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Blepharophimosis - intellectual disability syndrome, SBBYS type(SBBYSS)

MedGen UID:
350209
Concept ID:
C1863557
Disease or Syndrome
Synonyms: Mental retardation unusual facies hypothyroidism; OHDO SYNDROME, SBBYS VARIANT; Say-Barber-Biesecker Variant of Ohdo Syndrome; SAY-BARBER-BIESECKER-YOUNG-SIMPSON SYNDROME; Say-Barber-Biesecker-Young-Simpson variant of Ohdo Syndrome; SBBYSS; Young Simpson syndrome
SNOMED CT: Say-Barber-Biesecker-Young-Simpson syndrome (699298009); Ohdo syndrome, Say-Barber-Biesecker-Young-Simpson variant (699298009); Blepharophimosis-intellectual deficit syndrome, Say-Barber/Biesecker/Young-Simpson type (699298009); Say-Barber-Biesecker-Young-Simpson variant of Ohdo syndrome (699298009); Young-Simpson syndrome (699298009); Hypothyroidism, dysmorphism, postaxial polydactyly, intellectual disability syndrome (699298009); Blepharophimosis, intellectual disability syndrome, Say-Barber-Biesecker-Young-Simpson type (699298009)
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): KAT6B (10q22.2)
 
Monarch Initiative: MONDO:0011365
OMIM®: 603736
Orphanet: ORPHA3047

Disease characteristics

Excerpted from the GeneReview: KAT6B Disorders
KAT6B disorders include genitopatellar syndrome (GPS) and Say-Barber-Biesecker-Young-Simpson variant of Ohdo syndrome (SBBYSS) which are part of a broad phenotypic spectrum with variable expressivity; individuals presenting with a phenotype intermediate between GPS and SBBYSS have been reported. Both phenotypes are characterized by some degree of global developmental delay / intellectual disability; hypotonia; genital abnormalities; and skeletal abnormalities including patellar hypoplasia/agenesis, flexion contractures of the knees and/or hips, and anomalies of the digits, spine, and/or ribs. Congenital heart defects, small bowel malrotation, feeding difficulties, slow growth, cleft palate, hearing loss, and dental anomalies have been observed in individuals with either phenotype. [from GeneReviews]
Authors:
Gabrielle Lemire  |  Philippe M Campeau  |  Brendan H Lee   view full author information

Additional descriptions

From OMIM
Say-Barber-Biesecker-Young-Simpson syndrome, a variant of Ohdo syndrome (249620), is characterized by distinctive facial appearance with severe blepharophimosis, an immobile mask-like face, a bulbous nasal tip, and a small mouth with a thin upper lip. The condition presents in infancy with severe hypotonia and feeding problems. Associated skeletal problems include joint laxity, abnormally long thumbs and great toes, and dislocated or hypoplastic patellae. Structural cardiac defects are present in around 50% of cases, and dental anomalies, including small and pointed teeth, are common. Many affected individuals have abnormalities of thyroid structure or function. YSS is usually associated with severe mental retardation, delayed motor milestones, and significantly impaired speech (summary by Clayton-Smith et al., 2011). Genitopatellar syndrome (606170) is an allelic disorder with overlapping features.  http://www.omim.org/entry/603736
From MedlinePlus Genetics
The Say-Barber-Biesecker-Young-Simpson (SBBYS) variant of Ohdo syndrome is a rare condition characterized by genital abnormalities in males, missing or underdeveloped kneecaps (patellae), intellectual disability, distinctive facial features, and abnormalities affecting other parts of the body.

Males with the SBBYS variant of Ohdo syndrome typically have undescended testes (cryptorchidism). Females with this condition have normal genitalia.

Missing or underdeveloped patellae is the most common skeletal abnormality associated with the SBBYS variant of Ohdo syndrome. Affected individuals also have joint stiffness involving the hips, knees, and ankles that can impair movement. Although joints in the lower body are stiff, joints in the arms and upper body may be unusually loose (lax). Many people with this condition have long thumbs and first (big) toes.

The SBBYS variant of Ohdo syndrome is also associated with delayed development and intellectual disability, which are often severe. Many affected infants have weak muscle tone (hypotonia) that leads to breathing and feeding difficulties.

