mm beyond the plane of the atrial septum as measured by transesophageal echocardiography.
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.
Short stature
MedGen UID:
87607
Concept ID:
C0349588
Finding
A height below that which is expected according to age and gender norms. Although there is no universally accepted definition of short stature, many refer to "short stature" as height more than 2 standard deviations below the mean for age and gender (or below the 3rd percentile for age and gender dependent norms).
Failure to thrive
MedGen UID:
746019
Concept ID:
C2315100
Disease or Syndrome
Failure to thrive (FTT) refers to a child whose physical growth is substantially below the norm.
Low-set ears
MedGen UID:
65980
Concept ID:
C0239234
Congenital Abnormality
Upper insertion of the ear to the scalp below an imaginary horizontal line drawn between the inner canthi of the eye and extending posteriorly to the ear.
Delayed speech and language development
MedGen UID:
105318
Concept ID:
C0454644
Finding
A degree of language development that is significantly below the norm for a child of a specified age.
Intellectual disability
MedGen UID:
811461
Concept ID:
C3714756
Mental or Behavioral Dysfunction
Intellectual disability, previously referred to as mental retardation, is characterized by subnormal intellectual functioning that occurs during the developmental period. It is defined by an IQ score below 70.
Inguinal hernia
MedGen UID:
6817
Concept ID:
C0019294
Finding
Protrusion of the contents of the abdominal cavity through the inguinal canal.
Umbilical hernia
MedGen UID:
9232
Concept ID:
C0019322
Anatomical Abnormality
Protrusion of abdominal contents through a defect in the abdominal wall musculature around the umbilicus. Skin and subcutaneous tissue overlie the defect.
Congenital hip dislocation
MedGen UID:
9258
Concept ID:
C0019555
Disease or Syndrome
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.
Osteopenia
MedGen UID:
18222
Concept ID:
C0029453
Disease or Syndrome
Osteopenia is a term to define bone density that is not normal but also not as low as osteoporosis. By definition from the World Health Organization osteopenia is defined by bone densitometry as a T score -1 to -2.5.
Scoliosis
MedGen UID:
11348
Concept ID:
C0036439
Disease or Syndrome
The presence of an abnormal lateral curvature of the spine.
Hypoplasia of the musculature
MedGen UID:
66010
Concept ID:
C0240414
Finding
Underdevelopment of the musculature.
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.
Delayed cranial suture closure
MedGen UID:
75805
Concept ID:
C0277828
Finding
Infants normally have two fontanels at birth, the diamond-shaped anterior fontanelle at the junction of the coronal and sagittal sutures, and the posterior fontanelle at the intersection of the occipital and parietal bones. The posterior fontanelle usually closes by the 8th week of life, and the anterior fontanel closes by the 18th month of life on average. This term applies if there is delay of closure of the fontanelles beyond the normal age.
Slender long bone
MedGen UID:
331446
Concept ID:
C1833144
Finding
Reduced diameter of a long bone.
Microretrognathia
MedGen UID:
326907
Concept ID:
C1839546
Finding
A form of developmental hypoplasia of the mandible in which the mandible is mislocalised posteriorly.
Joint hypermobility
MedGen UID:
336793
Concept ID:
C1844820
Finding
The capability that a joint (or a group of joints) has to move, passively and/or actively, beyond normal limits along physiological axes.
Progressive microcephaly
MedGen UID:
340542
Concept ID:
C1850456
Anatomical Abnormality
Progressive microcephaly is diagnosed when the head circumference falls progressively behind age- and gender-dependent norms.
Wide anterior fontanel
MedGen UID:
400926
Concept ID:
C1866134
Finding
Enlargement of the anterior fontanelle with respect to age-dependent norms.
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.
Wormian bones
MedGen UID:
766814
Concept ID:
C3553900
Congenital Abnormality
The presence of extra bones within a cranial suture. Wormian bones are irregular isolated bones which appear in addition to the usual centers of ossification of the cranium.
Delayed closure of the anterior fontanelle
MedGen UID:
825928
Concept ID:
C3840083
Finding
A delay in closure (ossification) of the anterior fontanelle, which generally undergoes closure around the 18th month of life.
