Despite treatment with steroids and other immunosuppressive agents, the sisters died at ages 16 months and 5 years. The male patient was born at 28 weeks' gestation and exhibited repeated episodes of increased CRP levels, leukocytosis, and neutrophilia; he developed relapsing nodular panniculitis at 8 weeks of age.
A rare genetic autoinflammatory syndrome characterized by early-onset of repeated episodes of fever, nodular neutrophil-rich panniculitis, arthralgia, and lipodystrophy. Additional reported features include diarrhea, failure to thrive, lymphadenopathy, and vasculitis. Laboratory examination may reveal elevated serum C-reactive protein and leukocytosis with neutrophilia in the absence of infection.
Otulipenia is characterized by abnormal inflammation throughout the body. Inflammation is a normal immune system response to injury and foreign invaders (such as bacteria). However, the uncontrolled inflammation that occurs in otulipenia can damage many of the body's tissues and organs, including the gastrointestinal system, joints, and skin. Disorders such as otulipenia that result from abnormally increased inflammation are known as autoinflammatory diseases. Signs and symptoms of otulipenia usually begin within the first few weeks of life, with recurring episodes of fever; diarrhea; painful, swollen joints; and skin rashes.
Meunier et al. (2016) studied 42 members of the family from Martinique reported by Jean-Charles et al. (2013), and noted that all 14 clinically affected individuals were older than 30 years at presentation. The 28 asymptomatic family members, 12 of whom were older than 30 years, all had a normal fundus.
A rare, genetic retinal disease characterized by characteristic "dried-out soil" fundus pattern due to diffuse deep white lines in the macula, to the level of the retinal pigment epithelium, which is slightly elevated and rippled. Macular exudation may be associated, and Bruch's membrane may be affected too. Occasionally, peripheral nummular pigmentary changes may be observed, associated with blindness. The lesions enlarge with time, with a preferential macular extension and confluence. Complications may include polypoidal choroidal vasculopathy, choroidal neovascularization or atrophic fibrous macular scarring that can lead to reduced visual acuity over time.
Nevus of Ota is an oculodermal melanocytosis more commonly found in Asian and African populations, usually present at birth and characterized by a usually unilateral, bluish gray, patchy, speckled pigmentation (that may progressively enlarge and darken) affecting the skin of the face along the distribution of the ophthalmic and maxillary divisions of the trigeminal nerve (periorbital region, temple, forehead, malar area, nose). In 2/3 cases the ipsilateral sclera is affected. Nevus of Ota usually remains stable once adulthood is reached but an increased risk of glaucoma and uveal melanoma may be observed. Extracutaneous lesions may also occur in cornea, retina, tympanum, nasal mucosa, pharynx, palate. Nevus of Ota occurs as solitary conditions but seldom may occur together with the nevus of Ito or nevus spilus.
Summary Clinical characteristics. Individuals with X-linked dystonia-parkinsonism (XDP) have dystonia of varying severity and parkinsonism. XDP afflicts primarily Filipino men and, rarely, women. The mean age of onset in men is 39 years; the clinical course is highly variable with parkinsonism as the initial presenting sign, overshadowed by dystonia as the disease progresses. Features of parkinsonism include resting tremor, bradykinesia, rigidity, postural instability, and severe shuffling gait. The dystonia develops focally, most commonly in the jaw, neck, trunk, and eyes, and less commonly in the limbs, tongue, pharynx, and larynx, the most characteristic being jaw dystonia often progressing to neck dystonia. Individuals with pure parkinsonism have non-disabling symptoms that are only slowly progressive; those who develop a combination of parkinsonism and dystonia can develop multifocal or generalized symptoms within a few years and die prematurely from pneumonia or intercurrent infections.
X-linked dystonia-parkinsonism is a movement disorder that has been found only in people of Filipino descent. This condition affects men much more often than women. Parkinsonism is usually the first sign of X-linked dystonia-parkinsonism. Parkinsonism is a group of movement abnormalities including tremors, unusually slow movement (bradykinesia), rigidity, an inability to hold the body upright and balanced (postural instability), and a shuffling gait that can cause recurrent falls. Later in life, many affected individuals also develop a pattern of involuntary, sustained muscle contractions known as dystonia. The dystonia associated with X-linked dystonia-parkinsonism typically starts in one area, most often the eyes, jaw, or neck, and later spreads to other parts of the body.
Clinical Features Lee et al. (1976) identified an unusually high frequency of torsion dystonia in Panay, the sixth largest of the islands of the Philippines. Of 28 Filipino cases, 23 came from that island and 19 from the province of Capiz.
