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Cutis laxa, X-linked(OHS)

MedGen UID:
82793
Concept ID:
C0268353
Congenital Abnormality
Synonyms: EDS IX; EDS IX (formerly); Ehlers-Danlos syndrome, occipital horn type (formerly); Occipital horn syndrome; OHS
SNOMED CT: Occipital horn syndrome (59399004); Ehlers-Danlos syndrome type 9 X-linked (59399004); Cutis laxa, x-linked (59399004); Ehlers-Danlos syndrome, mental retardation type (59399004); Ehlers-Danlos syndrome, occipital horn type (59399004); Ehlers-Danlos syndrome, x-linked skeletal type (59399004); Ehlers-Danlos syndrome, type 9 (59399004)
Modes of inheritance:
X-linked recessive inheritance
MedGen UID:
375779
Concept ID:
C1845977
Finding
Source: Orphanet
A mode of inheritance that is observed for recessive traits related to a gene encoded on the X chromosome. In the context of medical genetics, X-linked recessive disorders manifest in males (who have one copy of the X chromosome and are thus hemizygotes), but generally not in female heterozygotes who have one mutant and one normal allele.
 
Gene (location): ATP7A (Xq21.1)
 
Monarch Initiative: MONDO:0010572
OMIM®: 304150
Orphanet: ORPHA198

Definition

Occipital horn syndrome (OHS) is a rare connective tissue disorder characterized by hyperelastic and bruisable skin, hernias, bladder diverticula, hyperextensible joints, varicosities, and multiple skeletal abnormalities. The disorder is sometimes accompanied by mild neurologic impairment, and bony abnormalities of the occiput are a common feature, giving rise to the name (summary by Das et al., 1995). [from OMIM]

Additional description

From MedlinePlus Genetics
The X-linked form of cutis laxa is often called occipital horn syndrome. This form of the disorder is considered a mild type of Menkes syndrome, which is a condition that affects copper levels in the body. In addition to sagging and inelastic skin, occipital horn syndrome is characterized by wedge-shaped calcium deposits in a bone at the base of the skull (the occipital bone), coarse hair, and loose joints.

Researchers have described several different forms of cutis laxa. The forms are often distinguished by their pattern of inheritance: autosomal dominant, autosomal recessive, or X-linked. In general, the autosomal recessive forms of cutis laxa tend to be more severe than the autosomal dominant forms, although some people with autosomal dominant cutis laxa are severely affected. In addition to the features described above, people with autosomal recessive cutis laxa can have delayed development, intellectual disability, seizures, problems with movement, or eye or bone abnormalities.

Cutis laxa can also affect connective tissue in other parts of the body, including the heart, blood vessels, intestines, and lungs. The disorder can cause heart problems and abnormal narrowing, bulging, or tearing of critical blood vessels. Affected individuals may have soft out-pouchings in the lower abdomen (inguinal hernia) or around the belly button (umbilical hernia). Sacs called diverticula can also develop in the walls of certain organs, such as the bladder and intestines. During childhood, some people with cutis laxa develop a life-long lung disease called emphysema, which can make it difficult to breathe. Depending on which organs and tissues are affected, the signs and symptoms of cutis laxa can range from mild to life-threatening.

Other rare conditions, including arterial tortuosity syndrome, geroderma osteodysplastica, and RIN2 syndrome, are sometimes classified as cutis laxa-related conditions, because affected individuals can have loose, sagging skin. These conditions each have a particular pattern of signs and symptoms affecting different tissues and body systems.

The term "cutis laxa" is Latin for loose or lax skin, and this condition is characterized by skin that is sagging and not stretchy (inelastic). The skin often hangs in loose folds, causing the face and other parts of the body to have a droopy or wrinkled appearance. Extremely wrinkled skin may be particularly noticeable on the neck and in the armpits and groin.

Cutis laxa is a disorder of connective tissue, which is the tissue that provides structure and strength to the muscles, joints, organs, and skin. Most cases are inherited, but some are acquired, which means they do not appear to be caused by genetic variations. While signs and symptoms of inherited cutis laxa are often noticeable in infancy or childhood, acquired cutis laxa typically appears later in life. This summary primarily describes inherited forms of cutis laxa.    https://medlineplus.gov/genetics/condition/cutis-laxa

