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Beare-Stevenson cutis gyrata syndrome(BSTVS)

MedGen UID:
377668
Concept ID:
C1852406
Disease or Syndrome
Synonyms: Beare-Stevenson Syndrome; BSTVS; Cutis Gyrata syndrome of Beare and Stevenson
SNOMED CT: Cutis gyrata syndrome of Beare and Stevenson (703528008); Beare-Stevenson cutis gyrata syndrome (703528008); Cutis gyrata, acanthosis nigricans, craniosynostosis syndrome (703528008)
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): FGFR2 (10q26.13)
 
Monarch Initiative: MONDO:0007412
OMIM®: 123790
Orphanet: ORPHA1555

Definition

Beare-Stevenson cutis gyrata syndrome (BSTVS) is an autosomal dominant condition characterized by the furrowed skin disorder of cutis gyrata, acanthosis nigricans, craniosynostosis, craniofacial dysmorphism, digital anomalies, umbilical and anogenital abnormalities, and early death (summary by Przylepa et al., 1996). [from OMIM]

Additional description

From MedlinePlus Genetics
Beare-Stevenson cutis gyrata syndrome is a genetic disorder that typically features skin abnormalities and the premature fusion of certain bones of the skull (craniosynostosis). This early fusion prevents the skull from growing normally and affects the shape of the head and face.

Many of the characteristic facial features of Beare-Stevenson cutis gyrata syndrome result from the premature fusion of the skull bones. The head is unable to grow normally, which leads to a cloverleaf-shaped skull, wide-set and bulging eyes, ear abnormalities, and an underdeveloped upper jaw. Early fusion of the skull bones also affects the growth of the brain, causing delayed development and intellectual disability.

A skin abnormality called cutis gyrata is also characteristic of this disorder. The skin has a furrowed and wrinkled appearance, particularly on the face, near the ears, and on the palms and soles of the feet. Additionally, thick, dark, velvety areas of skin (acanthosis nigricans) are sometimes found on the hands and feet and in the genital region.

Additional signs and symptoms of Beare-Stevenson cutis gyrata syndrome can include a blockage of the nasal passages (choanal atresia), a malformation of the airways (tracheal cartilaginous sleeve), overgrowth of the umbilical stump (tissue that normally falls off shortly after birth, leaving the belly button), and abnormalities of the genitalia and anus. The medical complications associated with this condition are often life-threatening in infancy or early childhood.  https://medlineplus.gov/genetics/condition/beare-stevenson-cutis-gyrata-syndrome

