U.S. flag

An official website of the United States government

Format

Send to:

Choose Destination

Knobloch syndrome 2(KNO2)

MedGen UID:
1812153
Concept ID:
C5676897
Disease or Syndrome
Synonym: KNO2
 
Gene (location): PAK2 (3q29)
 
Monarch Initiative: MONDO:0100119
OMIM®: 618458

Definition

Knobloch syndrome-2 (KNO2) is characterized by severe vitreoretinal degeneration associated with occipital skull defects, ranging from mild encephalocele to abnormally pigmented hair. Developmental delay may be mild or severe (Antonarakis et al., 2022). For a general phenotypic description and discussion of genetic heterogeneity of Knobloch syndrome, see KNO1 (267750). [from OMIM]

Clinical features

From HPO
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.
Chronic constipation
MedGen UID:
98325
Concept ID:
C0401149
Sign or Symptom
Constipation for longer than three months with fewer than 3 bowel movements per week, straining, lumpy or hard stools, and a sensation of anorectal obstruction or incomplete defecation.
Congenital hypertrophic pyloric stenosis
MedGen UID:
196010
Concept ID:
C0700639
Congenital Abnormality
Pyloric stenosis, also known as infantile hypertrophic pyloric stenosis, is an uncommon condition in infants characterized by abnormal thickening of the pylorus muscles in the stomach leading to gastric outlet obstruction. Clinically infants are well at birth. Then, at 3 to 6 weeks of age, the infants present with projectile vomiting, potentially leading to dehydration and weight loss.
Autism
MedGen UID:
13966
Concept ID:
C0004352
Mental or Behavioral Dysfunction
Autism, the prototypic pervasive developmental disorder (PDD), is usually apparent by 3 years of age. It is characterized by a triad of limited or absent verbal communication, a lack of reciprocal social interaction or responsiveness, and restricted, stereotypic, and ritualized patterns of interests and behavior (Bailey et al., 1996; Risch et al., 1999). 'Autism spectrum disorder,' sometimes referred to as ASD, is a broader phenotype encompassing the less severe disorders Asperger syndrome (see ASPG1; 608638) and pervasive developmental disorder, not otherwise specified (PDD-NOS). 'Broad autism phenotype' includes individuals with some symptoms of autism, but who do not meet the full criteria for autism or other disorders. Mental retardation coexists in approximately two-thirds of individuals with ASD, except for Asperger syndrome, in which mental retardation is conspicuously absent (Jones et al., 2008). Genetic studies in autism often include family members with these less stringent diagnoses (Schellenberg et al., 2006). Levy et al. (2009) provided a general review of autism and autism spectrum disorder, including epidemiology, characteristics of the disorder, diagnosis, neurobiologic hypotheses for the etiology, genetics, and treatment options. Genetic Heterogeneity of Autism Autism is considered to be a complex multifactorial disorder involving many genes. Accordingly, several loci have been identified, some or all of which may contribute to the phenotype. Included in this entry is AUTS1, which has been mapped to chromosome 7q22. Other susceptibility loci include AUTS3 (608049), which maps to chromosome 13q14; AUTS4 (608636), which maps to chromosome 15q11; AUTS6 (609378), which maps to chromosome 17q11; AUTS7 (610676), which maps to chromosome 17q21; AUTS8 (607373), which maps to chromosome 3q25-q27; AUTS9 (611015), which maps to chromosome 7q31; AUTS10 (611016), which maps to chromosome 7q36; AUTS11 (610836), which maps to chromosome 1q41; AUTS12 (610838), which maps to chromosome 21p13-q11; AUTS13 (610908), which maps to chromosome 12q14; AUTS14A (611913), which has been found in patients with a deletion of a region of 16p11.2; AUTS14B (614671), which has been found in patients with a duplication of a region of 16p11.2; AUTS15 (612100), associated with mutation in the CNTNAP2 gene (604569) on chromosome 7q35-q36; AUTS16 (613410), associated with mutation in the SLC9A9 gene (608396) on chromosome 3q24; AUTS17 (613436), associated with mutation in the SHANK2 gene (603290) on chromosome 11q13; AUTS18 (615032), associated with mutation in the CHD8 gene (610528) on chromosome 14q11; AUTS19 (615091), associated with mutation in the EIF4E gene (133440) on chromosome 4q23; and AUTS20 (618830), associated with mutation in the NLGN1 gene (600568) on chromosome 