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Wolf-Hirschhorn syndrome (WHS)
O que é Wolf-Hirschhorn syndrome (WHS)?
Wolf-Hirschhorn síndromes é uma doença genética muito rara que se apresenta com características faciais muito distintas.
As características desta doença rara também incluem uma ampla gama de condições de saúde que afetam diferentes partes do corpo, incluindo crescimento físico retardado.
Como uma deleção cromossômica rara síndromes, a gravidade de sintomas pode variar de acordo com o tamanho da deleção cromossômica.
Síndromes Sinônimos:
Cromossomo 4 p16. 3 Exclusão Síndromes Pitt Síndromes Pitt-rogers-danks Síndromes; Prds Pitt-Rogers-Danks síndromes; PRDS Wittwer Síndromes
Quais mudanças genéticas causam Wolf-Hirschhorn syndrome (WHS)?
A síndromes ocorre devido à falta de um pedaço do braço curto do cromossomo 4.
Os indivíduos podem apresentar sintomas leves a mais graves do distúrbio, dependendo de quanto de um pedaço está faltando no cromossomo.
Na grande maioria dos casos, a síndrome não é hereditária. Em alguns casos, uma síndrome genética pode ser o resultado de uma mutação de novo e o primeiro caso em uma família. Neste caso, trata-se de uma nova mutação gênica que ocorre durante o processo reprodutivo.
Quais são os principais sintomas de Wolf-Hirschhorn syndrome (WHS)?
Os principais sintomas da síndromes são atraso no desenvolvimento e deficiência intelectual.
Problemas de alimentação, que se tornam graves e requerem um tubo de alimentação, também são comuns. Os indivíduos podem ser afetados por problemas gastrointestinais e nunca obter controle da bexiga e intestino.
Muitos indivíduos com a síndrome também são afetados por defeitos cardíacos e convulsões.
As características físicas da síndrome incluem olhos proeminentes e bem definidos, nariz largo ou pontudo, aparência de "capacete de guerreiro grego", glabela proeminente, testa alta, cabeça pequena, sobrancelhas arqueadas, lábio superior curto, orelhas inseridas baixas e malformadas (micrognatia) e baixo tônus muscular.
Como alguém faz o teste de Wolf-Hirschhorn syndrome (WHS)?
O teste inicial para a
Com base nesta consulta clínica com um geneticista, as diferentes opções para testes genéticos serão compartilhadas e o consentimento será solicitado para testes adicionais.
Informações médicas sobre Wolf-Hirschhorn síndromes
DISEASE OVERVIEW:
Wolf-Hirschhorn syndrome is a multiple congenital anomaly/developmental delay disorder due to deletions on the short arm of chromosome 4, typically including band 16 to the terminus. The cardinal features of this syndrome include: 1) prenatal and postnatal poor growth, 2) cognitive disability, 3) seizure disorder, 4) distinctive facial features (wide-spaced eyes, arched eyebrows, large forehead with high anterior hairline, prominent glabella with broad, prominent nasal bridge, and small face with short philtrum, small mouth with downturned corners, and micrognathia). The majority of cases are due to de novo deletions, with some de novo unbalanced translocations and other more unusual chromosome anomalies. Just over 10% of cases are due to inheritance of an unbalanced translocation from a parent with a balanced translocation.
CLINICAL DESCRIPTION (GENERAL):
Most patients present prenatally with in-utero growth retardation (IUGR) and are markedly small for gestational age at birth. Extremely poor growth in all body dimensions, including microcephaly, persists postnatally. Feeding problems are typical. Individuals have distinctive facial features (wide-spaced eyes, arched eyebrows, prominent glabella with broad, prominent nasal bridge, high anterior hairline, and small face, particularly including short philtrum and small mouth with downturned corners and micrognathia, leading to a disproportion between the forehead/eye region and the lower part of the face). The majority of individuals (95%) will go on to have a seizure disorder. Typical age of seizure onset is 6-12 months of age, but onset can be earlier or later. Seizures tend to improve in late childhood. All patients have some degree of developmental delay, and many will meet criteria for intellectual disability. Individuals may have other congenital anomalies, including skeletal anomalies, congenital heart defects, hearing loss, and abnormalities of the urinary tract.
CLINICAL DESCRIPTION (BODY SYSTEMS):
Constitutional: prenatal-onset persistent poor growth, premature aging
CNS: microcephaly, developmental delays, intellectual disability, seizures, hypotonia, congenital anomalies, particularly hypoplasia of the corpus callosum
Eye: exotropia/esotropia, foveal hypoplasia, chorioretinal coloboma, microcornea, ptosis, eyelid hypoplasia, glaucoma
Ear: underdeveloped, small, low-set, hearing loss, pits, tags
Face: wide-spaced eyes, highly arched eyebrows, prominent glabella, broad nasal root and bridge, high forehead, small face, short philtrum, prominence of the globes due to shallow orbits, micrognathia
Mouth: small mouth, cleft lip and palate, downturned corners of the mouth, short philtrum, hypodontia
Cardiovascular: septal defects
Abdomen: malrotation, absent gallbladder, accessory spleen
GU: hypospadias, cryptorchidism, absent uterus, chronic kidney disease progressing to end-stage renal disease
Musculoskeletal: hypotonia, low muscle mass, spinal anomalies, rib anomalies, developmental dysplasia of the hip, talipes equinovarus, polydactyly, split-hand malformation
Integument: mottled skin, scalp defects, premature greying of hair
Endocrine: precocious puberty, short stature
Allergy/Immunology/Heme: immune deficiency, hypogammaglobulinemia, neoplasia of the liver
SYNDROME CHARACTERISTICS:
PENETRANCE: 100%
PREVELANCE: 1:20,000-1:50,000 births, likely underdiagnosed
LIFE EXPECTANCY: Individuals typically survive into adulthood, although death in infancy or childhood can be seen
AGE OF ONSET: Prenatal
PRENATAL PESENTATION: In-utero growth retardation (IUGR), decreased fetal movements. Occasionally, anomalies such as cleft lip and palate or congenital heart disease may be identified. Experts may be able to recognize the facial phenotype on prenatal ultrasound
MOLECULAR GENETICS:
RECURRENT MUTATION(S): N/A
TYPE OF MUTATION(S): N/A
GENOTYPE/PHENOTYPE CORRELATION: This is an area of active investigation. In general, there is a trend towards a more severe phenotype in individuals with larger deletions and a milder phenotype in individuals with smaller deletions. Individuals with deletions proximal to 4p16.3 are more likely to have visceral anomalies. Phenotype is also impacted by the presence or absence of other chromosome anomalies, most commonly a partial duplication of another chromosome.