Clinical features

From HPO
Acanthosis nigricans
MedGen UID:
54
Concept ID:
C0000889
Disease or Syndrome
A dermatosis characterized by thickened, hyperpigmented plaques, typically on the intertriginous surfaces and neck.
Chiari malformation
MedGen UID:
2065
Concept ID:
C0003803
Congenital Abnormality
Chiari malformation consists of a downward displacement of the cerebellar tonsils and the medulla through the foramen magnum, sometimes causing hydrocephalus as a result of obstruction of CSF outflow.
Ptosis
MedGen UID:
2287
Concept ID:
C0005745
Disease or Syndrome
The upper eyelid margin is positioned 3 mm or more lower than usual and covers the superior portion of the iris (objective); or, the upper lid margin obscures at least part of the pupil (subjective).
Choanal atresia
MedGen UID:
3395
Concept ID:
C0008297
Congenital Abnormality
Absence or abnormal closure of the choana (the posterior nasal aperture). Most embryologists believe that posterior choanal atresia results from a failure of rupture between the 35th and 38th day of fetal life of the partition which separates the bucconasal or buccopharyngeal membranes. The resultant choanal atresia may be unilateral or bilateral, bony or membranous, complete or incomplete. In over 90 per cent of cases the obstruction is bony, while in the remainder it is membranous. The bony type of atresia is commonly located 1-2 mm. anterior to the posterior edge of the hard palate, and the osseous septum varies in thickness from 1 to 10 mm. In the membranous form of choanal atresia the obstruction usually occurs further posteriorly. In approximately one third of cases the atresia is bilateral.
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.
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.
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.
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).
Hypertensive disorder
MedGen UID:
6969
Concept ID:
C0020538
Disease or Syndrome
The presence of chronic increased pressure in the systemic arterial system.
Narrow mouth
MedGen UID:
44435
Concept ID:
C0026034
Congenital Abnormality
Distance between the commissures of the mouth more than 2 SD below the mean. Alternatively, an apparently decreased width of the oral aperture (subjective).
Optic atrophy
MedGen UID:
18180
Concept ID:
C0029124
Disease or Syndrome
Atrophy of the optic nerve. Optic atrophy results from the death of the retinal ganglion cell axons that comprise the optic nerve and manifesting as a pale optic nerve on fundoscopy.
Skin tags
MedGen UID:
11452
Concept ID:
C0037293
Neoplastic Process
Cutaneous skin tags also known as acrochorda or fibroepithelial polyps are small benign tumours that may either form secondarily over time primarily in areas where the skin forms creases, such as the neck, armpit or groin or may also be present at birth, in which case they usually occur in the periauricular region.
Corpus callosum, agenesis of
MedGen UID:
104498
Concept ID:
C0175754
Congenital Abnormality
The corpus callosum is the largest fiber tract in the central nervous system and the major interhemispheric fiber bundle in the brain. Formation of the corpus callosum begins as early as 6 weeks' gestation, with the first fibers crossing the midline at 11 to 12 weeks' gestation, and completion of the basic shape by age 18 to 20 weeks (Schell-Apacik et al., 2008). Agenesis of the corpus callosum (ACC) is one of the most frequent malformations in brain with a reported incidence ranging between 0.5 and 70 in 10,000 births. ACC is a clinically and genetically heterogeneous condition, which can be observed either as an isolated condition or as a manifestation in the context of a congenital syndrome (see MOLECULAR GENETICS and Dobyns, 1996). Also see mirror movements-1 and/or agenesis of the corpus callosum (MRMV1; 157600). Schell-Apacik et al. (2008) noted that there is confusion in the literature regarding radiologic terminology concerning partial absence of the corpus callosum, where various designations have been used, including hypogenesis, hypoplasia, partial agenesis, or dysgenesis.
Cutis gyrata of scalp
MedGen UID:
78095
Concept ID:
C0263417
Disease or Syndrome
The presence of convoluted folds and furrows formed from thickened skin of the scalp, resembling cerebriform pattern. The scalp has convoluted and elevated folds, 1 to 2 cm in thickness. The convolutions generally cannot be flattened by traction.
Small nail
MedGen UID:
537942
Concept ID:
C0263523
Finding
A nail that is diminished in length and width, i.e., underdeveloped nail.
Bifid scrotum
MedGen UID:
90968
Concept ID:
C0341787
Congenital Abnormality
Midline indentation or cleft of the scrotum.
Downslanted palpebral fissures
MedGen UID:
98391
Concept ID:
C0423110
Finding
The palpebral fissure inclination is more than two standard deviations below the mean.
Posteriorly rotated ears
MedGen UID:
96566
Concept ID:
C0431478
Congenital Abnormality
A type of abnormal location of the ears in which the position of the ears is characterized by posterior rotation (the superior part of the ears is rotated towards the back of the head, and the inferior part of the ears towards the front).
Respiratory distress
MedGen UID:
96907
Concept ID:
C0476273
Sign or Symptom
Respiratory distress is objectively observable as the physical or emotional consequences from the experience of dyspnea. The physical presentation of respiratory distress is generally referred to as labored breathing, while the sensation of respiratory distress is called shortness of breath or dyspnea.
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.
Hypoplastic labia majora
MedGen UID:
107566
Concept ID:
C0566899
Finding
Undergrowth of the outer labia.
Choanal stenosis
MedGen UID:
108427
Concept ID:
C0584837
Finding
Abnormal narrowing of the choana (the posterior nasal aperture).
Narrow palate
MedGen UID:
278045
Concept ID:
C1398312
Finding
Width of the palate more than 2 SD below the mean (objective) or apparently decreased palatal width (subjective).
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.
Anteriorly placed anus
MedGen UID:
333160
Concept ID:
C1838705
Finding
Anterior malposition of the anus.
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).
Redundant neck skin
MedGen UID:
374440
Concept ID:
C1840319
Finding
Excess skin around the neck, often lying in horizontal folds.
Prominent scrotal raphe
MedGen UID:
343801
Concept ID:
C1852407
Finding
Increased size of the ridge of tissue that extends along the midline of the scrotum.
Preauricular skin furrow
MedGen UID:
377670
Concept ID:
C1852411
Finding
A groove of the skin immediately in front of the ear.
Midface retrusion
MedGen UID:
339938
Concept ID:
C1853242
Anatomical Abnormality
Posterior positions and/or vertical shortening of the infraorbital and perialar regions, or increased concavity of the face and/or reduced nasolabial angle.
Palmoplantar cutis laxa
MedGen UID:
341602
Concept ID:
C1856714
Finding
Loose, wrinkled skin of hands and feet.
Hypoplastic fingernail
MedGen UID:
347304
Concept ID:
C1856786
Finding
Underdevelopment of a fingernail.
Low-set, posteriorly rotated ears
MedGen UID:
387834
Concept ID:
C1857486
Finding
Ears that are low-set and posteriorly rotated.
Malar flattening
MedGen UID:
347616
Concept ID:
C1858085
Finding
Underdevelopment of the malar prominence of the jugal bone (zygomatic bone in mammals), appreciated in profile, frontal view, and/or by palpation.
Cloverleaf skull
MedGen UID:
348010
Concept ID:
C1860050
Finding
Trilobar skull configuration when viewed from the front or behind.
Limited elbow extension
MedGen UID:
401158
Concept ID:
C1867103
Finding
Limited ability to straighten the arm at the elbow joint.
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.
Ventriculomegaly
MedGen UID:
480553
Concept ID:
C3278923
Finding
An increase in size of the ventricular system of the brain.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
Follow this link to review classifications for Beare-Stevenson cutis gyrata syndrome in Orphanet.

