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Coffin-Lowry syndrome(CLS)

MedGen UID:
75556
Concept ID:
C0265252
Congenital Abnormality; Disease or Syndrome
Synonyms: CLS; Coffin syndrome; COFFIN-LOWRY SYNDROME, MILD; Mental retardation with osteocartilaginous abnormalities
Modes of inheritance:
X-linked dominant inheritance
MedGen UID:
376232
Concept ID:
C1847879
Finding
Sources: HPO, OMIM, Orphanet
A mode of inheritance that is observed for dominant traits related to a gene encoded on the X chromosome. In the context of medical genetics, X-linked dominant disorders tend to manifest very severely in affected males. The severity of manifestation in females may depend on the degree of skewed X inactivation.
Sporadic
MedGen UID:
342827
Concept ID:
C1853237
Finding
Sources: HPO, OMIM
Cases of the disease in question occur without a previous family history, i.e., as isolated cases without being transmitted from a parent and without other siblings being affected.
X-linked dominant inheritance (HPO, OMIM, Orphanet)
Sporadic (HPO, OMIM)
SNOMED CT: CLS - Coffin-Lowry syndrome (15182000); Coffin-Lowry syndrome (15182000)
 
Gene (location): RPS6KA3 (Xp22.12)
OMIM®: 303600

Disease characteristics

Excerpted from the GeneReview: Coffin-Lowry Syndrome
Coffin-Lowry syndrome (CLS) is usually characterized by severe-to-profound intellectual disability in males; less severely impaired individuals have been reported. Intellect ranges from normal to profoundly impaired in heterozygous females. The facial appearance is characteristic in the affected, older male child or adult. The hands are short, soft, and fleshy, often with remarkably hyperextensible fingers that taper from wide (proximally) to narrow with small terminal phalanges and nails. Males are consistently below the third centile in height. Microcephaly is common. Cardiac abnormalities may be present and can contribute to premature death. Stimulus-induced drop attacks (SIDAs) in which unexpected tactile or auditory stimuli or excitement triggers a brief collapse but no loss of consciousness are present in approximately 20% of affected individuals. Typically SIDAs begin between mid-childhood and the teens. Progressive kyphoscoliosis is one of the most difficult aspects of long-term care. Life span may be reduced. [from GeneReviews]
Authors:
R Curtis Rogers  |  Fatima E Abidi   view full author information

Additional descriptions

From OMIM
Coffin-Lowry syndrome is a rare form of X-linked mental retardation characterized by skeletal malformations, growth retardation, hearing deficit, paroxysmal movement disorders, and cognitive impairment in affected males and some carrier females (Kesler et al., 2007). Hendrich and Bickmore (2001) reviewed human disorders which share in common defects of chromatin structure or modification, including the ATR-X spectrum of disorders (301040), ICF syndrome (242860), Rett syndrome (312750), Rubinstein-Taybi syndrome (180849), and Coffin-Lowry syndrome. Marques Pereira et al. (2010) provided a review of Coffin-Lowry syndrome. Mutation in the RPS6KA3 gene can also cause nonsyndromic X-linked mental retardation-19 (MRX19; 300844), a milder disorder without skeletal anomalies.  http://www.omim.org/entry/303600
From GHR
Coffin-Lowry syndrome is a condition that affects many parts of the body. The signs and symptoms are usually more severe in males than in females, although the features of this disorder range from very mild to severe in affected women.Males with Coffin-Lowry syndrome typically have severe to profound intellectual disability and delayed development. Affected women may be cognitively normal, or they may have intellectual disability ranging from mild to profound. Beginning in childhood or adolescence, some people with this condition experience brief episodes of collapse when excited or startled by a loud noise. These attacks are called stimulus-induced drop episodes (SIDEs).Most affected males and some affected females have distinctive facial features including a prominent forehead, widely spaced and downward-slanting eyes, a short nose with a wide tip, and a wide mouth with full lips. These features become more pronounced with age. Soft hands with short, tapered fingers are also characteristic of Coffin-Lowry syndrome. Additional features of this condition include short stature, an unusually small head (microcephaly), progressive abnormal curvature of the spine (kyphoscoliosis), and other skeletal abnormalities.  https://ghr.nlm.nih.gov/condition/coffin-lowry-syndrome