KEY CLINICAL FEATURES/PHENOTYPES:
The cardinal features of WHS are: 1) prenatal onset poor growth, 2) cognitive disability, 3) seizure disorder, and 4) typical distinctive facial features. Many other features may be seen to a variable degree.
Abnormality of the head or neck (100%): microcephaly and distinctive facial features
Abnormality of the skeletal system (50%): delayed bone age, fused ribs, scoliosis, kyphosis, abnormal vertebrae
Abnormality of the integument (50%): birthmarks, unusual appearance
Abnormality of the ear (50%): small ears, abnormally shaped ears, hearing loss
Abnormality of the limbs (75%): decreased muscle bulk, abnormal fingers and toes, clubfoot
Abnormality of the digestive system (50%): liver problems, including cholestasis malformations and dysfunction, malrotation, reflux
Abnormality of the nervous system (100%): developmental delays, (95%) seizures, (25%) structural brain anomalies
Abnormality of prenatal development or birth (>95): IUGR
Abnormality of the genitourinary system (25-50%): hypospadias, undescended testicles, female GU anomalies.
Abnormality of the musculature (75%): decreased muscle bulk
Neoplasm (unknown percentage): hepatic adenoma, hepatic carcinoma, hematologic malignancies
Growth abnormality (>95%): short stature, failure to thrive, microcephaly
Abnormality of the endocrine system (unknown percentage): precocious puberty, growth hormone deficiency
Abnormality of the cardiovascular system (25-50%): ASD, VSD, PDA, complex congenital heart disease much more rare
Abnormality of the eye (40%): small optic nerve, eye malformations, esotropia, ptosis; glaucoma is rare but can be serious.
Abnormality of the immune system (50%): antibody deficiency, occasionally T cell abnormalities as well
KEY PUBLICATIONS:
Recent excellent review in American Journal of Medical Genetics, Part C from 2015 by Dr. Agatino Battaglia, Dr. John C. Carey, and Dr. Sarah South. Large case series by Dr. Battaglia, Dr. Fillipi and Dr. Carey published in American Journal of Medical Genetics, Part C in 2008. Another excellent case series with a focus on genotype-phenotype correlation by Dr. Zollino and colleagues published in American Journal of Medical Genetics, part C in 2008. There are published growth charts for children less than 4 years of age: see Antonius and colleagues published in the European Journal of Pediatrics in 2008.
SURVEILLANCE:
A basic care recommendations flier is available on the 4p- Support group website at: http://4p-supportgroup.org/for-professionals/basic-care-recommendations/
At time of diagnosis:
72-hour video EEG
EKG
Echocardiogram
GI evaluation: feeding, reflux, dysmotility, low threshold to evaluate for malrotation
Ophthalmology evaluation
Audiology: brainstem auditory evoked response
Immunology testing: immunoglobulin levels, lymphocyte subsets, polysaccharide response
Complete blood count
Kidney function evaluation: BUN, creatinine, cystatin-c clearance, urinalysis, renal ultrasound
Developmental evaluation
Sleep study
Skeletal evaluation
Ongoing:
Regular neurology follow up, EEGs as needed
Annual CBC
Annual kidney function evaluation: BUN, creatinine, cystatin-C, urinalysis
Ongoing comprehensive developmental and rehabilitation support: communication, speech, feeding, PT, OT, preparation for adult transition
Yearly clinical evaluation for scoliosis
Consider (emerging evidence):
Liver ultrasound at diagnosis and yearly thereafter
Baseline and yearly kidney ultrasound
Growth hormone stimulation test
MANAGEMENT AND TREATMENT:
See surveillance guidelines
CLINICAL TRIALS:
N/A
PATIENT ORGANIZATIONS:
U.S.: 4p- Support Group: http://www.4p-supportgroup.org/
UK: Wolf Hirschhorn Syndrome Trust: http://whs4pminus.co.uk/
Italy: Assoziazione Italiana Sindrome di Wolf-Hirshhorn: http://www.aisiwh.it/
Spain: Asociacion Espanola del syndrome de Wolf-Hirschhorn: https://wolfhirschhorn.com/
DATE OF UPDATE:
Junho 11, 2018
* This information is courtesy of the L M D.
If you find a mistake or would like to contribute additional information, please email us at: [email protected]
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