The SBBYS variant of Ohdo syndrome is characterized by a mask-like, non-expressive face. Additionally, affected individuals may have distinctive facial features such as prominent cheeks, a broad nasal bridge or a nose with a rounded tip, a narrowing of the eye opening (blepharophimosis), droopy eyelids (ptosis), and abnormalities of the tear (lacrimal) glands. About one-third of affected individuals are born with an opening in the roof of the mouth called a cleft palate. The SBBYS variant of Ohdo syndrome can also be associated with heart defects and dental problems.  https://medlineplus.gov/genetics/condition/ohdo-syndrome-say-barber-biesecker-young-simpson-variant

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).
Hypospadias
MedGen UID:
163083
Concept ID:
C0848558
Congenital Abnormality
Abnormal position of urethral meatus on the ventral penile shaft (underside) characterized by displacement of the urethral meatus from the tip of the glans penis to the ventral surface of the penis, scrotum, or perineum.
Long thumb
MedGen UID:
322130
Concept ID:
C1833148
Finding
Length of the thumb is greater than normal.
Long hallux
MedGen UID:
400514
Concept ID:
C1864375
Finding
Increased length of the big toe.
Primary dilated cardiomyopathy
MedGen UID:
2880
Concept ID:
C0007193
Disease or Syndrome
Familial dilated cardiomyopathy is a genetic form of heart disease. It occurs when heart (cardiac) muscle becomes thin and weakened in at least one chamber of the heart, causing the open area of the chamber to become enlarged (dilated). As a result, the heart is unable to pump blood as efficiently as usual. To compensate, the heart attempts to increase the amount of blood being pumped through the heart, leading to further thinning and weakening of the cardiac muscle. Over time, this condition results in heart failure.\n\nIt usually takes many years for symptoms of familial dilated cardiomyopathy to cause health problems. They typically begin in mid-adulthood, but can occur at any time from infancy to late adulthood. Signs and symptoms of familial dilated cardiomyopathy can include an irregular heartbeat (arrhythmia), shortness of breath (dyspnea), extreme tiredness (fatigue), fainting episodes (syncope), and swelling of the legs and feet. In some cases, the first sign of the disorder is sudden cardiac death. The severity of the condition varies among affected individuals, even in members of the same family.
Feeding difficulties
MedGen UID:
65429
Concept ID:
C0232466
Finding
Impaired ability to eat related to problems gathering food and getting ready to suck, chew, or swallow it.
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.
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).
Hearing impairment
MedGen UID:
235586
Concept ID:
C1384666
Disease or Syndrome
A decreased magnitude of the sensory perception of sound.
Intellectual disability, severe
MedGen UID:
48638
Concept ID:
C0036857
Mental or Behavioral Dysfunction
Severe mental retardation is defined as an intelligence quotient (IQ) in the range of 20-34.
Motor delay
MedGen UID:
381392
Concept ID:
C1854301
Finding
A type of Developmental delay characterized by a delay in acquiring motor skills.
Micrognathia
MedGen UID:
44428
Concept ID:
C0025990
Congenital Abnormality
Developmental hypoplasia of the mandible.
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.
Patellar dislocation
MedGen UID:
253896
Concept ID:
C1135812
Injury or Poisoning
The kneecap normally is located within the groove termed trochlea on the distal femur and can slide up and down in it. Patellar dislocation occurs if the patella fully dislocates out of the groove.
Prominent occiput
MedGen UID:
381255
Concept ID:
C1853737
Finding
Increased convexity of the occiput (posterior part of the skull).
Microcephaly
MedGen UID:
1644158
Concept ID:
C4551563
Finding
Head circumference below 2 standard deviations below the mean for age and gender.
Blepharophimosis
MedGen UID:
2670
Concept ID:
C0005744
Anatomical Abnormality
A fixed reduction in the vertical distance between the upper and lower eyelids with short palpebral fissures.
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.
Bulbous nose
MedGen UID:
66013
Concept ID:
C0240543
Finding
Increased volume and globular shape of the anteroinferior aspect of the nose.
Epicanthus inversus
MedGen UID:
224913
Concept ID:
C1303003
Finding
A fold of skin starting at or just below the medial aspect of the lower lid and arching upward to cover, extend in front of and lateral to the medial canthus.
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.
Thin upper lip vermilion
MedGen UID:
355352
Concept ID:
C1865017
Finding
Height of the vermilion of the upper lip in the midline more than 2 SD below the mean. Alternatively, an apparently reduced height of the vermilion of the upper lip in the frontal view (subjective).
Cleft palate
MedGen UID:
756015
Concept ID:
C2981150
Congenital Abnormality
Cleft palate is a developmental defect of the palate resulting from a failure of fusion of the palatine processes and manifesting as a separation of the roof of the mouth (soft and hard palate).
Hypothyroidism
MedGen UID:
6991
Concept ID:
C0020676
Disease or Syndrome
Deficiency of thyroid hormone.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVBlepharophimosis - intellectual disability syndrome, SBBYS type
Follow this link to review classifications for Blepharophimosis - intellectual disability syndrome, SBBYS type in Orphanet.