Clinical features

From HPO
Urinary bladder carcinoma
MedGen UID:
147071
Concept ID:
C0699885
Neoplastic Process
Bladder cancer is a disease in which certain cells in the bladder become abnormal and multiply uncontrollably to form a tumor. The bladder is a muscular organ in the lower abdomen that stores urine until it can be removed (excreted) from the body.\n\nBladder cancer may cause blood in the urine, pain during urination, frequent urination, the feeling of needing to urinate without being able to, or lower back pain. Many of these signs and symptoms are nonspecific, which means they may occur in multiple disorders. People who have one or more of these nonspecific health problems often do not have bladder cancer, but have another condition such as an infection.\n\nBladder cancer develops when tumors form in the tissue that lines the bladder. There are several types of bladder cancer, categorized by the type of cell in the tissue that becomes cancerous. The most common type is transitional cell carcinoma (also known as urothelial carcinoma); others include squamous cell carcinoma and adenocarcinoma. If the tumor spreads  (metastasizes) beyond the lining of the bladder into nearby tissues or organs, it is known as invasive bladder cancer. 
Hydronephrosis
MedGen UID:
42531
Concept ID:
C0020295
Disease or Syndrome
Severe distention of the kidney with dilation of the renal pelvis and calices.
Ureteral obstruction
MedGen UID:
12012
Concept ID:
C0041956
Disease or Syndrome
Obstruction of the flow of urine through the ureter.
Diverticulum of bladder
MedGen UID:
57625
Concept ID:
C0156273
Finding
Diverticulum (sac or pouch) in the wall of the urinary bladder.
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.
Coxa valga
MedGen UID:
116080
Concept ID:
C0239137
Finding
Coxa valga is a deformity of the hip in which the angle between the femoral shaft and the femoral neck is increased compared to age-adjusted values (about 150 degrees in newborns gradually reducing to 120-130 degrees in adults).
Genu valgum
MedGen UID:
154364
Concept ID:
C0576093
Anatomical Abnormality
The legs angle inward, such that the knees are close together and the ankles far apart.
Short humerus
MedGen UID:
316907
Concept ID:
C1832117
Congenital Abnormality
Underdevelopment of the humerus.
Limited knee extension
MedGen UID:
336755
Concept ID:
C1844690
Finding
Reduced ability to extend (straighten) the knee joint.
Limited elbow extension
MedGen UID:
401158
Concept ID:
C1867103
Finding
Limited ability to straighten the arm at the elbow joint.
Carotid artery tortuosity
MedGen UID:
724577
Concept ID:
C1303076
Finding
Abnormal tortuous (i.e., twisted) form of the carotid arteries.
Growth delay
MedGen UID:
99124
Concept ID:
C0456070
Pathologic Function
A deficiency or slowing down of growth pre- and postnatally.
Chronic diarrhea
MedGen UID:
96036
Concept ID:
C0401151
Finding
The presence of chronic diarrhea, which is usually taken to mean diarrhea that has persisted for over 4 weeks.
Orthostatic hypotension
MedGen UID:
43803
Concept ID:
C0020651
Disease or Syndrome
A form of hypotension characterized by a sudden fall in blood pressure that occurs when a person assumes a standing position.
Seizure
MedGen UID:
20693
Concept ID:
C0036572
Sign or Symptom
A seizure is an intermittent abnormality of nervous system physiology characterised by a transient occurrence of signs and/or symptoms due to abnormal excessive or synchronous neuronal activity in the brain.
Global developmental delay
MedGen UID:
107838
Concept ID:
C0557874
Finding
A delay in the achievement of motor or mental milestones in the domains of development of a child, including motor skills, speech and language, cognitive skills, and social and emotional skills. This term should only be used to describe children younger than five years of age.
Kyphosis
MedGen UID:
44042
Concept ID:
C0022821
Anatomical Abnormality
Exaggerated anterior convexity of the thoracic vertebral column.
Osteoporosis
MedGen UID:
14535
Concept ID:
C0029456
Disease or Syndrome
Osteoporosis is a systemic skeletal disease characterized by low bone density and microarchitectural deterioration of bone tissue with a consequent increase in bone fragility. According to the WHO criteria, osteoporosis is defined as a BMD that lies 2.5 standard deviations or more below the average value for young healthy adults (a T-score below -2.5 SD).
Pectus carinatum
MedGen UID:
57643
Concept ID:
C0158731
Finding
A deformity of the chest caused by overgrowth of the ribs and characterized by protrusion of the sternum.
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.
Short clavicles
MedGen UID:
96529
Concept ID:
C0426799
Congenital Abnormality
Reduced length of the clavicles.
Broad clavicles
MedGen UID:
98091
Concept ID:
C0426801
Finding
Increased width (cross-sectional diameter) of the clavicles.
Exostoses
MedGen UID:
257035
Concept ID:
C1442903
Disease or Syndrome
An exostosis is a benign growth the projects outward from the bone surface. It is capped by cartilage, and arises from a bone that develops from cartilage.
Pelvic bone exostoses
MedGen UID:
335004
Concept ID:
C1844689
Neoplastic Process
A benign growth the projects outward from the bone surface of the pelvis. Exostoses are capped by cartilage, and arise from a bone that develops from cartilage.
Platyspondyly
MedGen UID:
335010
Concept ID:
C1844704
Finding
A flattened vertebral body shape with reduced distance between the vertebral endplates.
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.
Broad ribs
MedGen UID:
336390
Concept ID:
C1848654
Finding
Increased width of ribs
Persistent open anterior fontanelle
MedGen UID:
376607
Concept ID:
C1849537
Finding
The anterior fontanelle generally ossifies by around the 18th month of life. A persistent open anterior fontanelle is diagnosed if closure is delayed beyond this age.
Capitate-hamate fusion
MedGen UID:
346488
Concept ID:
C1857002
Finding
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.
Hiatus hernia
MedGen UID:
483347
Concept ID:
C3489393
Disease or Syndrome
The presence of a hernia in which the upper part of the stomach, i.e., mainly the gastric cardia protrudes through the diaphragmatic esophageal hiatus.
Decreased circulating ceruloplasmin concentration
MedGen UID:
472980
Concept ID:
C0240997
Finding
Decreased concentration of ceruloplasmin in the blood.
Decreased circulating copper concentration
MedGen UID:
488831
Concept ID:
C0268070
Disease or Syndrome
A reduced concentration of copper in the blood.
High forehead
MedGen UID:
65991
Concept ID:
C0239676
Finding
An abnormally increased height of the forehead.
Convex nasal ridge
MedGen UID:
66809
Concept ID:
C0240538
Finding
Nasal ridge curving anteriorly to an imaginary line that connects the nasal root and tip. The nose appears often also prominent, and the columella low.
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).
Long face
MedGen UID:
324419
Concept ID:
C1836047
Finding
Facial height (length) is more than 2 standard deviations above the mean (objective); or, an apparent increase in the height (length) of the face (subjective).
Narrow face
MedGen UID:
373334
Concept ID:
C1837463
Finding
Bizygomatic (upper face) and bigonial (lower face) width are both more than 2 standard deviations below the mean (objective); or, an apparent reduction in the width of the upper and lower face (subjective).
Long neck
MedGen UID:
333409
Concept ID:
C1839816
Finding
Increased inferior-superior length of the neck.
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.
Hyperextensible skin
MedGen UID:
66023
Concept ID:
C0241074
Finding
A condition in which the skin can be stretched beyond normal, and then returns to its initial position.
Pili torti
MedGen UID:
82670
Concept ID:
C0263491
Finding
Pili (from Latin pilus, hair) torti (from Latin tortus, twisted) refers to short and brittle hairs that appear flattened and twisted when viewed through a microscope.
Coarse hair
MedGen UID:
124454
Concept ID:
C0277959
Finding
Hair shafts are rough in texture.
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.
Redundant skin
MedGen UID:
154379
Concept ID:
C0581342
Pathologic Function
Loose and sagging skin often associated with loss of skin elasticity.
Soft skin
MedGen UID:
336730
Concept ID:
C1844592
Finding
Subjective impression of increased softness upon palpation of the skin.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVCutis laxa, X-linked
Follow this link to review classifications for Cutis laxa, X-linked in Orphanet.

