Paula et Bobby
Parents de Lillie
Qu'est-ce que Cockayne syndrome?
Cockayne syndrome is a rare genetic condition that is usually diagnosed within the first two years of life. This rare disease was first identified in 1936 and named after the doctor who identified it.
There are 3 types of the syndrome: Type A is the classic form of the disease, Type B is the most severe form of the disease, with Type C being the mildest form.
Quelles sont les causes des changements génétiques Cockayne syndrome?
? des cas sont causés par des mutations du gène ERCC6. Les ? restants sont le résultat de mutations du gène ERCC8. Il est hérité selon un schéma autosomique récessif.
L'hérédité autosomique récessive signifie qu'un individu affecté reçoit une copie d'un gène muté de chacun de ses parents, ce qui lui donne deux copies d'un gène muté. Les parents qui ne portent qu'une seule copie de la mutation génique ne présenteront généralement aucun symptôme, mais auront 25% de chances de transmettre les copies des mutations génétiques à chacun de leurs enfants.
Quels sont les principaux symptômes de Cockayne syndrome?
Symptoms vary in their severity according to the type of the syndrome diagnosed.
Common physical symptoms include a small head, and short stature.
Unique facial characteristics include a long face, small chin, sunken eyes and big ears.
Failure to thrive in infancy, followed by a failure to grow properly in later childhood is also a feature of the syndrome.
The condition is progressive and most symptoms worsen with time. Other health conditions associated with the syndrome include issues with walking, an unstable gait, problems with balance, and abnormal reflexes.
Epilepsy presents in some individuals with the condition, as does hearing loss, and sun sensitivity due to very thin skin.
Individuals may also have issues with their liver, kidneys and an inability to sweat.
Genital abnormalities may present in males, and individuals with the disorder are unable to reproduce.
Several intellectual disabilities, zero to very limited speech development and premature ageing are also features of the syndrome.
Possible clinical traits/features:
Hypoplastic pelvis, Hypoplasia of teeth, Hypoplastic iliac wing, Hypogonadism, Opacification of the corneal stroma, Hepatomegaly, Kyphosis, Hypertension, Hypermetropia, Gait disturbance, Arrhythmia, Increased cellular sensitivity to UV light, Ivory epiphyses of the phalanges of the hand, Mandibular prognathia, Loss of facial adipose tissue, Irregular menstruation, Micropenis, Muscle weakness, Tremor, Intrauterine growth retardation, Intellectual disability, Abnormality of skin pigmentation, Cataract, Carious teeth, Anhidrosis, Abnormality of visual evoked potentials, Abnormality of the pinna, Cerebral atrophy, Ataxia, Atypical scarring of skin, Basal ganglia calcification, Severe postnatal growth retardation, Retinal pigment epithelial mottling, Sparse hair, Strabismus, Microcephaly, Progeroid facial appearance, Dry hair, Thickened calvaria, Square pelvis bone, Thymic hormone decreased, Reduced subcutaneous adipose tissue, Splenomegaly, Normal pressure hydrocephalus, Nystagmus, Sensorineural hearing impairment
Comment quelqu'un se fait-il tester pour Cockayne syndrome?
Les premiers tests de Cockayne syndrome peut commencer par un dépistage par analyse faciale, en passant par le FDNA Telehealth plateforme de télégénétique, qui permet d'identifier les marqueurs clés de la syndrome et souligner la nécessité de tests supplémentaires. Une consultation avec un conseiller génétique puis un généticien suivra.
Sur la base de cette consultation clinique avec un généticien, les différentes options pour les tests génétiques seront partagées et le consentement sera recherché pour des tests supplémentaires.
Informations médicales sur Cockayne syndrome
The phenotypic spectrum of Cockayne syndrome includes photosensitivity, growth failure and progressive neurologic dysfunction. There are three distinct forms of the disease: severe early-onset, moderate and mild. Mutations in several genes belonging to the ERCC family, including ERCC6 and ERCC8, cause Cockayne syndrome.
In its classical form, this progressive neurological disorder is characterized in infancy by sun sensitivity, resulting in bullae and desquamation of the skin. The characteristic facial appearance does not develop until between the 2nd and 4th years. There is a loss of subcutaneous tissue around the eyes, giving the appearance of premature ageing. The head circumference at this stage is small, as is length, and sensorineural hearing loss is common. Both central and peripheral demyelination result in loss of skills and features of a neuropathy, although limb reflexes can be exaggerated, especially at the knee. A retinopathy occurs late and may be accompanied by optic atrophy. Pericapillary calcification in the cortex and in the basal ganglia is a common feature. Nance and Berry (1992) provide an excellent review.
Chromosome breakage is seen on exposure of cells to UV light. Unlike in xeroderma pigmentosum, excision repair after UV damage is normal, but there is a slow recovery of DNA and RNA synthesis. Any excision repair defects seem to be restricted to actively transcribed genes (Venema et al., 1990).
Lehmann et al., (1993) reviewed their findings in investigating RNA synthesis in 52 possible cases of Cockayne syndrome. Twenty-nine showed an abnormality. Of the 23 normal cases, four were felt to have features that were clinically completely consistent with Cockayne syndrome according to the criteria of Nance and Berry (1992). Of the cases with an abnormal RNA response, photosensitivity was present in almost all cases, and pigmentary retinopathy and dental caries were felt to be good discriminatory clinical features.
