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Hypertrichotic osteochondrodysplasia Cantu type

MedGen UID:
208647
Concept ID:
C0795905
Disease or Syndrome
Synonyms: Cantu syndrome; Hypertrichotic osteochondrodysplasia
SNOMED CT: Cantu syndrome (239087008); Cantu's syndrome (239087008)
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.
Not genetically inherited
MedGen UID:
988794
Concept ID:
CN307044
Finding
Source: Orphanet
clinical entity without genetic inheritance.
 
Gene (location): ABCC9 (12p12.1)
 
Monarch Initiative: MONDO:0009406
OMIM®: 239850
Orphanet: ORPHA1517

Disease characteristics

Excerpted from the GeneReview: Cantú Syndrome
Cantú syndrome is characterized by congenital hypertrichosis; distinctive coarse facial features (including broad nasal bridge, wide mouth with full lips and macroglossia); enlarged heart with enhanced systolic function or pericardial effusion and in many, a large patent ductus arteriosus (PDA) requiring repair; and skeletal abnormalities (thickening of the calvaria, broad ribs, scoliosis, and flaring of the metaphyses). Other cardiovascular abnormalities may include dilated aortic root and ascending aorta with rare aortic aneurysm, tortuous vascularity involving brain and retinal vasculature, and pulmonary arteriovenous communications. Generalized edema (which may be present at birth) spontaneously resolves; peripheral edema of the lower extremities (and sometimes arms and hands) may develop at adolescence. Developmental delays are common, but intellect is typically normal; behavioral problems can include attention-deficit/hyperactivity disorder, autism spectrum disorder, obsessive-compulsive disorder, anxiety, and depression. [from GeneReviews]
Authors:
Dorothy K Grange  |  Colin G Nichols  |  Gautam K Singh   view full author information

Additional descriptions

From OMIM
Cantu syndrome is a rare disorder characterized by congenital hypertrichosis, neonatal macrosomia, a distinct osteochondrodysplasia, and cardiomegaly. The hypertrichosis leads to thick scalp hair which extends onto the forehead and to a general increase in body hair. Some features are suggestive of a storage disorder, including macrocephaly and coarse facial features, with a broad nasal bridge, epicanthal folds, wide mouth, and full lips. About half of affected individuals are macrosomic and edematous at birth, whereas in childhood they usually have a muscular appearance with little subcutaneous fat. Thickened calvarium, narrow thorax, wide ribs, flattened or ovoid vertebral bodies, coxa valga, osteopenia, enlarged medullary canals, and metaphyseal widening of long bones have been reported. Cardiac manifestations such as patent ductus arteriosus, ventricular hypertrophy, pulmonary hypertension, and pericardial effusions are present in approximately 80% of cases. Motor development is usually delayed due to hypotonia. Most patients have a mild speech delay, and a small percentage have learning difficulties or intellectual disability (summary by van Bon et al., 2012).  http://www.omim.org/entry/239850
From MedlinePlus Genetics
Cantú syndrome is a rare condition characterized by excess hair growth (hypertrichosis), a distinctive facial appearance, heart defects, and several other abnormalities. The features of the disorder vary among affected individuals.

People with Cantú syndrome have thick scalp hair that extends onto the forehead and grows down onto the cheeks in front of the ears. They also have increased body hair, especially on the back, arms, and legs. Most affected individuals have a large head (macrocephaly) and distinctive facial features that are described as "coarse." These include a broad nasal bridge, skin folds covering the inner corner of the eyes (epicanthal folds), and a wide mouth with full lips. As affected individuals get older, the face lengthens, the chin becomes more prominent, and the eyes become deep-set.

Many infants with Cantú syndrome are born with a heart defect such as an enlarged heart (cardiomegaly) or patent ductus arteriosus (PDA). The ductus arteriosus is a connection between two major arteries, the aorta and the pulmonary artery. This connection is open during fetal development and normally closes shortly after birth. However, the ductus arteriosus remains open, or patent, in babies with PDA. Other heart problems have also been found in people with Cantú syndrome, including an abnormal buildup of fluid around the heart (pericardial effusion) and high blood pressure in the blood vessels that carry blood from the heart to the lungs (pulmonary hypertension).

Additional features of this condition include distinctive skeletal abnormalities, a large body size (macrosomia) at birth, a reduced amount of fat under the skin (subcutaneous fat) beginning in childhood, deep horizontal creases in the palms of the hands and soles of the feet, and an increased susceptibility to respiratory infections. Other signs and symptoms that have been reported include abnormal swelling in the body's tissues (lymphedema), side-to-side curvature of the spine (scoliosis), and reduced bone density (osteopenia). Some affected children have weak muscle tone (hypotonia) that delays the development of motor skills such as sitting, standing, and walking. Most have mildly delayed speech, and some affected children have mild intellectual disability or learning problems.  https://medlineplus.gov/genetics/condition/cantu-syndrome

