Ring chromosome 14 syndrome (r(14) syndrome) is a rare genetic disease with an unknown prevalence. It affects both males and females. Signs of the condition often appear in infancy. R(14) syndrome arises because of alterations to chromosome 14 during the early stages of development, resulting in the formation of an unstable ring chromosome. It is unclear whether this occurs before or after conception [1]. There are numerous ring chromosome syndromes recorded in the literature. A mosaic form of r(14) syndrome has been reported, which exhibits fewer clinical symptoms than the non-mosaic form [2].

One of the main features of r(14) syndrome is early onset epilepsy that is drug resistant and, in some cases, severe [3]. Epilepsy is a feature that has been reported in all affected individuals, and seizures may occur in any form, including generalized, partial, tonic-clonic, myoclonic, or focal [4]. Some patients proceed to status epilepticus. There is now evidence suggesting that the seizures experienced are focal seizures that may or may not progress to generalized convulsions [5]. Often, seizures are hypnagogic, hypnopompic, or occur during sleep. The frequency of the seizures changes as the disease progresses, and some patients may respond partially to drugs.

The R(14) syndrome is also typified by intellectual impairment and developmental delay, including speech delay [6]. Epilepsy that is more severe, or begins at an earlier age, is associated with a higher degree of intellectual impairment in affected individuals [7].

Typical physical manifestations of the disease include hypotonia, microcephaly, flat occiput, flat nasal bridge, anteverted nostrils, high arched palate, prominent epicanthal folds, and low set ears. Short neck or short stature may also be present. The skin and eyes (particularly the retina) may be affected by various pigmentation disorders, which may be observed as discoloration of skin, and retinopathy. There are numerous possible ocular abnormalities, such as strabismus, myopia and, less commonly, microphthalmia and colobomas [6] [8].

Other possible signs and symptoms of the condition include scoliosis, bone diseases and gastrointestinal complaints. Children with r(14) syndrome are at a higher risk of acquiring infections, particularly respiratory infections [9]; these vary in severity, and may require hospitalization.

• Recurrent Infection

  Some affected individuals have problems with their immune system that lead to recurrent infections, especially involving the respiratory system. [ghr.nlm.nih.gov]

  In a later stage, when the proband presented with recurrent infections, the deletion was shown to encompass the IgH gene using the LSI IGH/CCND1 combined probe, which is located at 14q32.33 at about 1 Mb from the telomere (data not shown). [nature.com]

• Recurrent Respiratory Infections

  Typically, children with this syndrome have distinct facial features, development delay, microcephaly, seizures, ocular abnormalities, and recurrent respiratory infections. [ncbi.nlm.nih.gov]

• Increased Susceptibility to Infections

  Other signs and symptoms may include a small head size (microcephaly), low muscle tone (hypotonia), scoliosis, and increased susceptibility to infections. [malacards.org]

• Painter

  Painter in 1922 was not certain whether the diploid of humans was 46 or 48, at first favouring 46, but revised his opinion from 46 to 48, considering the techniques of the time, these results were remarkable. [wikivisually.com]

• Inflammation

  The adaptive system is composed of more advanced lymphatic cells that are programmed to recognise self substances, the reaction to foreign substances is etymologically described as inflammation, meaning to set on fire. [wikivisually.com]

• Failure to Thrive

  They showed a phenotype consistent with the “ring syndrome” with failure to thrive, minor dysmporphic features and no major anomalies. [tp.amegroups.com]

• Small Hand

  In UPD(14) of maternal origin, clinical signs are less severe and characterized by hypotonia, feeding disorders in the first years of life, milder intellectual disability, short stature and small hands and feet. [ring14.org]

• Miosis

  الصفحة 358 - Ocular signs of cerebral involvement include the following: nystagmus, unilateral mydriasis, bilateral miosis with slow response to light, paralysis of accommodation, convergence, and 3rd, 4th, and 6th cranial nerve involvement. ‏ [books.google.com]