X-linked dystonia-parkinsonism (XDP) is a neurodegenerative movement disorder characterized by adult-onset parkinsonism that is frequently accompanied by focal dystonia, which becomes generalized over time, and that has a highly variable clinical course. Epidemiology Over 500 cases of XDP have been reported in the literature to date, all occurring in the Philippines (Panay Island). The estimated prevalence in the Philippines is 1/322,000 and in the Province of Capiz it is at its highest with a prevalence of 1/4,000 in the male population. Clinical description XDP affects mainly males, most female carriers are asymptomatic. The disease typically presents in adulthood (mean: 39 years) with either focal dystonia or, more commonly, parkinsonism.
She developed gait abnormalities 2 years later and was diagnosed with cerebellar atrophy at age 28. The disorder was slowly progressive, and she could still walk independently in middle age.
Spinocerebellar ataxia autosomal recessive 7 , also called SCAR7, is a slowly progressive hereditary form of spinocerebellar ataxia . Symptoms of SCAR7 can include difficulty walking and writing, speech difficulties (dysarthria), limb ataxia, and a decrease in the size of a region of the brain called the cerebellum (cerebellar atrophy). Of the few reported cases in the literature, some patients also had eye involvement that included nystagmus (in voluntary eye movements) and saccadic pursuit eye movements . Out of 5 affected siblings examined in a large Dutch family, 2 became wheelchair-dependent late in life. The severity of the symptoms varies from mild to severe. SCAR7 is caused by mutations in the TPP1 gene and is inherited in an autosomal recessive manner.
Brain imaging was normal in many and showed nonspecific white matter volume loss, atrophy of the corpus callosum, or cortical atrophy in a few patients. Three patients (27, 28, and 29) had a slightly milder phenotype, including 2 who had not developed seizures by age 4 years and 1 who had been seizure-free and was off medication at age 6.
Médecins Sans Frontières Luxembourg . 2017-09-28 . Retrieved 2017-10-06 . v t e Abortion in Africa Sovereign states Algeria Angola Benin Botswana Burkina Faso Burundi Cameroon Cape Verde (Cabo Verde) Central African Republic Chad Comoros Democratic Republic of the Congo Republic of the Congo Djibouti Egypt Equatorial Guinea Eritrea Eswatini (Swaziland) Ethiopia Gabon The Gambia Ghana Guinea Guinea-Bissau Ivory Coast (Côte d'Ivoire) Kenya Lesotho Liberia Libya Madagascar Malawi Mali Mauritania Mauritius Morocco Mozambique Namibia Niger Nigeria Rwanda São Tomé and Príncipe Senegal Seychelles Sierra Leone Somalia South Africa South Sudan Sudan Tanzania Togo Tunisia Uganda Zambia Zimbabwe States with limited recognition Sahrawi Arab Democratic Republic Somaliland Dependencies and other territories Canary Islands / Ceuta / Melilla (Spain) Madeira (Portugal) Mayotte / Réunion (France) Saint Helena / Ascension Island / Tristan da Cunha (United Kingdom) v t e Abortion Main topics Definitions History Methods Abortion debate Philosophical aspects Abortion law Movements Abortion-rights movements Anti-abortion movements Issues Abortion and mental health Beginning of human personhood Beginning of pregnancy controversy Abortion-breast cancer hypothesis Anti-abortion violence Abortion under communism Birth control Crisis pregnancy center Ethical aspects of abortion Eugenics Fetal rights Forced abortion Genetics and abortion Late-term abortion Legalized abortion and crime effect Libertarian perspectives on abortion Limit of viability Malthusianism Men's rights Minors and abortion Natalism One-child policy Paternal rights and abortion Prenatal development Reproductive rights Self-induced abortion Sex-selective abortion Sidewalk counseling Societal attitudes towards abortion Socialism Toxic abortion Unsafe abortion Women's rights By country Africa Algeria Angola Benin Botswana Burkina Faso Burundi Cameroon Cape Verde Central African Republic Chad Egypt Ghana Kenya Namibia Nigeria South Africa Uganda Zimbabwe Asia Afghanistan Armenia Azerbaijan Bahrain Bangladesh Bhutan Brunei Cambodia China Cyprus East Timor Georgia India Iran Israel Japan Kazakhstan South Korea Malaysia Nepal Northern Cyprus Philippines Qatar Saudi Arabia Singapore Turkey United Arab Emirates Vietnam Yemen Europe Albania Andorra Austria Belarus Belgium Bosnia and Herzegovina Bulgaria Croatia Czech Republic Denmark Estonia Finland France Germany Greece Hungary Iceland Ireland Italy Kazakhstan Latvia Liechtenstein Lithuania Luxembourg Malta Moldova Monaco Montenegro Netherlands North Macedonia Norway Poland Portugal Romania Russia San Marino Serbia Slovakia Slovenia Spain Sweden Switzerland Ukraine United Kingdom North America Belize Canada Costa Rica Cuba Dominican Republic El Salvador Guatemala Mexico Nicaragua Panama Trinidad and Tobago United States Oceania Australia Micronesia Fiji Kiribati Marshall Islands New Zealand Papua New Guinea Samoa Solomon Islands Tonga Tuvalu Vanuatu South America Argentina Bolivia Brazil Chile Colombia Ecuador Guyana Paraguay Peru Suriname Uruguay Venezuela Law Case law Constitutional law History of abortion law Laws by country Buffer zones Conscientious objection Fetal protection Heartbeat bills Informed consent Late-term restrictions Parental involvement Spousal consent Methods Vacuum aspiration Dilation and evacuation Dilation and curettage Intact D&X Hysterotomy Instillation Menstrual extraction Abortifacient drugs Methotrexate Mifepristone Misoprostol Oxytocin Self-induced abortion Unsafe abortion Religion Buddhism Christianity Catholicism Hinduism Islam Judaism Scientology Category This abortion -related article is a stub .