Clinical features

From HPO
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).
Erlenmeyer flask deformity of the femurs
MedGen UID:
383796
Concept ID:
C1855895
Finding
Flaring of distal femur.
Broad first metatarsal
MedGen UID:
341001
Concept ID:
C1855899
Finding
Increased side-to-side width of the first metatarsal bone.
Short hallux
MedGen UID:
400890
Concept ID:
C1865992
Finding
Underdevelopment (hypoplasia) of the big toe.
Broad hallux
MedGen UID:
401165
Concept ID:
C1867131
Finding
Visible increase in width of the hallux without an increase in the dorso-ventral dimension.
Patent ductus arteriosus
MedGen UID:
4415
Concept ID:
C0013274
Congenital Abnormality
In utero, the ductus arteriosus (DA) serves to divert ventricular output away from the lungs and toward the placenta by connecting the main pulmonary artery to the descending aorta. A patent ductus arteriosus (PDA) in the first 3 days of life is a physiologic shunt in healthy term and preterm newborn infants, and normally is substantially closed within about 24 hours after bith and completely closed after about three weeks. Failure of physiologcal closure is referred to a persistent or patent ductus arteriosus (PDA). Depending on the degree of left-to-right shunting, PDA can have clinical consequences.
Cardiomegaly
MedGen UID:
5459
Concept ID:
C0018800
Finding
Increased size of the heart, clinically defined as an increased transverse diameter of the cardiac silhouette that is greater than or equal to 50% of the transverse diameter of the chest (increased cardiothoracic ratio) on a posterior-anterior projection of a chest radiograph or a computed tomography.
Pericardial effusion
MedGen UID:
10653
Concept ID:
C0031039
Disease or Syndrome
Accumulation of fluid within the pericardium.
Bicuspid aortic valve
MedGen UID:
57436
Concept ID:
C0149630
Congenital Abnormality
Aortic valve disease-2 (AOVD2) is characterized by bicuspid aortic valve (BAV) and dilation of the ascending aorta. Calcification of the valve and the aorta has been observed, and some patients exhibit coarctation of the aorta (Tan et al., 2012; Luyckx et al., 2019; Park et al., 2019). For a general phenotypic description and a discussion of genetic heterogeneity of aortic valve disease, see AOVD1 (109730).
Congenital hypertrophy of left ventricle
MedGen UID:
341003
Concept ID:
C1855901
Congenital Abnormality
Large for gestational age
MedGen UID:
341215
Concept ID:
C1848395
Finding
The term large for gestational age applies to babies whose birth weight lies above the 90th percentile for that gestational age.
Intellectual disability, mild
MedGen UID:
10044
Concept ID:
C0026106
Mental or Behavioral Dysfunction
Mild intellectual disability is defined as an intelligence quotient (IQ) in the range of 50-69.
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.
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).
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.
Delayed skeletal maturation
MedGen UID:
108148
Concept ID:
C0541764
Finding
A decreased rate of skeletal maturation. Delayed skeletal maturation can be diagnosed on the basis of an estimation of the bone age from radiographs of specific bones in the human body.
Large sella turcica
MedGen UID:
334811
Concept ID:
C1843677
Finding
An abnormal enlargement of the sella turcica.
Platyspondyly
MedGen UID:
335010
Concept ID:
C1844704
Finding
A flattened vertebral body shape with reduced distance between the vertebral endplates.
Metaphyseal widening
MedGen UID:
341364
Concept ID:
C1849039
Finding
Abnormal widening of the metaphyseal regions of long bones.
Ovoid vertebral bodies
MedGen UID:
344549
Concept ID:
C1855665
Finding
When viewed in lateral radiographs, vertebral bodies have a roughly rectangular configuration. This term applies if the vertebral body appears rounded or oval.
Enlarged posterior fossa
MedGen UID:
340998
Concept ID:
C1855889
Finding
Abnormal increased size of the posterior cranial fossa.
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.
Cuboid-shaped vertebral bodies
MedGen UID:
392973
Concept ID:
C2673653
Finding
Hypoplastic ischiopubic ramus
MedGen UID:
870183
Concept ID:
C4024617
Finding
Underdevelopment of the ischiopubic ramus, which is comprised of the inferior pubic ramus and the inferior ramus of the ischium.
Lymphedema
MedGen UID:
6155
Concept ID:
C0024236
Disease or Syndrome
Localized fluid retention and tissue swelling caused by a compromised lymphatic system.
Gingival overgrowth
MedGen UID:
87712
Concept ID:
C0376480
Finding
Hyperplasia of the gingiva (that is, a thickening of the soft tissue overlying the alveolar ridge. The degree of thickening ranges from involvement of the interdental papillae alone to gingival overgrowth covering the entire tooth crown.
Short neck
MedGen UID:
99267
Concept ID:
C0521525
Finding
Diminished length of the neck.
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).
Depressed nasal bridge
MedGen UID:
373112
Concept ID:
C1836542
Finding
Posterior positioning of the nasal root in relation to the overall facial profile for age.
Prominent forehead
MedGen UID:
373291
Concept ID:
C1837260
Finding
Forward prominence of the entire forehead, due to protrusion of the frontal bone.
Thick lower lip vermilion
MedGen UID:
326567
Concept ID:
C1839739
Finding
Increased thickness of the lower lip, leading to a prominent appearance of the lower lip. The height of the vermilion of the lower lip in the midline is more than 2 SD above the mean. Alternatively, an apparently increased height of the vermilion of the lower lip in the frontal view (subjective).
Anteverted nares
MedGen UID:
326648
Concept ID:
C1840077
Finding
Anteriorly-facing nostrils viewed with the head in the Frankfurt horizontal and the eyes of the observer level with the eyes of the subject. This gives the appearance of an upturned nose (upturned nasal tip).
Coarse facial features
MedGen UID:
335284
Concept ID:
C1845847
Finding
Absence of fine and sharp appearance of brows, nose, lips, mouth, and chin, usually because of rounded and heavy features or thickened skin with or without thickening of subcutaneous and bony tissues.
Thick upper lip vermilion
MedGen UID:
339521
Concept ID:
C1846423
Finding
Height of the vermilion of the upper lip in the midline more than 2 SD above the mean. Alternatively, an apparently increased height of the vermilion of the upper lip in the frontal view (subjective).
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.
Long eyelashes
MedGen UID:
342955
Concept ID:
C1853738
Finding
Mid upper eyelash length >10 mm or increased length of the eyelashes (subjective).
Curly eyelashes
MedGen UID:
382159
Concept ID:
C2673670
Finding
Abnormally curly or curved eyelashes.
Congenital, generalized hypertrichosis
MedGen UID:
1807304
Concept ID:
C5574955
Disease or Syndrome
A confluent, generalized overgrowth of silvery blonde to gray lanugo hair at birth.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVHypertrichotic osteochondrodysplasia Cantu type
Follow this link to review classifications for Hypertrichotic osteochondrodysplasia Cantu type in Orphanet.