3q26. (NOTE: the symbol 'AUTS2' has been used to refer to a gene on chromosome 7q11 (KIAA0442; 607270) and therefore is not used as a part of this autism locus series.) There are several X-linked forms of autism susceptibility: AUTSX1 (300425), associated with mutations in the NLGN3 gene (300336); AUTSX2 (300495), associated with mutations in NLGN4 (300427); AUTSX3 (300496), associated with mutations in MECP2 (300005); AUTSX4 (300830), associated with variation in the region on chromosome Xp22.11 containing the PTCHD1 gene (300828); AUTSX5 (300847), associated with mutations in the RPL10 gene (312173); and AUTSX6 (300872), associated with mutation in the TMLHE gene (300777). A locus on chromosome 2q (606053) associated with a phenotype including intellectual disability and speech deficits was formerly designated AUTS5. Folstein and Rosen-Sheidley (2001) reviewed the genetics of autism.
Seizure
MedGen UID:
20693
Concept ID:
C0036572
Sign or Symptom
A seizure is an intermittent abnormality of nervous system physiology characterized 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.
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.
Encephalocele
MedGen UID:
1646412
Concept ID:
C4551722
Congenital Abnormality
A neural tube defect characterized by sac-like protrusions of the brain and the membranes that cover it through openings in the skull.
Micrognathia
MedGen UID:
44428
Concept ID:
C0025990
Congenital Abnormality
Developmental hypoplasia of the mandible.
Bronchial wall thickening
MedGen UID:
1826978
Concept ID:
C1868833
Disease or Syndrome
Radiological appearance of increased density around the walls of a bronchus or large bronchiole. This feature is thought to be related to edema involving the bronchial wall as well as the peribronchial interstitial space. If the cross section of a bronchus is captured in a radiograph or computed tomography image, it is said to have the appearance of a donut because of the central lucency representing the airway of the bronchus surrounded by a circular region of increased density.
Recurrent respiratory infections
MedGen UID:
812812
Concept ID:
C3806482
Finding
An increased susceptibility to respiratory infections as manifested by a history of recurrent respiratory infections.
Abnormal pulmonary interstitial morphology
MedGen UID:
1788738
Concept ID:
C5441745
Anatomical Abnormality
Abnormality of the lung parenchyma extending to the pulmonary interstitium and leading to diffuse pulmonary fibrosis.
Enamel hypoplasia
MedGen UID:
3730
Concept ID:
C0011351
Disease or Syndrome
Developmental hypoplasia of the dental enamel.
Single umbilical artery
MedGen UID:
278026
Concept ID:
C1384670
Congenital Abnormality
Single umbilical artery (SUA) is the absence of one of the two umbilical arteries surrounding the fetal bladder and in the fetal umbilical cord.
Vitreous floaters
MedGen UID:
5217
Concept ID:
C0016242
Finding
Deposits of various size, shape, consistency, refractive index, and motility within the eye's vitreous humor, which is normally transparent.
Retinal detachment
MedGen UID:
19759
Concept ID:
C0035305
Disease or Syndrome
Primary or spontaneous detachment of the retina occurs due to underlying ocular disease and often involves the vitreous as well as the retina. The precipitating event is formation of a retinal tear or hole, which permits fluid to accumulate under the sensory layers of the retina and creates an intraretinal cleavage that destroys the neurosensory process of visual reception. Vitreoretinal degeneration and tear formation are painless phenomena, and in most cases, significant vitreoretinal pathology is found only after detachment of the retina starts to cause loss of vision or visual field. Without surgical intervention, retinal detachment will almost inevitably lead to total blindness (summary by McNiel and McPherson, 1971).
High myopia
MedGen UID:
78759
Concept ID:
C0271183
Disease or Syndrome
A severe form of myopia with greater than -6.00 diopters.
Vitreoretinopathy
MedGen UID:
87480
Concept ID:
C0344290
Disease or Syndrome
Ocular abnormality characterized by premature degeneration of the vitreous and the retina that may be associated with increased risk of retinal detachment.
Anterior cortical cataract
MedGen UID:
347415
Concept ID:
C1857308
Finding
A cataract that affects the anterior part of the cortex of the lens.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  