Professional guidelines

PubMed

Kodama H, Fujisawa C, Bhadhprasit W
Curr Drug Metab 2012 Mar;13(3):237-50. doi: 10.2174/138920012799320455. PMID: 21838703Free PMC Article
Kodama H, Murata Y, Kobayashi M
Pediatr Int 1999 Aug;41(4):423-9. doi: 10.1046/j.1442-200x.1999.01095.x. PMID: 10453199

Curated

Tümer Z, Klomp L
Eur J Hum Genet 2011 Oct;19(10) Epub 2011 Apr 13 doi: 10.1038/ejhg.2011.56. PMID: 21487442Free PMC Article

Recent clinical studies

Etiology

De Feyter S, Beyens A, Callewaert B
J Inherit Metab Dis 2023 Mar;46(2):163-173. Epub 2023 Feb 3 doi: 10.1002/jimd.12590. PMID: 36692329
Kodama H, Fujisawa C, Bhadhprasit W
Curr Drug Metab 2012 Mar;13(3):237-50. doi: 10.2174/138920012799320455. PMID: 21838703Free PMC Article
Desai V, Donsante A, Swoboda KJ, Martensen M, Thompson J, Kaler SG
Clin Genet 2011 Feb;79(2):176-82. doi: 10.1111/j.1399-0004.2010.01451.x. PMID: 20497190Free PMC Article
Palmer CA, Percy AK
J Child Neurol 2001 Oct;16(10):764-6. doi: 10.1177/088307380101601011. PMID: 11669352
Jacome DE
Epilepsia 1999 Apr;40(4):467-73. doi: 10.1111/j.1528-1157.1999.tb00742.x. PMID: 10219273