Clinical features

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.
Broad palm
MedGen UID:
75535
Concept ID:
C0264142
Disease or Syndrome
For children from birth to 4 years of age the palm width is more than 2 SD above the mean; for children from 4 to 16 years of age the palm width is above the 95th centile; or, the width of the palm appears disproportionately wide for the length.
Single transverse palmar crease
MedGen UID:
96108
Concept ID:
C0424731
Finding
The distal and proximal transverse palmar creases are merged into a single transverse palmar crease.
Tapered finger
MedGen UID:
98098
Concept ID:
C0426886
Finding
The gradual reduction in girth of the digit from proximal to distal.
Hyperextensibility of the finger joints
MedGen UID:
334982
Concept ID:
C1844577
Finding
The ability of the finger joints to move beyond their normal range of motion.
Underweight
MedGen UID:
11989
Concept ID:
C0041667
Finding
Short stature
MedGen UID:
87607
Concept ID:
C0349588
Finding
Height greater than two standard deviations below the mean of the appropriate reference population for the age and sex of the individual.
Inguinal hernia
MedGen UID:
6817
Concept ID:
C0019294
Finding
An abdominal hernia with an external bulge in the GROIN region. It can be classified by the location of herniation. Indirect inguinal hernias occur through the internal inguinal ring. Direct inguinal hernias occur through defects in the ABDOMINAL WALL (transversalis fascia) in Hesselbach's triangle. The former type is commonly seen in children and young adults; the latter in adults.
Rectal prolapse
MedGen UID:
11151
Concept ID:
C0034888
Disease or Syndrome
Protrusion of the rectal mucous membrane through the anus.
Sensorineural hearing loss
MedGen UID:
9164
Concept ID:
C0018784
Disease or Syndrome
Hearing loss resulting from damage to the COCHLEA and the sensorineural elements which lie internally beyond the oval and round windows. These elements include the AUDITORY NERVE and its connections in the BRAINSTEM.
Muscular hypotonia
MedGen UID:
10133
Concept ID:
C0026827
Finding
Muscular hypotonia is an abnormally low muscle tone (the amount of tension or resistance to movement in a muscle), often involving reduced muscle strength. Hypotonia is characterized by a diminished resistance to passive stretching.
Tapered finger
MedGen UID:
98098
Concept ID:
C0426886
Finding
The gradual reduction in girth of the digit from proximal to distal.
Narrow iliac wings
MedGen UID:
373150
Concept ID:
C1836688
Finding
Decreased width of the wing (or ala) of the ilium (which is the large expanded portion which bounds the greater pelvis laterally).
Hyperextensibility of the finger joints
MedGen UID:
334982
Concept ID:
C1844577
Finding
The ability of the finger joints to move beyond their normal range of motion.
Open mouth
MedGen UID:
116104
Concept ID:
C0240379
Spatial Concept
A facial appearance characterized by a permanently or nearly permanently opened mouth.
Microcephaly
MedGen UID:
473122
Concept ID:
C0424688
Finding
Occipito-frontal (head) circumference (OFC) less than -3 standard deviations compared to appropriate, age matched, normal standards (Ross JJ, Frias JL 1977, PMID:9683597). Alternatively, decreased size of the cranium.
Thickened calvaria
MedGen UID:
346823
Concept ID:
C1858452
Finding
The presence of an abnormally thick calvaria.
Everted lower lip vermilion
MedGen UID:
355663
Concept ID:
C1866234
Finding
An abnormal configuration of the lower lip such that it is turned outward i.e., everted, with the Inner aspect of the lower lip vermilion (normally opposing the teeth) being visible in a frontal view.
Delayed closure of the anterior fontanelle
MedGen UID:
825928
Concept ID:
C3840083
Finding
A delay in closure (ossification) of the anterior fontanelle, which generally undergoes closure around the 18th month of life.
Inguinal hernia
MedGen UID:
6817
Concept ID:
C0019294
Finding
An abdominal hernia with an external bulge in the GROIN region. It can be classified by the location of herniation. Indirect inguinal hernias occur through the internal inguinal ring. Direct inguinal hernias occur through defects in the ABDOMINAL WALL (transversalis fascia) in Hesselbach's triangle. The former type is commonly seen in children and young adults; the latter in adults.
Uterine prolapse
MedGen UID:
22591
Concept ID:
C0042140
Finding
The presence of prolapse of the uterus.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVCoffin-Lowry syndrome
Follow this link to review classifications for Coffin-Lowry syndrome in Orphanet.

Recent clinical studies

Etiology

Morino T, Ogata T, Horiuchi H, Yamaoka S, Fukuda M, Miura H
Medicine (Baltimore) 2016 Aug;95(31):e4468. doi: 10.1097/MD.0000000000004468. PMID: 27495083Free PMC Article
Igari K, Hozumi Y, Monma Y, Mayanagi H
Int J Paediatr Dent 2006 May;16(3):213-7. doi: 10.1111/j.1365-263X.2006.00698.x. PMID: 16643544
Stephenson JB, Hoffman MC, Russell AJ, Falconer J, Beach RC, Tolmie JL, McWilliam RC, Zuberi SM
Brain Dev 2005 Mar;27(2):108-13. doi: 10.1016/j.braindev.2003.11.010. PMID: 15668049
Nelson GB, Hahn JS
Pediatrics 2003 Mar;111(3):e197-202. PMID: 12612271
Simensen RJ, Abidi F, Collins JS, Schwartz CE, Stevenson RE
Clin Genet 2002 Apr;61(4):299-304. PMID: 12030896