Recent clinical studies

Etiology

van Bon BW, Gilissen C, Grange DK, Hennekam RC, Kayserili H, Engels H, Reutter H, Ostergaard JR, Morava E, Tsiakas K, Isidor B, Le Merrer M, Eser M, Wieskamp N, de Vries P, Steehouwer M, Veltman JA, Robertson SP, Brunner HG, de Vries BB, Hoischen A
Am J Hum Genet 2012 Jun 8;90(6):1094-101. Epub 2012 May 17 doi: 10.1016/j.ajhg.2012.04.014. PMID: 22608503Free PMC Article

Diagnosis

Gao J, McClenaghan C, Matreyek KA, Grange DK, Nichols CG
J Pharmacol Exp Ther 2023 Sep;386(3):298-309. Epub 2023 Aug 1 doi: 10.1124/jpet.123.001659. PMID: 37527933Free PMC Article
Houtman MJC, Chen X, Qile M, Duran K, van Haaften G, Stary-Weinzinger A, van der Heyden MAG
J Cell Mol Med 2019 Aug;23(8):4962-4969. Epub 2019 May 22 doi: 10.1111/jcmm.14329. PMID: 31119887Free PMC Article
Kharade SV, Nichols C, Denton JS
Future Med Chem 2016 May;8(7):789-802. Epub 2016 May 10 doi: 10.4155/fmc-2016-0005. PMID: 27161588Free PMC Article
Cooper PE, Reutter H, Woelfle J, Engels H, Grange DK, van Haaften G, van Bon BW, Hoischen A, Nichols CG
Hum Mutat 2014 Jul;35(7):809-13. Epub 2014 May 6 doi: 10.1002/humu.22555. PMID: 24700710Free PMC Article
van Bon BW, Gilissen C, Grange DK, Hennekam RC, Kayserili H, Engels H, Reutter H, Ostergaard JR, Morava E, Tsiakas K, Isidor B, Le Merrer M, Eser M, Wieskamp N, de Vries P, Steehouwer M, Veltman JA, Robertson SP, Brunner HG, de Vries BB, Hoischen A
Am J Hum Genet 2012 Jun 8;90(6):1094-101. Epub 2012 May 17 doi: 10.1016/j.ajhg.2012.04.014. PMID: 22608503Free PMC Article

Therapy

Kharade SV, Nichols C, Denton JS
Future Med Chem 2016 May;8(7):789-802. Epub 2016 May 10 doi: 10.4155/fmc-2016-0005. PMID: 27161588Free PMC Article

Clinical prediction guides

Hanson A, McClenaghan C, Weng KC, Colijn S, Stratman AN, Halabi CM, Grange DK, Silva JR, Nichols CG
Function (Oxf) 2024 Sep 10;5(5) doi: 10.1093/function/zqae027. PMID: 38984978Free PMC Article
Davis MJ, Kim HJ, Zawieja SD, Castorena-Gonzalez JA, Gui P, Li M, Saunders BT, Zinselmeyer BH, Randolph GJ, Remedi MS, Nichols CG
J Physiol 2020 Aug;598(15):3107-3127. Epub 2020 May 30 doi: 10.1113/JP279612. PMID: 32372450Free PMC Article
Cooper PE, Sala-Rabanal M, Lee SJ, Nichols CG
J Gen Physiol 2015 Dec;146(6):527-40. doi: 10.1085/jgp.201511495. PMID: 26621776Free PMC Article

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