Microcephaly
MedGen UID:
1644158
Concept ID:
C4551563
Finding
Head circumference below 2 standard deviations below the mean for age and gender.
Abnormal isoelectric focusing of serum transferrin
MedGen UID:
413671
Concept ID:
C2749688
Finding
Glycosylated transferrin concentrations can be measured in serum as a marker of N-linked glycosylation fidelity. In the traditional nomenclature for congenital disorders of glycosylation, absence of entire glycans was designated type I, and loss of one or more monosaccharides as type II. These terms are retained for historical reasons but for new annotations the precise glycosylation defect should be recorded.
Hypernasal speech
MedGen UID:
99115
Concept ID:
C0454555
Finding
A type of speech characterized by the presence of an abnormally increased nasal airflow during speech associated with structural abnormality of the nasal passages.
Carious teeth
MedGen UID:
8288
Concept ID:
C0011334
Disease or Syndrome
Caries is a multifactorial bacterial infection affecting the structure of the tooth. This term has been used to describe the presence of more than expected dental caries.
Delayed eruption of teeth
MedGen UID:
68678
Concept ID:
C0239174
Finding
Delayed tooth eruption, which can be defined as tooth eruption more than 2 SD beyond the mean eruption age.
Microdontia
MedGen UID:
66008
Concept ID:
C0240340
Congenital Abnormality
Decreased size of the teeth, which can be defined as a mesiodistal tooth diameter (width) more than 2 SD below mean. Alternatively, an apparently decreased maximum width of tooth.
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.
Epicanthus
MedGen UID:
151862
Concept ID:
C0678230
Congenital Abnormality
Epicanthus is a condition in which a fold of skin stretches from the upper to the lower eyelid, partially covering the inner canthus. Usher (1935) noted that epicanthus is a normal finding in the fetus of all races. Epicanthus also occurs in association with hereditary ptosis (110100).
Smooth philtrum
MedGen UID:
222980
Concept ID:
C1142533
Finding
Flat skin surface, with no ridge formation in the central region of the upper lip between the nasal base and upper vermilion border.
Wide nasal bridge
MedGen UID:
341441
Concept ID:
C1849367
Finding
Increased breadth of the nasal bridge (and with it, the nasal root).
Long philtrum
MedGen UID:
351278
Concept ID:
C1865014
Finding
Distance between nasal base and midline upper lip vermilion border more than 2 SD above the mean. Alternatively, an apparently increased distance between nasal base and midline upper lip vermilion border.
Short nail
MedGen UID:
140850
Concept ID:
C0423808
Finding
Decreased length of nail.
Redundant skin
MedGen UID:
154379
Concept ID:
C0581342
Pathologic Function
Loose and sagging skin often associated with loss of skin elasticity.
Palmoplantar cutis laxa
MedGen UID:
341602
Concept ID:
C1856714
Finding
Loose, wrinkled skin of hands and feet.
Fragile nails
MedGen UID:
341661
Concept ID:
C1856963
Finding
Nails that easily break.
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.
Deep plantar creases
MedGen UID:
341890
Concept ID:
C1857953
Finding
The presence of unusually deep creases (ridges/wrinkles) on the skin of sole of foot.
Neonatal wrinkled skin of hands and feet
MedGen UID:
870438
Concept ID:
C4024884
Finding
Sparse hair
MedGen UID:
1790211
Concept ID:
C5551005
Finding
Reduced density of hairs.
Premature rupture of membranes
MedGen UID:
8826
Concept ID:
C0015944
Pathologic Function
Premature rupture of membranes (PROM) is a condition which occurs in pregnancy when the amniotic sac ruptures more than an hour before the onset of labor.
Hypertelorism
MedGen UID:
9373
Concept ID:
C0020534
Finding
Although hypertelorism means an excessive distance between any paired organs (e.g., the nipples), the use of the word has come to be confined to ocular hypertelorism. Hypertelorism occurs as an isolated feature and is also a feature of many syndromes, e.g., Opitz G syndrome (see 300000), Greig cephalopolysyndactyly (175700), and Noonan syndrome (163950) (summary by Cohen et al., 1995).
Blue sclerae
MedGen UID:
154236
Concept ID:
C0542514
Finding
An abnormal bluish coloration of the sclera.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVWrinkly skin syndrome
Follow this link to review classifications for Wrinkly skin syndrome in Orphanet.