Hanna et al. (1995) reported a family with a variety of clinical features including congenital myopathy, mental retardation, cerebellar ataxia, and diabetes mellitus. Both the proband, a 28-year-old man, and his sister had congenital myopathy and mental retardation, and subsequently developed cerebellar ataxia.
A rare, genetic, mitochondrial DNA-related mitochondrial myopathy disorder characterized by slowly progressive muscular weakness (proximal greater than distal), predominantly involving the facial muscles and scapular girdle, associated with insulin-dependent diabetes mellitus. Neurological involvement and congenital myopathy may be variably observed.
In a metaanalysis of genomewide association studies conducted using 1,335 individuals with lone atrial fibrillation and 12,844 unaffected individuals, Ellinor et al. (2010) confirmed association on chromosome 4q25; the most significant SNP was rs6843082 (odds ratio, 2.03; p = 2.5 x 10(-28)). Molecular Genetics Ye et al. (2016) identified a functional SNP, rs2595104, within the ATFB5 locus identified by Gudbjartsson et al. (2007) on chromosome 4q25.
A number sign (#) is used with this entry because of evidence that familial atrial fibrillation-12 (ATFB12) is caused by heterozygous mutation in the ABCC9 gene (601439) on chromosome 12p12. Description Atrial fibrillation is the most common sustained cardiac rhythm disturbance, affecting more than 2 million Americans, with an overall prevalence of 0.89%. The prevalence increases rapidly with age, to 2.3% between the ages of 40 and 60 years, and to 5.9% over the age of 65. The most dreaded complication is thromboembolic stroke (Brugada et al., 1997). For a discussion of genetic heterogeneity of familial atrial fibrillation, see ATFB1 (608583).
A number sign (#) is used with this entry because of evidence that familial atrial fibrillation-7 (ATFB7) is caused by heterozygous mutation in the KCNA5 gene (176267) on chromosome 12p13. Description Atrial fibrillation (AF) is the most common sustained cardiac rhythm disturbance, affecting more than 2 million Americans, with an overall prevalence of 0.89%. The prevalence increases rapidly with age, to 2.3% between the ages of 40 and 60 years, and to 5.9% over the age of 65. The most dreaded complication is thromboembolic stroke (Brugada et al., 1997). For a discussion of genetic heterogeneity of atrial fibrillation, see 608583.
A number sign (#) is used with this entry because of evidence that autosomal dominant atrial fibrillation-3 (ATFB3) is caused by heterozygous mutation in the KCNQ1 gene (607542) on chromosome 11. Description Atrial fibrillation (AF) is the most common sustained cardiac rhythm disturbance, affecting more than 2 million Americans, with an overall prevalence of 0.89%. The prevalence increases rapidly with age, to 2.3% between the ages of 40 and 60 years, and to 5.9% over the age of 65. The most dreaded complication is thromboembolic stroke (Brugada et al., 1997). For a discussion of genetic heterogeneity of atrial fibrillation, see 608583.
A number sign (#) is used with this entry because of evidence that familial atrial fibrillation-13 (ATFB13) is caused by heterozygous mutation in the SCN1B gene (600235) on chromosome 19q13. Description Atrial fibrillation is the most common sustained cardiac rhythm disturbance, affecting more than 2 million Americans, with an overall prevalence of 0.89%. The prevalence increases rapidly with age, to 2.3% between the ages of 40 and 60 years, and to 5.9% over the age of 65. The most dreaded complication is thromboembolic stroke (Brugada et al., 1997). For a discussion of genetic heterogeneity of familial atrial fibrillation, see ATFB1 (608583).
