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Ring chromosome 14

MedGen UID:
419284
Concept ID:
C2930916
Disease or Syndrome
Synonym: Ring chromosome 14 syndrome
SNOMED CT: Ring chromosome 14 (702345009); Ring chromosome 14 syndrome (702345009); Ring 14 syndrome (702345009)
Modes of inheritance:
Unknown inheritance
MedGen UID:
989040
Concept ID:
CN307042
Finding
Source: Orphanet
Hereditary clinical entity whose mode of inheritance is unknown.
Not genetically inherited
MedGen UID:
988794
Concept ID:
CN307044
Finding
Source: Orphanet
clinical entity without genetic inheritance.
 
Monarch Initiative: MONDO:0014708
OMIM®: 616606
Orphanet: ORPHA1440

Definition

Ring chromosome 14 syndrome is a condition characterized by seizures and intellectual disability. Recurrent seizures (epilepsy) develop in infancy or early childhood. In many cases, the seizures are resistant to treatment with anti-epileptic drugs. Most people with ring chromosome 14 syndrome also have some degree of intellectual disability or learning problems. Development may be delayed, particularly the development of speech and of motor skills such as sitting, standing, and walking.

Additional features of ring chromosome 14 syndrome can include slow growth and short stature, a small head (microcephaly), puffy hands and/or feet caused by a buildup of fluid (lymphedema), and subtle differences in facial features. Some affected individuals have problems with their immune system that lead to recurrent infections, especially involving the respiratory system. Abnormalities of the retina, the specialized tissue at the back of the eye that detects light and color, have also been reported in some people with this condition. These changes typically do not affect vision. Major birth defects are rarely seen with ring chromosome 14 syndrome. [from MedlinePlus Genetics]

Clinical features

From HPO
Growth delay
MedGen UID:
99124
Concept ID:
C0456070
Pathologic Function
A deficiency or slowing down of growth pre- and postnatally.
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.
Status epilepticus
MedGen UID:
11586
Concept ID:
C0038220
Disease or Syndrome
Status epilepticus is a type of prolonged seizure resulting either from the failure of the mechanisms responsible for seizure termination or from the initiation of mechanisms which lead to abnormally prolonged seizures (after time point t1). It is a condition that can have long-term consequences (after time point t2), including neuronal death, neuronal injury, and alteration of neuronal networks, depending on the type and duration of seizures.
Generalized-onset seizure
MedGen UID:
115963
Concept ID:
C0234533
Disease or Syndrome
A generalized-onset seizure is a type of seizure originating at some point within, and rapidly engaging, bilaterally distributed networks. The networks may include cortical and subcortical structures but not necessarily the entire cortex.
Focal impaired awareness seizure
MedGen UID:
543022
Concept ID:
C0270834
Disease or Syndrome
Focal impaired awareness seizure (or focal seizure with impaired or lost awareness) is a type of focal-onset seizure characterized by some degree (which may be partial) of impairment of the person's awareness of themselves or their surroundings at any point during the seizure.
Delayed speech and language development
MedGen UID:
105318
Concept ID:
C0454644
Finding
A degree of language development that is significantly below the norm for a child of a specified age.
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.
Focal-onset seizure
MedGen UID:
199670
Concept ID:
C0751495
Disease or Syndrome
A focal-onset seizure is a type of seizure originating within networks limited to one hemisphere. They may be discretely localized or more widely distributed, and may originate in subcortical structures.
Poor speech
MedGen UID:
341172
Concept ID:
C1848207
Finding
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.
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.
Dolichocephaly
MedGen UID:
65142
Concept ID:
C0221358
Congenital Abnormality
An abnormality of skull shape characterized by a increased anterior-posterior diameter, i.e., an increased antero-posterior dimension of the skull. Cephalic index less than 76%. Alternatively, an apparently increased antero-posterior length of the head compared to width. Often due to premature closure of the sagittal suture.
Flat occiput
MedGen UID:
332439
Concept ID:
C1837402
Finding
Reduced convexity of the occiput (posterior part of skull).
Generalized hypotonia
MedGen UID:
346841
Concept ID:
C1858120
Finding
Generalized muscular hypotonia (abnormally low muscle tone).
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.
High palate
MedGen UID:
66814
Concept ID:
C0240635
Congenital Abnormality
Height of the palate more than 2 SD above the mean (objective) or palatal height at the level of the first permanent molar more than twice the height of the teeth (subjective).
Downslanted palpebral fissures
MedGen UID:
98391
Concept ID:
C0423110
Finding
The palpebral fissure inclination is more than two standard deviations below the mean.
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.
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).
Depressed nasal ridge
MedGen UID:
334631
Concept ID:
C1842876
Finding
Lack of prominence of the nose resulting from a posteriorly-placed nasal ridge.
Almond-shaped palpebral fissure
MedGen UID:
870336
Concept ID:
C4024780
Finding
A shape created by an acute downward arching of the upper eyelid and upward arching of the lower eyelid, toward the medial canthus, which gives the outline of the palpebral fissures the configuration of an almond. Thus, the maximum distance between the fissures is offset from, and medial to, the center point.
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).
Pigmentary retinopathy
MedGen UID:
1643295
Concept ID:
C4551715
Disease or Syndrome
An abnormality of the retina characterized by pigment deposition. It is typically associated with migration and proliferation of macrophages or retinal pigment epithelial cells into the retina; melanin from these cells causes the pigmentary changes. Pigmentary retinopathy is a common final pathway of many retinal conditions and is often associated with visual loss.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVRing chromosome 14
Follow this link to review classifications for Ring chromosome 14 in Orphanet.