• Neonate-Onset

  Brunner, Boris Keren, Julien Thevenon, Laurence Faivre, Gary Thomas and Christel Thauvin-Robinet, A Recurrent De Novo PACS2 Heterozygous Missense Variant Causes Neonatal-Onset Developmental Epileptic Encephalopathy, Facial Dysmorphism, and Cerebellar [doi.org]

• Cognitive Impairment

  Epilepsy is the most common and serious neurological symptom in ring chromosome 14 syndrome, also characterised by mild dysmorphisms, acquired microcephaly, cognitive impairment, hypotonia and ocular abnormalities. [ncbi.nlm.nih.gov]

  This syndrome is also characterized by behavioral problems, mild cognitive impairment and learning disabilities. Tell me more Seizures usually are the first and major clinical symptom of this syndrome& and usually do not respond to medications. [epilepsy.com]

  A recognizable pattern of anomalies characterized by growth retardation, no major malformations except for a few minor anomalies, mild cognitive impairment has been observed in patients with an autosomal ring. [tp.amegroups.com]

• Cranial Nerve Involvement

  الصفحة 358 - Ocular signs of cerebral involvement include the following: nystagmus, unilateral mydriasis, bilateral miosis with slow response to light, paralysis of accommodation, convergence, and 3rd, 4th, and 6th cranial nerve involvement. ‏ [books.google.com]

• Aura

  Moeschler, Aura Janze, Jeanne Meck, Sarah T. South and Erica F. [doi.org]

Definitive diagnosis of ring chromosome 14 syndrome can only be made via genetic testing, such as karyotyping [10]. Although the identification of r(14) syndrome may be challenging, as none of its characteristic features are exclusive to the syndrome, clinicians may begin to suspect and test for it in cases of refractory epilepsy with the occurrence of neurological or psychological symptoms [11]. The recommended cytogenetic test is an array CGH (comparative genomic hybridization) analysis.

Routine labs such as a complete blood count, liver function test, urea and electrolytes, thyroid function tests, are recommended. Radiological examination may involve magnetic resonance imaging (MRI). Neurological, ophthalmologic and psychological examination are also important initial investigations. EEG (electroencephalography) is required, and may reveal slow wave activity with intermittent spiking [4] [5].

The material is in no way intended to replace professional medical care by a qualified specialist and should not be used as a basis for diagnosis or treatment. [orpha.net]

Treatment - Ring chromosome 14 syndrome Not supplied. Resources - Ring chromosome 14 syndrome Not supplied. [checkorphan.org]

This era was followed by improved environmental factors which operate to produce methods of medical treatment, introduction congenital cardiac malformations. [books.google.com]

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. [ghr.nlm.nih.gov]

Prognosis - Ring chromosome 14 syndrome Not supplied. Treatment - Ring chromosome 14 syndrome Not supplied. Resources - Ring chromosome 14 syndrome Not supplied. [checkorphan.org]

Because symptoms and severity can vary, the long-term outlook (prognosis) is difficult to predict and depends mainly on the health issues present and complications that may arise. [malacards.org]

Such elucidation can be useful to optimize treatment, further specify the prognosis or prevent recurrence of the disease or condition in the future, the initial task is to detect a medical indication to perform a diagnostic procedure. [wikivisually.com]

What is the prognosis? Diagnose. and explain pathway. Poor chance of survival Trisomy 13 - Patau syndrome Chromosome nondisjunction New female patient comes in. [quizlet.com]

Further detailed and accurate descriptions of mental development are urgently needed in order to extend the knowledge on their long term mental prognosis. [matsuishi-lab.org]

Their etiology is not precisely century with the first clinical recognition of known, so we have included chapters that dis symptoms and patterns for diagnosis of car cuss many aspects of congenital cardiac mal diovascular diseases. [books.google.com]

Using these techniques, we are exploring several genes that may contribute to the etiology of BA. [med.upenn.edu]

This article uses diagnostician as any of these person categories, a diagnostic procedure does not necessarily involve elucidation of the etiology of the diseases or conditions of interest, that is, what caused the disease or condition. [wikivisually.com]

The etiology of epilepsy in r20 syndrome has not been elucidated. [ng.neurology.org]