Diagnosis

Morino T, Ogata T, Horiuchi H, Yamaoka S, Fukuda M, Miura H
Medicine (Baltimore) 2016 Aug;95(31):e4468. doi: 10.1097/MD.0000000000004468. PMID: 27495083Free PMC Article
Imataka G, Nakajima I, Goto K, Konno W, Hirabayashi H, Arisaka O
Eur Rev Med Pharmacol Sci 2016;20(3):498-501. PMID: 26914125
Loupe J, Sampath S, Lacassie Y
Eur J Med Genet 2014 Oct;57(10):562-6. Epub 2014 Aug 10 doi: 10.1016/j.ejmg.2014.08.002. PMID: 25118007
Rojnueangnit K, Jones JR, Basehore MJ, Robin NH
Am J Med Genet A 2014 Feb;164A(2):516-21. Epub 2013 Dec 5 doi: 10.1002/ajmg.a.36299. PMID: 24311527
Martinez HR, Niu MC, Sutton VR, Pignatelli R, Vatta M, Jefferies JL
Am J Med Genet A 2011 Dec;155A(12):3030-4. Epub 2011 Oct 18 doi: 10.1002/ajmg.a.33856. PMID: 22009732

Therapy

van Egmond ME, Elting JW, Kuiper A, Zutt R, Heineman KR, Brouwer OF, Sival DA, Willemsen MA, Tijssen MA, de Koning TJ
Eur J Paediatr Neurol 2015 Nov;19(6):726-9. Epub 2015 Jul 21 doi: 10.1016/j.ejpn.2015.07.003. PMID: 26232052
Jurkiewicz D, Jezela-Stanek A, Ciara E, Piekutowska-Abramczuk D, Kugaudo M, Gajdulewicz M, Chrzanowska K, Popowska E, Krajewska-Walasek M
Eur J Med Genet 2010 Sep-Oct;53(5):268-73. Epub 2010 Jul 15 doi: 10.1016/j.ejmg.2010.07.006. PMID: 20637903
Havaligi N, Matadeen-Ali C, Khurana DS, Marks H, Kothare SV
Pediatr Neurol 2007 Nov;37(5):373-4. doi: 10.1016/j.pediatrneurol.2007.06.025. PMID: 17950427
Fryssira H, Kountoupi S, Delaunoy JP, Thomaidis L
Genet Couns 2002;13(4):405-9. PMID: 12558110
Caraballo R, Tesi Rocha A, Medina C, Fejerman N
Epileptic Disord 2000 Sep;2(3):173-6. PMID: 11022143

Prognosis

Morino T, Ogata T, Horiuchi H, Yamaoka S, Fukuda M, Miura H
Medicine (Baltimore) 2016 Aug;95(31):e4468. doi: 10.1097/MD.0000000000004468. PMID: 27495083Free PMC Article
Yoshida T, Ohashi T, Furui M, Kageyama S, Kodani N, Kobayashi Y, Hirai Y, Sakakura R
Gen Thorac Cardiovasc Surg 2015 May;63(5):290-2. Epub 2013 Jul 20 doi: 10.1007/s11748-013-0291-8. PMID: 23873216
Kesler SR, Simensen RJ, Voeller K, Abidi F, Stevenson RE, Schwartz CE, Reiss AL
Neurogenetics 2007 Apr;8(2):143-7. Epub 2007 Feb 22 doi: 10.1007/s10048-007-0080-6. PMID: 17318637Free PMC Article
Igari K, Hozumi Y, Monma Y, Mayanagi H
Int J Paediatr Dent 2006 May;16(3):213-7. doi: 10.1111/j.1365-263X.2006.00698.x. PMID: 16643544
Coffin GS
Genet Med 2003 May-Jun;5(3):187-93. doi: 10.1097/01.GIM.0000067991.73943.4F. PMID: 12792428

Clinical prediction guides

Morino T, Ogata T, Horiuchi H, Yamaoka S, Fukuda M, Miura H
Medicine (Baltimore) 2016 Aug;95(31):e4468. doi: 10.1097/MD.0000000000004468. PMID: 27495083Free PMC Article
Mehmood T, Schneider A, Sibille J, Marques Pereira P, Pannetier S, Ammar MR, Dembele D, Thibault-Carpentier C, Rouach N, Hanauer A
Hum Genet 2011 Mar;129(3):255-69. Epub 2010 Nov 30 doi: 10.1007/s00439-010-0918-0. PMID: 21116650
Kesler SR, Simensen RJ, Voeller K, Abidi F, Stevenson RE, Schwartz CE, Reiss AL
Neurogenetics 2007 Apr;8(2):143-7. Epub 2007 Feb 22 doi: 10.1007/s10048-007-0080-6. PMID: 17318637Free PMC Article
Herrera-Soto JA, Santiago-Cornier A, Segal LS, Ramirez N, Tamai J
J Pediatr Orthop 2007 Jan-Feb;27(1):85-9. doi: 10.1097/01.bpo.0000187994.94515.9d. PMID: 17195803
Zeniou M, Gattoni R, Hanauer A, Stévenin J
Nucleic Acids Res 2004;32(3):1214-23. Epub 2004 Feb 18 doi: 10.1093/nar/gkh272. PMID: 14973203Free PMC Article

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