Diagnosis

De Feyter S, Beyens A, Callewaert B
J Inherit Metab Dis 2023 Mar;46(2):163-173. Epub 2023 Feb 3 doi: 10.1002/jimd.12590. PMID: 36692329
Lorincz MT
Handb Clin Neurol 2018;147:279-292. doi: 10.1016/B978-0-444-63233-3.00018-X. PMID: 29325617
Woimant F, Trocello JM
Handb Clin Neurol 2014;120:851-64. doi: 10.1016/B978-0-7020-4087-0.00057-7. PMID: 24365357
Kaler SG
Handb Clin Neurol 2013;113:1745-54. doi: 10.1016/B978-0-444-59565-2.00045-9. PMID: 23622398Free PMC Article
Kaler SG
Nat Rev Neurol 2011 Jan;7(1):15-29. doi: 10.1038/nrneurol.2010.180. PMID: 21221114Free PMC Article

Therapy

Lorincz MT
Handb Clin Neurol 2018;147:279-292. doi: 10.1016/B978-0-444-63233-3.00018-X. PMID: 29325617
Møller LB
J Trace Elem Med Biol 2015;31:173-7. Epub 2014 Aug 8 doi: 10.1016/j.jtemb.2014.07.022. PMID: 25172213
Kaler SG
Handb Clin Neurol 2013;113:1745-54. doi: 10.1016/B978-0-444-59565-2.00045-9. PMID: 23622398Free PMC Article
Desai V, Donsante A, Swoboda KJ, Martensen M, Thompson J, Kaler SG
Clin Genet 2011 Feb;79(2):176-82. doi: 10.1111/j.1399-0004.2010.01451.x. PMID: 20497190Free PMC Article
Kodama H, Murata Y, Kobayashi M
Pediatr Int 1999 Aug;41(4):423-9. doi: 10.1046/j.1442-200x.1999.01095.x. PMID: 10453199

Prognosis

De Feyter S, Beyens A, Callewaert B
J Inherit Metab Dis 2023 Mar;46(2):163-173. Epub 2023 Feb 3 doi: 10.1002/jimd.12590. PMID: 36692329
Kaler SG
Handb Clin Neurol 2013;113:1745-54. doi: 10.1016/B978-0-444-59565-2.00045-9. PMID: 23622398Free PMC Article
Jacome DE
Epilepsia 1999 Apr;40(4):467-73. doi: 10.1111/j.1528-1157.1999.tb00742.x. PMID: 10219273
Mercer JF
Am J Clin Nutr 1998 May;67(5 Suppl):1022S-1028S. doi: 10.1093/ajcn/67.5.1022S. PMID: 9587146
Tümer Z, Horn N
Ann Med 1996 Apr;28(2):121-9. doi: 10.3109/07853899609092936. PMID: 8732640

Clinical prediction guides

De Feyter S, Beyens A, Callewaert B
J Inherit Metab Dis 2023 Mar;46(2):163-173. Epub 2023 Feb 3 doi: 10.1002/jimd.12590. PMID: 36692329
Natera-de Benito D, Sola A, Sousa PR, Boronat S, Expósito-Escudero J, Carrera-García L, Ortez C, Jou C, Muchart J, Rebollo M, Armstrong J, Colomer J, Garcia-Cazorla À, Hoenicka J, Palau F, Nascimento A
Pediatr Neurol 2021 Jun;119:40-44. Epub 2021 Mar 26 doi: 10.1016/j.pediatrneurol.2021.03.005. PMID: 33894639
Møller LB
J Trace Elem Med Biol 2015;31:173-7. Epub 2014 Aug 8 doi: 10.1016/j.jtemb.2014.07.022. PMID: 25172213
Kodama H, Fujisawa C, Bhadhprasit W
Curr Drug Metab 2012 Mar;13(3):237-50. doi: 10.2174/138920012799320455. PMID: 21838703Free PMC Article
Mercer JF
Am J Clin Nutr 1998 May;67(5 Suppl):1022S-1028S. doi: 10.1093/ajcn/67.5.1022S. PMID: 9587146

Recent systematic reviews

De Feyter S, Beyens A, Callewaert B
J Inherit Metab Dis 2023 Mar;46(2):163-173. Epub 2023 Feb 3 doi: 10.1002/jimd.12590. PMID: 36692329

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