Professional guidelines

PubMed

Rinaldi B, Vaisfeld A, Amarri S, Baldo C, Gobbi G, Magini P, Melli E, Neri G, Novara F, Pippucci T, Rizzi R, Soresina A, Zampini L, Zuffardi O, Crimi M
Orphanet J Rare Dis 2017 Apr 11;12(1):69. doi: 10.1186/s13023-017-0606-4. PMID: 28399932Free PMC Article

Recent clinical studies

Etiology

Ivanoff AE, Ivanoff CS
Folia Med (Plovdiv) 2023 Feb 28;65(1):20-29. doi: 10.3897/folmed.65.e71784. PMID: 36855970
Zampini L, Zanchi P, D'Odorico L
Clin Linguist Phon 2014 Nov;28(11):844-56. Epub 2014 Apr 29 doi: 10.3109/02699206.2014.911963. PMID: 24779649
Guilherme RS, de Freitas Ayres Meloni V, Sodré CP, Christofolini DM, Pellegrino R, de Mello CB, Conlin LK, Hutchinson AL, Spinner NB, Brunoni D, Kulikowski LD, Melaragno MI
Am J Med Genet A 2010 Nov;152A(11):2865-9. doi: 10.1002/ajmg.a.33689. PMID: 20979193
van Karnebeek CD, Quik S, Sluijter S, Hulsbeek MM, Hoovers JM, Hennekam RC
Am J Med Genet 2002 Jun 1;110(1):65-72. doi: 10.1002/ajmg.10207. PMID: 12116274
Atchaneeyasakul LO, Linck L, Weleber RG
Ophthalmic Genet 1998 Mar;19(1):39-48. doi: 10.1076/opge.19.1.39.2178. PMID: 9587928