ORPHA:1440 Synonym(s): Ring 14 Ring chromosome 14 Prevalence: Inheritance: Not applicable or Unknown Age of onset: Childhood ICD-10: Q93.2 OMIM: 616606 UMLS: C2930916 MeSH: C535487 GARD: 6072 MedDRA: - Summary Epidemiology It has been described in about [orpha.net]

Pathophysiology The rarity of the r(14) syndrome, the size variability of the duplication/deletion, the occurrence of mosaicism, and other not yet fully elucidated mechanisms have so far prevented precise genotype-phenotype correlations [ 16 ]. [ojrd.biomedcentral.com]

Symptoms - Ring chromosome 14 syndrome Causes - Ring chromosome 14 syndrome Prevention - Ring chromosome 14 syndrome Not supplied. [checkorphan.org]

[…] chromosomes through karyotyping; while once born, one can do the following to ascertain a diagnosis of the condition: MRI EEG In terms of the management of ring chromosome 14 syndrome, anticonvulsive medication for seizures, as well as, proper therapy to help prevent [en.wikipedia.org]

Hospital for Sick Children Health A-Z Search a complete list of child health articles expand_more View All Drug A-Z Search a list of articles about medications expand_more View All Learning Hubs Browse a complete list of content groups Healthy Living & Prevention [aboutkidshealth.ca]

Is chronic lung disease in low birth weight infants preventable? A survey of eight centers. ‎ Página 84 - Tanner JM, Whitehouse RH, Marubini E, Resele LF. The adolescent growth spurt of boys and girls of the Harpenden growth study. ‎ [books.google.es]

Such elucidation can be useful to optimize treatment, further specify the prognosis or prevent recurrence of the disease or condition in the future, the initial task is to detect a medical indication to perform a diagnostic procedure. [wikivisually.com]

1. Rossi E, Riegel M, Messa J, et al. Duplications in addition to terminal deletions are present in a proportion of ring chromosomes: clues to the mechanisms of formation. J Med Genet. 2008;45(3):147-154.
2. Matalon R, Supple P, Wyandt H, Rosenthal IM. Transmission of ring 14 chromosome from mother to two sons. Am J Med Genet. 1990;36(4):381-385.
3. Incecik F, Hergüner MO, Mert G, Erdem S, Altunbaşak S. Ring chromosome 14 syndrome presenting with intractable epilepsy: a case report. Turk J Pediatr. 2013;55(5):549-551.
4. Imataka G, Noguchi M, Tsukada K, Takahashi T, Yamanouchi H, Arisaka O. Partial epilepsy and developmental delay in infant with ring chromosome 14. Genet Couns. 2013;24(1):81-83.
5. Giovannini S, Marangio L, Fusco C, et al. Epilepsy in ring 14 syndrome: a clinical and EEG study of 22 patients. Epilepsia. 2013;54(12):2204-2213.
6. Zollino M, Seminara L, Orteschi D, et al. The ring 14 syndrome: clinical and molecular definition. Am J Med Genet A. 2009;149A(6):1116-1124.
7. Zampini L, D’Odorico L, Zanchi P, Zollino M, Neri G. Linguistic and psychomotor development in children with chromosome 14 deletions. Clin Linguist Phon. 2012;26(11-12):962-973.
8. Salter CG, Baralle D, Collinson MN, Self JE. Expanding the ocular phenotype of 14q terminal deletions: A novel presentation of microphthalmia and coloboma in ring 14 syndrome with associated 14q32.31 deletion and review of the literature. Am J Med Genet A. 2016;170A(4):1017-1022.
9. Specchio N, Trivisano M, Serino D, et al. Epilepsy in ring 14 chromosome syndrome. Epilepsy Behav. 2012;25(4):585-592.
10. Miller DT, Adam MP, Aradhya S, et al. Consensus statement: chromosomal microarray is a first-tier clinical diagnostic test for individuals with developmental disabilities or congenital anomalies. Am J Hum Genet. 2010;86(5):749-764.
11. Redin C, Gérard B, Lauer J, et al. Efficient strategy for the molecular diagnosis of intellectual disability using targeted high-throughput sequencing. J Med Genet. 2014;51(11):724-736.