Professional guidelines

PubMed

Dimopoulou A, Fischer B, Gardeitchik T, Schröter P, Kayserili H, Schlack C, Li Y, Brum JM, Barisic I, Castori M, Spaich C, Fletcher E, Mahayri Z, Bhat M, Girisha KM, Lachlan K, Johnson D, Phadke S, Gupta N, Simandlova M, Kabra M, David A, Nijtmans L, Chitayat D, Tuysuz B, Brancati F, Mundlos S, Van Maldergem L, Morava E, Wollnik B, Kornak U
Mol Genet Metab 2013 Nov;110(3):352-61. Epub 2013 Aug 24 doi: 10.1016/j.ymgme.2013.08.009. PMID: 24035636

Recent clinical studies

Etiology

Myung DB, Lee JH, Han HS, Lee KY, Ahn HS, Shin YK, Song E, Kim BH, Lee KH, Lee SH, Lee KT
Nutrients 2020 May 28;12(6) doi: 10.3390/nu12061588. PMID: 32481760Free PMC Article
Skidmore DL, Chitayat D, Morgan T, Hinek A, Fischer B, Dimopoulou A, Somers G, Halliday W, Blaser S, Diambomba Y, Lemire EG, Kornak U, Robertson SP
Am J Med Genet A 2011 Aug;155A(8):1848-56. Epub 2011 Jul 7 doi: 10.1002/ajmg.a.34057. PMID: 21739576
Kornak U, Reynders E, Dimopoulou A, van Reeuwijk J, Fischer B, Rajab A, Budde B, Nürnberg P, Foulquier F; ARCL Debré-type Study Group, Lefeber D, Urban Z, Gruenewald S, Annaert W, Brunner HG, van Bokhoven H, Wevers R, Morava E, Matthijs G, Van Maldergem L, Mundlos S
Nat Genet 2008 Jan;40(1):32-4. Epub 2007 Dec 23 doi: 10.1038/ng.2007.45. PMID: 18157129
Gupta N, Phadke SR
Pediatr Dermatol 2006 May-Jun;23(3):225-30. doi: 10.1111/j.1525-1470.2006.00222.x. PMID: 16780467
Salih MA, Murshid WR, Al-Salman MM, Abdel-Gader AG, Al-Jarallah AA, Alorainy IA, Hassan HH, Kentab AY, Van Maldergem L, Othman SA, El-Desouki MI, Elgamal EA
Saudi Med J 2006 Mar;27 Suppl 1:S69-80. PMID: 16532134

Diagnosis

Morava E, Guillard M, Lefeber DJ, Wevers RA
Eur J Hum Genet 2009 Sep;17(9):1099-110. Epub 2009 Apr 29 doi: 10.1038/ejhg.2009.22. PMID: 19401719Free PMC Article
Rajab A, Kornak U, Budde BS, Hoffmann K, Jaeken J, Nürnberg P, Mundlos S
Am J Med Genet A 2008 Apr 15;146A(8):965-76. doi: 10.1002/ajmg.a.32143. PMID: 18348262
Nanda A, Alsaleh QA, Al-Sabah H, Marzouk EE, Salam AM, Nanda M, Anim JT
Pediatr Dermatol 2008 Jan-Feb;25(1):66-71. doi: 10.1111/j.1525-1470.2007.00586.x. PMID: 18304158
Al-Gazali LI, Sztriha L, Skaff F, Haas D
Am J Med Genet 2001 Jul 1;101(3):213-20. doi: 10.1002/ajmg.1352. PMID: 11424136
Hurvitz SA, Baumgarten A, Goodman RM
Clin Genet 1990 Oct;38(4):307-13. doi: 10.1111/j.1399-0004.1990.tb03585.x. PMID: 2268976