Description Atrial fibrillation is the most common sustained cardiac rhythm disturbance, affecting more than 2 million Americans, with an overall prevalence of 0.89%. The prevalence increases rapidly with age, to 2.3% between the ages of 40 and 60 years, and to 5.9% over the age of 65. The most dreaded complication is thromboembolic stroke (Brugada et al., 1997). For a discussion of genetic heterogeneity of atrial fibrillation, see 608583. Mapping Gudbjartsson et al. (2009) expanded the genomewide association study on atrial fibrillation in Iceland, which had identified risk variants on 4q25 (see 611494), and tested the most significant associations in samples from Iceland, Norway, and the United States.
Familial atrial fibrillation is an inherited abnormality of the heart's normal rhythm. Atrial fibrillation is characterized by episodes of uncoordinated electrical activity (fibrillation) in the heart's upper chambers (the atria), which cause a fast and irregular heartbeat. If untreated, this abnormal heart rhythm (arrhythmia) can lead to dizziness, chest pain, a sensation of fluttering or pounding in the chest (palpitations), shortness of breath, or fainting (syncope). Atrial fibrillation also increases the risk of stroke and sudden death. Complications of atrial fibrillation can occur at any age, although some people with this heart condition never experience any health problems associated with the disorder.
A number sign (#) is used with this entry because of evidence that familial atrial fibrillation-15 (ATFB15) is caused by homozygous mutation in the NUP155 gene (606694) on chromosome 5p13. One such family has been reported. Description Atrial fibrillation (AF) is a supraventricular tachyarrhythmia characterized by uncoordinated atrial activation with consequent deterioration of atrial mechanical function. It is the most common sustained cardiac rhythm disturbance, and its prevalence increases as the population ages. An estimated 70,000 strokes each year are caused by atrial fibrillation (summary by Oberti et al., 2004). For a discussion of genetic heterogeneity of atrial fibrillation, see 608583.
Description Atrial fibrillation (AF) is the most common sustained cardiac rhythm disturbance, affecting more than 2 million Americans, with an overall prevalence of 0.89%. The prevalence increases rapidly with age, to 2.3% between the ages of 40 and 60 years, and to 5.9% over the age of 65. The most dreaded complication is thromboembolic stroke (Brugada et al., 1997). Genetic Heterogeneity of Familial Atrial Fibrillation ATFB1 shows linkage to chromosome 10q22-q24. ATFB2 (608988) maps to chromosome 6q. ATFB3 (607554) is caused by mutation in the KCNQ1 gene (607542) on chromosome 11.
A number sign (#) is used with this entry because of evidence that familial atrial fibrillation-11 (ATFB11) is caused by heterozygous mutation in the GJA5 gene (121013) on chromosome 1q21. Atrial fibrillation has also been associated with somatic mutation in the GJA5 gene. Description Atrial fibrillation is the most common sustained cardiac rhythm disturbance, affecting more than 2 million Americans, with an overall prevalence of 0.89%. The prevalence increases rapidly with age, to 2.3% between the ages of 40 and 60 years, and to 5.9% over the age of 65. The most dreaded complication is thromboembolic stroke (Brugada et al., 1997).
A number sign (#) is used with this entry because of evidence that familial atrial fibrillation-10 (ATFB10) is caused by heterozygous mutation in the SCN5A gene (600163) on chromosome 3p21. Description Atrial fibrillation is the most common sustained cardiac rhythm disturbance, affecting more than 2 million Americans, with an overall prevalence of 0.89%. The prevalence increases rapidly with age, to 2.3% between the ages of 40 and 60 years, and to 5.9% over the age of 65. The most dreaded complication is thromboembolic stroke (Brugada et al., 1997). For a discussion of genetic heterogeneity of atrial fibrillation, see 608583.
A number sign (#) is used with this entry because of evidence that familial atrial fibrillation-18 (ATFB18) is caused by mutation in the MYL4 gene (160770) on chromosome 17q21. One such family has been reported. For a general phenotypic description and a discussion of genetic heterogeneity of atrial fibrillation, see ATFB1 (608583). Clinical Features Orr et al. (2016) studied a 3-generation family with atrial fibrillation (AF), conduction disease, and reduced left atrial function. The proband was a 32-year-old woman who presented at age 26 years with palpitations, at which time electrocardiography (ECG) showed atrial fibrillation with a slow ventricular rate response. During periods of sinus rhythm, extremely low amplitude P-waves and prolonged atrioventricular (AV) conduction (first-degree AV block) were observed.