Professional guidelines

PubMed

Lam AS, Liu CC, Deutsch GH, Rivera J, Perkins JA, Holmes G, Jabs EW, Cunningham ML, Dahl JP
Laryngoscope 2021 Apr;131(4):E1349-E1356. Epub 2020 Sep 4 doi: 10.1002/lary.29060. PMID: 32886384Free PMC Article

Recent clinical studies

Etiology

Wenger TL, Bhoj EJ, Wetmore RF, Mennuti MT, Bartlett SP, Mollen TJ, McDonald-McGinn DM, Zackai EH
Am J Med Genet A 2015 Apr;167A(4):852-7. Epub 2015 Feb 23 doi: 10.1002/ajmg.a.36985. PMID: 25706251
Too CW, Tang PH
Ann Acad Med Singap 2009 Sep;38(9):832-4. PMID: 19816645
Nishimoto S, Oyama T, Nagashima T, Osaki Y, Yoshimura Y, Fukuda K, Kawai K, Tsumano T, Kakibuchi M
J Craniofac Surg 2008 Nov;19(6):1622-7. doi: 10.1097/SCS.0b013e31818b494e. PMID: 19098565

Diagnosis

Wenger TL, Bhoj EJ, Wetmore RF, Mennuti MT, Bartlett SP, Mollen TJ, McDonald-McGinn DM, Zackai EH
Am J Med Genet A 2015 Apr;167A(4):852-7. Epub 2015 Feb 23 doi: 10.1002/ajmg.a.36985. PMID: 25706251
Wang TJ, Hung KS, Chen PK, Chuang WL, Shih TY, Lai BJ, Hsiao M
Acta Neurochir (Wien) 2002 Jul;144(7):743-5. doi: 10.1007/s00701-002-0933-6. PMID: 12181710
Hsu TY, Chang SY, Wang TJ, Ou CY, Chen ZH, Hsu PH
Prenat Diagn 2001 Aug;21(8):665-7. doi: 10.1002/pd.136. PMID: 11536267
Ito S, Matsui K, Ohsaki E, Goto A, Takagi K, Koresawa M, Ito S, Sekido K, Suzuki M, Torikai K, Aida N
Brain Dev 1996 Jul-Aug;18(4):307-11. doi: 10.1016/0387-7604(96)00020-4. PMID: 8879651

Prognosis

Wenger TL, Bhoj EJ, Wetmore RF, Mennuti MT, Bartlett SP, Mollen TJ, McDonald-McGinn DM, Zackai EH
Am J Med Genet A 2015 Apr;167A(4):852-7. Epub 2015 Feb 23 doi: 10.1002/ajmg.a.36985. PMID: 25706251
Nishimoto S, Oyama T, Nagashima T, Osaki Y, Yoshimura Y, Fukuda K, Kawai K, Tsumano T, Kakibuchi M
J Craniofac Surg 2008 Nov;19(6):1622-7. doi: 10.1097/SCS.0b013e31818b494e. PMID: 19098565
Ito S, Matsui K, Ohsaki E, Goto A, Takagi K, Koresawa M, Ito S, Sekido K, Suzuki M, Torikai K, Aida N
Brain Dev 1996 Jul-Aug;18(4):307-11. doi: 10.1016/0387-7604(96)00020-4. PMID: 8879651

Clinical prediction guides

Hall BD, Cadle RG, Golabi M, Morris CA, Cohen MM Jr
Am J Med Genet 1992 Sep 1;44(1):82-9. doi: 10.1002/ajmg.1320440120. PMID: 1519658

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