Therapy

Myung DB, Lee JH, Han HS, Lee KY, Ahn HS, Shin YK, Song E, Kim BH, Lee KH, Lee SH, Lee KT
Nutrients 2020 May 28;12(6) doi: 10.3390/nu12061588. PMID: 32481760Free PMC Article

Prognosis

Dimopoulou A, Fischer B, Gardeitchik T, Schröter P, Kayserili H, Schlack C, Li Y, Brum JM, Barisic I, Castori M, Spaich C, Fletcher E, Mahayri Z, Bhat M, Girisha KM, Lachlan K, Johnson D, Phadke S, Gupta N, Simandlova M, Kabra M, David A, Nijtmans L, Chitayat D, Tuysuz B, Brancati F, Mundlos S, Van Maldergem L, Morava E, Wollnik B, Kornak U
Mol Genet Metab 2013 Nov;110(3):352-61. Epub 2013 Aug 24 doi: 10.1016/j.ymgme.2013.08.009. PMID: 24035636
Skidmore DL, Chitayat D, Morgan T, Hinek A, Fischer B, Dimopoulou A, Somers G, Halliday W, Blaser S, Diambomba Y, Lemire EG, Kornak U, Robertson SP
Am J Med Genet A 2011 Aug;155A(8):1848-56. Epub 2011 Jul 7 doi: 10.1002/ajmg.a.34057. PMID: 21739576
Morava E, Guillard M, Lefeber DJ, Wevers RA
Eur J Hum Genet 2009 Sep;17(9):1099-110. Epub 2009 Apr 29 doi: 10.1038/ejhg.2009.22. PMID: 19401719Free PMC Article
Nanda A, Alsaleh QA, Al-Sabah H, Marzouk EE, Salam AM, Nanda M, Anim JT
Pediatr Dermatol 2008 Jan-Feb;25(1):66-71. doi: 10.1111/j.1525-1470.2007.00586.x. PMID: 18304158

Clinical prediction guides

Dimopoulou A, Fischer B, Gardeitchik T, Schröter P, Kayserili H, Schlack C, Li Y, Brum JM, Barisic I, Castori M, Spaich C, Fletcher E, Mahayri Z, Bhat M, Girisha KM, Lachlan K, Johnson D, Phadke S, Gupta N, Simandlova M, Kabra M, David A, Nijtmans L, Chitayat D, Tuysuz B, Brancati F, Mundlos S, Van Maldergem L, Morava E, Wollnik B, Kornak U
Mol Genet Metab 2013 Nov;110(3):352-61. Epub 2013 Aug 24 doi: 10.1016/j.ymgme.2013.08.009. PMID: 24035636
Skidmore DL, Chitayat D, Morgan T, Hinek A, Fischer B, Dimopoulou A, Somers G, Halliday W, Blaser S, Diambomba Y, Lemire EG, Kornak U, Robertson SP
Am J Med Genet A 2011 Aug;155A(8):1848-56. Epub 2011 Jul 7 doi: 10.1002/ajmg.a.34057. PMID: 21739576
Nanda A, Alsaleh QA, Al-Sabah H, Marzouk EE, Salam AM, Nanda M, Anim JT
Pediatr Dermatol 2008 Jan-Feb;25(1):66-71. doi: 10.1111/j.1525-1470.2007.00586.x. PMID: 18304158

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