Familial atrial fibrillation is an inherited heart condition that disrupts the heart's rhythm. It is characterized by erratic electrical activity in the heart's upper chambers (the atria), causing an irregular response in the heart's lower chambers (the ventricles). This causes a fast and irregular heartbeat ( arrhythmia ). Signs and symptoms may include dizziness, chest pain, palpitations , shortness of breath, or fainting. Affected people also have an increased risk of stroke and sudden death. While complications may occur at any age, some affected people never have associated health problems.
A number sign (#) is used with this entry because of evidence that familial atrial fibrillation-9 (ATFB9) is caused by heterozygous mutation in the KCNJ2 gene (600681) on chromosome 17q24.3. Description Atrial fibrillation is the most common sustained cardiac rhythm disturbance, affecting more than 2 million Americans, with an overall prevalence of 0.89%. The prevalence increases rapidly with age, to 2.3% between the ages of 40 and 60 years, and to 5.9% over the age of 65. The most dreaded complication is thromboembolic stroke (Brugada et al., 1997). For a discussion of genetic heterogeneity of atrial fibrillation, see 608583.
A number sign (#) is used with this entry because of evidence that familial atrial fibrillation-6 (ATFB6) is caused by heterozygous mutation in the NPPA gene (108780) on chromosome 1p36. Description Atrial fibrillation (AF) is the most common sustained cardiac rhythm disturbance, affecting more than 2 million Americans, with an overall prevalence of 0.89%. The prevalence increases rapidly with age, to 2.3% between the ages of 40 and 60 years, and to 5.9% over the age of 65. The most dreaded complication is thromboembolic stroke (Brugada et al., 1997). For a discussion of genetic heterogeneity of atrial fibrillation, see 608583.
Description Atrial fibrillation is the most common sustained cardiac rhythm disturbance, affecting more than 2 million Americans, with an overall prevalence of 0.89%. The prevalence increases rapidly with age, to 2.3% between the ages of 40 and 60 years, and to 5.9% over the age of 65. The most dreaded complication is thromboembolic stroke (Brugada et al., 1997). For a discussion of genetic heterogeneity of atrial fibrillation, see 608583. Clinical Features Ellinor et al. (2003) reported a large kindred in which atrial fibrillation segregated as a simple autosomal dominant trait.
One patient, a 27-year-old French man, presented at age 28 months with proximal weakness of the upper limbs and proximal and distal weakness in the lower limbs.
A number sign (#) is used with this entry because congenital fiber-type disproportion (CFTD) can be caused by mutation in the ACTA1 (102610), SEPN1 (606210), or TPM3 (191030) genes. Mutations in the SEPN1 gene also cause rigid spine muscular dystrophy (RSMD1; 602771), which shows clinical overlap with CFTD. See also CFTDX (300580), which has been mapped to chromosome Xq13.1-q22.1. Description Congenital fiber-type disproportion (CFTD) myopathy is a genetically heterogeneous disorder in which there is relative hypotrophy of type 1 muscle fibers compared to type 2 fibers on skeletal muscle biopsy. However, these findings are not specific and can be found in many different myopathic and neuropathic conditions.
A rare genetic, congenital, non-dystrophic myopathy characterized by neonatal or infantile-onset hypotonia and mild to severe generalized muscle weakness. Epidemiology Prevalence is unknown. Clinical description Disease onset is typically at birth or within the first year of life. Limb weakness may be greatest in the limb girdle and proximal limb muscles, but weakness is never solely distal. Facial weakness is often present, resulting in a long face, high-arched palate, and tented upper lip. Ophthalmoplegia and bulbar weakness can be seen. Tendon reflexes are often decreased or absent.
For a general phenotypic description of congenital fiber-type disproportion, see CFTD (255310). Clinical Features Clarke et al. (2005) reported a 4-generation Australian family in which at least 7 males had marked congenital muscle weakness inherited in an X-linked pattern. All presented at birth with bilateral ptosis, facial weakness, poor suck, weak cry, generalized hypotonia, and respiratory insufficiency. Six infants died of respiratory failure between the 6 and 14 weeks of age; only 1 survived to age 5.5 years at the time of the report. The survivor had facial weakness and mild generalized limb weakness, but could walk fast, jump, and did not demonstrate Gowers sign.