Diagnosis

Ivanoff AE, Ivanoff CS
Folia Med (Plovdiv) 2023 Feb 28;65(1):20-29. doi: 10.3897/folmed.65.e71784. PMID: 36855970
Vasconcelos HM Jr, Vargas ME, Pennesi ME
Ophthalmic Genet 2019 Dec;40(6):541-544. Epub 2019 Nov 22 doi: 10.1080/13816810.2019.1688839. PMID: 31755799
Rinaldi B, Vaisfeld A, Amarri S, Baldo C, Gobbi G, Magini P, Melli E, Neri G, Novara F, Pippucci T, Rizzi R, Soresina A, Zampini L, Zuffardi O, Crimi M
Orphanet J Rare Dis 2017 Apr 11;12(1):69. doi: 10.1186/s13023-017-0606-4. PMID: 28399932Free PMC Article
Zampini L, Zanchi P, D'Odorico L
Clin Linguist Phon 2014 Nov;28(11):844-56. Epub 2014 Apr 29 doi: 10.3109/02699206.2014.911963. PMID: 24779649
Specchio N, Trivisano M, Serino D, Cappelletti S, Carotenuto A, Claps D, Marras CE, Fusco L, Elia M, Vigevano F
Epilepsy Behav 2012 Dec;25(4):585-92. Epub 2012 Nov 14 doi: 10.1016/j.yebeh.2012.09.032. PMID: 23159383

Therapy

Imataka G, Noguchi M, Tsukada K, Takahashi T, Yamanouchi H, Arisaka O
Genet Couns 2013;24(1):81-3. PMID: 23610869

Prognosis

Barbour K, Tian N, Yozawitz EG, Wolf S, McGoldrick PE, Sands TT, Nelson A, Basma N, Grinspan ZM
Epilepsia 2024 Aug;65(8):2341-2353. Epub 2024 May 25 doi: 10.1111/epi.18029. PMID: 38795333Free PMC Article
Vasconcelos HM Jr, Vargas ME, Pennesi ME
Ophthalmic Genet 2019 Dec;40(6):541-544. Epub 2019 Nov 22 doi: 10.1080/13816810.2019.1688839. PMID: 31755799
Zampini L, Zanchi P, D'Odorico L
Clin Linguist Phon 2014 Nov;28(11):844-56. Epub 2014 Apr 29 doi: 10.3109/02699206.2014.911963. PMID: 24779649
Guilherme RS, de Freitas Ayres Meloni V, Sodré CP, Christofolini DM, Pellegrino R, de Mello CB, Conlin LK, Hutchinson AL, Spinner NB, Brunoni D, Kulikowski LD, Melaragno MI
Am J Med Genet A 2010 Nov;152A(11):2865-9. doi: 10.1002/ajmg.a.33689. PMID: 20979193
van Karnebeek CD, Quik S, Sluijter S, Hulsbeek MM, Hoovers JM, Hennekam RC
Am J Med Genet 2002 Jun 1;110(1):65-72. doi: 10.1002/ajmg.10207. PMID: 12116274

Clinical prediction guides

Zampini L, Zanchi P, Rinaldi B, Novara F, Zuffardi O
Eur J Pediatr 2017 Apr;176(4):455-464. Epub 2017 Jan 25 doi: 10.1007/s00431-017-2859-2. PMID: 28124115
Schlade-Bartusiak K, Costa T, Summers AM, Nowaczyk MJ, Cox DW
Am J Med Genet A 2005 Oct 15;138A(3):218-24. doi: 10.1002/ajmg.a.30942. PMID: 16152642
Morimoto M, Usuku T, Tanaka M, Otabe O, Nishimura A, Ochi M, Takeuchi Y, Yoshioka H, Sugimoto T
Epilepsia 2003 Sep;44(9):1245-9. doi: 10.1046/j.1528-1157.2003.05403.x. PMID: 12919399
Jean M, Rival JM, Mensier A, Mirallié S, Lopes P, Barrière P
Fertil Steril 1997 Jan;67(1):164-5. doi: 10.1016/s0015-0282(97)81874-2. PMID: 8986702
Krawczun M, Melink G, Cervenka J
Am J Med Genet 1984 Feb;17(2):465-9. doi: 10.1002/ajmg.1320170209. PMID: 6702898

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