The severe early-onset form of the disease is probably the same as cerebro-oculo-facio-skeletal (COFS) syndrome. There is also a moderate group (see Natale, 2011) who are physically larger, can sit independently and can self-feed. Some cases have a milder phenotype, some without abnormalities of DNA repair. They have better speech and can walk.
There may also be a later-onset form with normal intelligence and relatively normal growth (Fujiwara et al., 1981; Kennedy et al., 1980; Felgenhauer and Ammann, 1976; Lanning and Simila 1970). Miyauchi et al., (1994) reported two adult siblings (aged 42 and 55) with features of the condition. Their IQs were in the mild to moderately delayed range. Both showed extreme UV sensitivity but had almost normal UV-induced unscheduled DNA synthesis.
In complement group B patients, Troelstra et al., (1992) reported mutations in the ERCC6 gene, which is involved in the preferential repair of the transcribed strand of DNA. Further mutations in the ERCC6 gene were reported by Mallery et al., (1998).
Itoh (1996) showed that two cases with features of DeSanctis-Cacchione syndrome belonged to complementation group B of Cockayne syndrome. Oh et al., (2006) again point to the phenotypic heterogeneity (some of their XP patients had features of Cockayne) of mutations in the XPB DNA helicase gene (ERCC3). Greenshaw et al., (1992) reported a Hispanic family where three siblings had features of De Sanctis-Cacchione syndrome (qv) but the response of the cells to UV light was more characteristic of Cockayne syndrome.
Colella et al., (1999) reported mutations in the CSB gene in three patients without photosensitivity. Colella et al., (2000) also reported two patients with features of DeSanctis-Cacchione syndrome who had an identical mutation in the CSB gene as a patient with Cockayne syndrome reported by Mallery et al., (1998).
Henning et al., (1995) found mutations in a gene which they called CSA (also called CKN1) in complement group A patients.
Vermeulen et al., (1993) reported further studies on the children first described by Jaeken et al., (1989). They were found to have a biochemical defect typical of xeroderma pigmentosum, complementation group G, indicating that some mutations in the seven genes known to be involved in xeroderma pigmentosum can sometimes give rise to the picture of Cockayne syndrome. Hamel et al., (1996) and Moriwaki et al., (1996) reported further cases with overlapping features with xeroderma pigmentosum belonging to complementation group G. There were features of COFS syndrome.
O'Donovan and Wood (1993) showed that the XP-G complementing protein (XPGC) is likely to be the same as the mouse ERCC5 gene. Scherly et al., (1993) showed homology of this gene to the yeast RAD2 gene. In the human, the XPGC gene maps to 13q32-33. Nouspikel et al., (1997) demonstrated mutations in the gene in three patients with XPG/CF features.
Itoh et al., (1996, 1995, 1994) reported three cases with increased sensitivity to sunlight, including cutaneous photosensitivity, freckling, dryness, and telangiectasia, but without neurological abnormalities. These features were similar to xeroderma pigmentosum, however UV irradiation studies were more indicative of Cockayne syndrome. Cells from these patients do not appear to belong to any of the xeroderma pigmentosum or Cockayne syndrome complementation groups, however. The authors suggested the name ""UV-sensitive syndrome"" (UVs syndrome).
Other cases with features of xeroderma pigmentosum and Cockayne syndrome have been assigned to XP group D (Wood, 1991). Broughton et al., (1995) reported a case with mutations in the XPD gene, the product of which is one of the subunits of the transcription factor TFIIH.
XPD mutations are also seen in patients with trichothiodystrophy (qv). Broughton et al., (2001) reported a case with features overlapping xeroderma pigmentosum and tricothiodystrophy with a XPD mutation. Clinical photographs in the paper were suggestive of Cockayne syndrome, although there were no eye abnormalities. Coin et al., (1998) showed that the XPD gene product, which codes for a helicase, does not interact with p44, a subunit of TFIIH, if pathological mutations are present.
Czeizel et al., (1995) reported a case with normal intelligence, overlapping features of acrogeria but with skin photosensitivity. Reiss et al., (1996) reported a boy who died at the age of 6 years with some features of Cockayne syndrome. He had evidence of nephrotic syndrome, secondary to focal segmental glomerulosclerosis, adrenocortical failure and hypertension.
Cleaver et al., (1994) reported the experience of prenatal diagnosis in either amniotic fluid or CVS cells using assays of DNA repair after UV light irradiation. Kleijer et al., (2006) report on their experience of 15 years of prenatal diagnosis.
Mutations in ERCC1 and ERCC4 (XPF) have also been implicated (Kashiyama et al., 2013). In two cases, the clinical picture was that of classical Cockayne syndrome, but in one there were also features of Fanconi anemia and xeroderma pigmentosa.
Xie et al. (2017) described two male siblings with Cockayne syndrome due to compound heterozygous mutations in the ERCC8 gene (including a complex intragenic rearrangement). Clinical features were intellectual disability, short stature, microcephaly, growth delay, hypotonia, vision loss due to optic nerve atrophy and retinitis pigmentosa, hearing loss and photosensitivity. Dysmorphic features included broad nasal base, protruding ears, micrognathia, and poorly aligned teeth. Brain CT scans of the proband showed bilateral calcifications in globus pallidus, calcifications in the subcortex of the left frontal lobe, mild cerebral atrophy, and cerebellar vermis dysplasia.
* This information is courtesy of the L M D.
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Paula et Bobby
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