Congenital fiber-type disproportion is a condition that primarily affects skeletal muscles, which are muscles used for movement. People with this condition typically experience muscle weakness (myopathy), particularly in the muscles of the shoulders, upper arms, hips, and thighs. Weakness can also affect the muscles of the face and muscles that control eye movement (ophthalmoplegia), sometimes causing droopy eyelids (ptosis ). Individuals with congenital fiber-type disproportion generally have a long face, a high arch in the roof of the mouth (high-arched palate ), and crowded teeth . Individuals with congenital fiber-type disproportion may have joint deformities (contractures) and an abnormally curved lower back (lordosis ) or a spine that curves to the side (scoliosis ).
Congenital fiber type disproportion is a type of congenital myopathy. Congenital myopathy refers to a group of muscle disorders that appear at birth or in infancy. Early signs and symptoms of congenital fiber type disproportion include floppiness, limb and facial weakness, and breathing problems. It is a genetic disease caused by mutations in the ACTA1 , SEPN1 , RYR1 or TPM3 genes. Depending on the gene and mutation involved, congenital fiber type disproportion can be passed through families in an autosomal recessive, autosomal dominant, or X-linked manner.
Histopathology of congental muscle fibre dysproportion showing predominance of type 1 fibres which appear to be atrophic (yellow arrows) and few type 2 fibres. ATPase staining (pH 4) of a muscle biopsy. Congenital fiber type disproportion ( CFTD ) is an inherited form of myopathy with small type 1 muscle fibers that may occur in a number of neurological disorders . [1] It has a relatively good outcome and follows a stable course. [2] While the exact genetics is unclear, there is an association with mutations in the genes TPM3 , ACTA1 and SEPN1 . [3] It is a rare condition. [4] History [ edit ] The condition was named by M. H. Brooke in 1973. [1] References [ edit ] ^ a b Clarke NF, North KN (October 2003). "Congenital fiber type dispropsortion—30 years on" . J. Neuropathol. Exp. Neurol . 62 (10): 977–89. doi : 10.1093/jnen/62.10.977 . PMID 14575234 . ^ Na SJ, Kim WK, Kim TS, Kang SW, Lee EY, Choi YC (August 2006).
"Acrocephalopolysyndactyly type II--Carpenter syndrome: clinical spectrum and an attempt at unification with Goodman and Summit syndromes". Am. J. Med. Genet . 28 (2): 311–24. doi : 10.1002/ajmg.1320280208 .
Congenital disorder of the skull and digits For the mountain, see Apert . Apert syndrome Other names Acrocephalo-syndactyly type 1 [1] Hand in Apert syndrome with syndactyly Specialty Medical genetics Apert syndrome is a form of acrocephalosyndactyly , a congenital disorder characterized by malformations of the skull, face, hands and feet. It is classified as a branchial arch syndrome, affecting the first branchial (or pharyngeal) arch , the precursor of the maxilla and mandible . Disturbances in the development of the branchial arches in fetal development create lasting and widespread effects. In 1906, Eugène Apert , a French physician, described nine people sharing similar attributes and characteristics. [2] Linguistically, in the term "acrocephalosyndactyly", acro is Greek for "peak", referring to the "peaked" head that is common in the syndrome; cephalo , also from Greek, is a combining form meaning "head"; syndactyly refers to webbing of fingers and toes.
A rare group of inherited congenital malformation disorders characterized by craniosynostosis and fusion or webbing of the fingers or toes, often with other associated manifestations. Epidemiology The exact prevalence and birth incidence of ACS syndromes are not known. Overall incidence of all forms of craniosynostosis is reported to be 1/2,000 to 1/2,500 live births, but only small minorities of these cases are syndromic and the ACS syndromes are only one of many that have craniosynostosis as a finding. Clinical description Acrocephalosyndactyly includes a number of syndromes with similar and sometimes overlapping clinical manifestations. All include single-suture or multisutural craniosynostosis with distinctive facial features, variable intellectual and developmental deficits, and variable forms of hand or foot abnormalities.
In addition, 21 patients had abnormal semicircular canals, 28 had jugular foraminal stenosis, 5 patients had Chiari I malformation, 5 had low-lying cerebellar tonsils, and 2 had posterior fossa arachnoid cysts.
Apert syndrome is characterized by fusion of the skull bones too early during development (craniosynostosis) and webbing of fingers and toes (syndactyly). Other signs and symptoms may include distinctive facial features, some of which may lead to dental and vision problems. People with Apert syndrome may also have mild to moderate intellectual disability. Apert syndrome is caused by a change (mutation) in the FGFR2 gene. It is inherited in an autosomal dominant manner, but many cases result from a new mutation in a person with no family history of the disorder (a de novo mutation). Treatment options depend on the symptoms in each person and may include surgery to separate the skull bones and relieve the pressure on the brain.