Recent clinical studies

Etiology

Klaniewska M, Bolanowska-Tyszko A, Latos-Bielenska A, Jezela-Stanek A, Szczaluba K, Krajewska-Walasek M, Ciara E, Pelc M, Jurkiewicz D, Stawinski P, Zubkiewicz-Kucharska A, Rydzanicz M, Ploski R, Smigiel R
Mol Genet Genomic Med 2023 Dec;11(12):e2265. Epub 2023 Sep 1 doi: 10.1002/mgg3.2265. PMID: 37658610Free PMC Article
Szakszon K, Salpietro C, Kakar N, Knegt AC, Oláh É, Dallapiccola B, Borck G
Am J Med Genet A 2013 Apr;161A(4):884-8. Epub 2013 Feb 22 doi: 10.1002/ajmg.a.35848. PMID: 23436491
Verloes A, Bremond-Gignac D, Isidor B, David A, Baumann C, Leroy MA, Stevens R, Gillerot Y, Héron D, Héron B, Benzacken B, Lacombe D, Brunner H, Bitoun P
Am J Med Genet A 2006 Jun 15;140(12):1285-96. doi: 10.1002/ajmg.a.31270. PMID: 16700052

Diagnosis

Davarnia B, Panahi M, Rahimi B, Anari H, Farajollahi R, Rodbaneh EA, Jeddi F
J Med Case Rep 2024 Jan 5;18(1):4. doi: 10.1186/s13256-023-04237-w. PMID: 38178270Free PMC Article
Merritt J, Hart JC, LeGrow TL
BMJ Case Rep 2017 Jul 14;2017 doi: 10.1136/bcr-2017-219930. PMID: 28710305Free PMC Article
Szakszon K, Salpietro C, Kakar N, Knegt AC, Oláh É, Dallapiccola B, Borck G
Am J Med Genet A 2013 Apr;161A(4):884-8. Epub 2013 Feb 22 doi: 10.1002/ajmg.a.35848. PMID: 23436491
Verloes A, Bremond-Gignac D, Isidor B, David A, Baumann C, Leroy MA, Stevens R, Gillerot Y, Héron D, Héron B, Benzacken B, Lacombe D, Brunner H, Bitoun P
Am J Med Genet A 2006 Jun 15;140(12):1285-96. doi: 10.1002/ajmg.a.31270. PMID: 16700052

Prognosis

Klaniewska M, Bolanowska-Tyszko A, Latos-Bielenska A, Jezela-Stanek A, Szczaluba K, Krajewska-Walasek M, Ciara E, Pelc M, Jurkiewicz D, Stawinski P, Zubkiewicz-Kucharska A, Rydzanicz M, Ploski R, Smigiel R
Mol Genet Genomic Med 2023 Dec;11(12):e2265. Epub 2023 Sep 1 doi: 10.1002/mgg3.2265. PMID: 37658610Free PMC Article
Yilmaz R, Beleza-Meireles A, Price S, Oliveira R, Kubisch C, Clayton-Smith J, Szakszon K, Borck G
Am J Med Genet A 2015 Dec;167A(12):3006-10. Epub 2015 Sep 3 doi: 10.1002/ajmg.a.37343. PMID: 26334766
Verloes A, Bremond-Gignac D, Isidor B, David A, Baumann C, Leroy MA, Stevens R, Gillerot Y, Héron D, Héron B, Benzacken B, Lacombe D, Brunner H, Bitoun P
Am J Med Genet A 2006 Jun 15;140(12):1285-96. doi: 10.1002/ajmg.a.31270. PMID: 16700052

Clinical prediction guides

Davarnia B, Panahi M, Rahimi B, Anari H, Farajollahi R, Rodbaneh EA, Jeddi F
J Med Case Rep 2024 Jan 5;18(1):4. doi: 10.1186/s13256-023-04237-w. PMID: 38178270Free PMC Article
Yilmaz R, Beleza-Meireles A, Price S, Oliveira R, Kubisch C, Clayton-Smith J, Szakszon K, Borck G
Am J Med Genet A 2015 Dec;167A(12):3006-10. Epub 2015 Sep 3 doi: 10.1002/ajmg.a.37343. PMID: 26334766

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