Recent clinical studies

Etiology

Dumitrescu AV, Pfeifer WL, Drack AV
J AAPOS 2021 Aug;25(4):220.e1-220.e8. Epub 2021 Jul 17 doi: 10.1016/j.jaapos.2021.03.015. PMID: 34280564
Antonarakis SE, Holoubek A, Rapti M, Rademaker J, Meylan J, Iwaszkiewicz J, Zoete V, Wilson C, Taylor J, Ansar M, Borel C, Menzel O, Kuželová K, Santoni FA
Hum Mol Genet 2021 Dec 17;31(1):1-9. doi: 10.1093/hmg/ddab026. PMID: 33693784
Wawrzynski J, Than J, Gillam M, Foster PJ
J Glaucoma 2021 May 1;30(5):e265-e268. doi: 10.1097/IJG.0000000000001781. PMID: 33449584
AlBakri A, Ghazi NG, Khan AO
Ophthalmic Genet 2017 Mar-Apr;38(2):138-142. Epub 2016 Apr 18 doi: 10.3109/13816810.2016.1164197. PMID: 27088344
Cohen MM Jr, Lemire RJ
Teratology 1982 Apr;25(2):161-72. doi: 10.1002/tera.1420250206. PMID: 7101196

Diagnosis

Patel CK, Broadgate S, Shalaby A, Yu J, Nemeth AH, Downes SM, Halford S
Ophthalmic Genet 2022 Apr;43(2):201-209. Epub 2021 Nov 9 doi: 10.1080/13816810.2021.1998554. PMID: 34751625
Dumitrescu AV, Pfeifer WL, Drack AV
J AAPOS 2021 Aug;25(4):220.e1-220.e8. Epub 2021 Jul 17 doi: 10.1016/j.jaapos.2021.03.015. PMID: 34280564
Antonarakis SE, Holoubek A, Rapti M, Rademaker J, Meylan J, Iwaszkiewicz J, Zoete V, Wilson C, Taylor J, Ansar M, Borel C, Menzel O, Kuželová K, Santoni FA
Hum Mol Genet 2021 Dec 17;31(1):1-9. doi: 10.1093/hmg/ddab026. PMID: 33693784
AlBakri A, Ghazi NG, Khan AO
Ophthalmic Genet 2017 Mar-Apr;38(2):138-142. Epub 2016 Apr 18 doi: 10.3109/13816810.2016.1164197. PMID: 27088344
Hull S, Arno G, Ku CA, Ge Z, Waseem N, Chandra A, Webster AR, Robson AG, Michaelides M, Weleber RG, Davagnanam I, Chen R, Holder GE, Pennesi ME, Moore AT
JAMA Ophthalmol 2016 Jul 1;134(7):753-62. doi: 10.1001/jamaophthalmol.2016.1073. PMID: 27259167

Therapy

Alsulaiman SM, Al-Abdullah AA, Alakeely A, Aldhibi H, Engelbrecht L, Ghazi NG, Mura M
Ophthalmol Retina 2020 May;4(5):498-503. Epub 2019 Dec 12 doi: 10.1016/j.oret.2019.12.004. PMID: 32111543
Al-Beshri AS, Kozak I, Craven ER
Middle East Afr J Ophthalmol 2018 Jul-Dec;25(3-4):161-162. doi: 10.4103/meajo.MEAJO_263_17. PMID: 30765955Free PMC Article

Prognosis

Alzaben KA, Mousa A, Al-Abdi L, Alkuraya FS, Alsulaiman SM
Ophthalmol Retina 2024 Sep;8(9):898-904. Epub 2024 Mar 30 doi: 10.1016/j.oret.2024.03.020. PMID: 38556002
Antonarakis SE, Holoubek A, Rapti M, Rademaker J, Meylan J, Iwaszkiewicz J, Zoete V, Wilson C, Taylor J, Ansar M, Borel C, Menzel O, Kuželová K, Santoni FA
Hum Mol Genet 2021 Dec 17;31(1):1-9. doi: 10.1093/hmg/ddab026. PMID: 33693784
Balikova I, Sanak NS, Fanny D, Smits G, Soblet J, de Baere E, Cordonnier M
Ophthalmic Genet 2020 Feb;41(1):83-87. Epub 2020 Mar 17 doi: 10.1080/13816810.2020.1737948. PMID: 32178553
Khan AO, Ghazi NG
Ophthalmic Genet 2018 Jun;39(3):321-324. Epub 2018 Feb 1 doi: 10.1080/13816810.2018.1430245. PMID: 29388841
Kague E, Bessling SL, Lee J, Hu G, Passos-Bueno MR, Fisher S
Dev Biol 2010 Jan 15;337(2):496-505. Epub 2009 Nov 3 doi: 10.1016/j.ydbio.2009.10.028. PMID: 19895802

Clinical prediction guides

Vasilyeva T, Kadyshev V, Khalanskaya O, Kuznetsova S, Ionova S, Marakhonov A, Zinchenko R
Genes (Basel) 2024 Oct 1;15(10) doi: 10.3390/genes15101295. PMID: 39457419Free PMC Article
Antonarakis SE, Holoubek A, Rapti M, Rademaker J, Meylan J, Iwaszkiewicz J, Zoete V, Wilson C, Taylor J, Ansar M, Borel C, Menzel O, Kuželová K, Santoni FA
Hum Mol Genet 2021 Dec 17;31(1):1-9. doi: 10.1093/hmg/ddab026. PMID: 33693784
AlBakri A, Ghazi NG, Khan AO
Ophthalmic Genet 2017 Mar-Apr;38(2):138-142. Epub 2016 Apr 18 doi: 10.3109/13816810.2016.1164197. PMID: 27088344
Kague E, Bessling SL, Lee J, Hu G, Passos-Bueno MR, Fisher S
Dev Biol 2010 Jan 15;337(2):496-505. Epub 2009 Nov 3 doi: 10.1016/j.ydbio.2009.10.028. PMID: 19895802
Khaliq S, Abid A, White DR, Johnson CA, Ismail M, Khan A, Ayub Q, Sultana S, Maher ER, Mehdi SQ
Am J Med Genet A 2007 Dec 1;143A(23):2768-74. doi: 10.1002/ajmg.a.31739. PMID: 17975799

Supplemental Content

Recent activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...