Bare lymphocyte syndrome type I (BLS I) is an inherited disorder of the immune system (primary immunodeficiency). Immunodeficiencies are conditions in which the immune system is not able to protect the body effectively from foreign invaders such as bacteria or viruses. Starting in childhood, most people with BLS I develop recurrent bacterial infections in the lungs and airways (respiratory tract ). These recurrent infections can lead to a condition called bronchiectasis, which damages the passages leading from the windpipe to the lungs (bronchi) and can cause breathing problems. Many people with BLS I also have open sores (ulcers) on their skin, usually on the face, arms, and legs.
A rare autosomal recessive primary immunodeficiency characterized by severe reduction in the cell surface expression of HLA class I molecules, typically resulting in childhood-onset of chronic bacterial infections of the respiratory tract evolving to widespread bronchiectasis and respiratory insufficiency. Sterile necrotizing granulomatous skin lesions mainly involving the extremities and the mid-face may be observed in some patients. Severe viral infections do not occur as part of the condition. Atypical variants without respiratory or cutaneous manifestations, as well as asymptomatic individuals have been reported.
A number sign (#) is used with this entry because bare lymphocyte syndrome type I can be caused by mutation in the TAP2 (170261), TAP1 (170260), or TAPBP (601962) gene. Clinical Features In the review by de la Salle et al. (1999), only 9 well-documented cases of HLA class I deficiency with normal expression of class II molecules were found. Contrary to type II (209920) and type III bare lymphocyte syndromes, which are characterized by the early onset of severe combined immunodeficiency, class I antigen deficiencies are not accompanied by particular pathologic manifestations during the first years of life, although chronic lung disease develops in late childhood. Also in contrast to type II or type III BLS, pathology of the gut (diarrhea) is not observed. Systemic infections have not been described in HLA class I-deficient patients.
Two subsequent pregnancies were terminated after studies showed periventricular white matter lesions and hyperechogenic foci in the basal ganglia between 28 and 34 weeks' gestation. Southern blot analysis of patient skeletal muscle and liver tissue showed multiple mitochondrial DNA deletions, which were not found in blood and fibroblasts, and there were similar findings in fetal autopsy tissues.
A number sign (#) is used with this entry because of evidence that Aicardi-Goutieres syndrome-7 (AGS7) is caused by heterozygous mutation in the IFIH1 gene (606951) on chromosome 2q24. Description Aicardi-Goutieres syndrome-7 is an autosomal dominant inflammatory disorder characterized by severe neurologic impairment. Most patients present in infancy with delayed psychomotor development, axial hypotonia, spasticity, and brain imaging changes, including basal ganglia calcification, cerebral atrophy, and deep white matter abnormalities. Laboratory evaluation shows increased alpha-interferon (IFNA1; 147660) activity with upregulation of interferon signaling and interferon-stimulated gene expression. Some patients may have normal early development followed by episodic neurologic regression (summary by Rice et al., 2014).
A number sign (#) is used with this entry because of evidence that Aicardi-Goutieres syndrome-1 (AGS1) is caused by homozygous, compound heterozygous, or heterozygous mutation in the TREX1 gene (606609) on chromosome 3p21. Description Aicardi-Goutieres syndrome is a genetically heterogeneous encephalopathy characterized in its most severe form by cerebral atrophy, leukodystrophy, intracranial calcifications, chronic cerebrospinal fluid (CSF) lymphocytosis, increased CSF alpha-interferon (IFNA1; 147660), and negative serologic investigations for common prenatal infections (Ali et al., 2006). AGS is phenotypically similar to in utero viral infection. Severe neurologic dysfunction becomes clinically apparent in infancy, and manifests as progressive microcephaly, spasticity, dystonic posturing, profound psychomotor retardation, and often death in early childhood. Outside the nervous system, thrombocytopenia, hepatosplenomegaly, and elevated hepatic transaminases along with intermittent fever may also erroneously suggest an infective process (Crow et al., 2006). In a review of AGS, Stephenson (2008) noted that an expanded phenotypic spectrum has been recognized and that most of the original criteria for diagnosis no longer apply: affected individuals may show later onset and may not have severe or progressive neurologic dysfunction, calcification of the basal ganglia, or CSF lymphocytosis.
A number sign (#) is used with this entry because of evidence that Aicardi-Goutieres syndrome-6 (AGS6) is caused by homozygous or compound heterozygous mutation in the ADAR gene (146920) on chromosome 1q21. Dyschromatosis symmetrica hereditaria (127400) is an allelic disorder. For a phenotypic description and a discussion of genetic heterogeneity of Aicardi-Goutieres syndrome, see AGS1 (225750). Clinical Features Rice et al. (2012) reported 10 families with 14 children, including 1 set of identical twins, with Aicardi-Goutieres syndrome. The families were of diverse ethnic backgrounds including Norwegian, Italian, Pakistani, Brazilian, Indian, British, Spanish, mixed Italian/Cuban, and European American.
A number sign (#) is used with this entry because of evidence that Aicardi-Goutieres syndrome-2 (AGS2) is caused by homozygous or compound heterozygous mutation in the gene encoding subunit B of ribonuclease H2 (RNASEH2B; 610326) on chromosome 13q14. For a general phenotypic description and a discussion of genetic heterogeneity of Aicardi-Goutieres syndrome, see AGS1 (225750). Clinical Features Ali et al. (2006) reported 17 children from 8 families with progressive neurodegeneration and encephalopathy beginning at birth or in infancy. Six of the families were consanguineous. All of the patients had evidence of intracranial calcification primarily affecting the basal ganglia; several had microcephaly. Laboratory studies showed lymphocytosis of the cerebrospinal fluid (CSF) and increased alpha-interferon in the CSF in most patients.
An inherited, subacute encephalopathy characterised by the association of basal ganglia calcification, leukodystrophy and cerebrospinal fluid (CSF) lymphocytosis. Epidemiology Just over 120 cases have been reported in the literature so far. Clinical description The majority of affected infants are born at full term with normal growth parameters. Onset occurs within the first few days or month of life with severe, subacute encephalopathy (feeding problems, irritability and psychomotor regression or delay) associated with epilepsy (53% of cases), chilblain skin lesions on the extremities (43% of cases) and episodes of aseptic febrile illness (40% of cases). Symptoms progress over several months (with the development of microcephaly and pyramidal signs) before the disease course stabilises.
Aicardi-Goutieres syndrome is an inherited disease that mainly affects the brain, immune system, and the skin. Loss of white matter in the brain (leukodystrophy) and abnormal deposits of calcium (calcification) in the brain leads to an early-onset severe brain dysfunction (encephalopathy) that usually results in severe intellectual and physical disability. Additional symptoms may include epilepsy, painful, itchy skin lesion ( chilblains ), vision problems, and joint and muscle stiffness (spasticity), involuntary muscle twisting and contractions (dystonia), and weak muscle tone (hypotonia) in the torso. Other signs and symptoms may include a very small head (microcephaly), presence of white blood cells and other sign of inflammation in the cerebrospinal fluid, which is the fluid that surrounds the brain and spinal cord (central nervous system). Symptoms usually progress over several months before the disease course stabilizes.
A number sign (#) is used with this entry because of evidence that Aicardi-Goutieres syndrome-3 (AGS3) is caused by homozygous mutation in the gene encoding subunit C of ribonuclease H2 (RNASEH2C; 610330) on chromosome 11q13. Description Aicardi-Goutieres syndrome is an autosomal recessive disorder characterized by onset of encephalopathy in the first year of life following normal early development. Affected infants typically show extreme irritability, intermittent unexplained fever, chilblains, progressive microcephaly, spasticity, dystonia, and profound psychomotor retardation. Laboratory studies show lymphocytosis and raised titers of alpha-interferon in the cerebrospinal fluid. Brain imaging may show white matter abnormalities, intracerebral calcifications, and cerebral atrophy.
A number sign (#) is used with this entry because Aicardi-Goutieres syndrome-4 (AGS4) is caused by homozygous or compound heterozygous mutation in the gene encoding subunit A of ribonuclease H2 (RNASEH2A; 606034) on chromosome 19p13. For a phenotypic description and a discussion of genetic heterogeneity of Aicardi-Goutieres syndrome, see AGS1 (225750). Clinical Features Sanchis et al. (2005) described 2 brothers, born of second-cousin parents of white Spanish ancestry, who had intrauterine growth retardation and clinical features suggestive of intrauterine infection but with negative bacteriologic and serologic investigations. At birth, the older brother was microcephalic with left peripheral facial paralysis and dysmorphic features including hooked nose with low-set anteriorly rotated ears. He had respiratory insufficiency requiring oxygen, hepatosplenomegaly, and spontaneous tremors with muscle tone shifting from hyper- to hypotonic.
Description Bilateral striopallidodentate calcinosis, also known as idiopathic basal ganglia calcification (IBGC), is characterized by the accumulation of calcium deposits in different brain regions and is associated with a neurodegenerative clinical phenotype. The changes seen in IBGC occur in the absence of calcium or parathyroid hormone (PTH; 168450) metabolic disorders, such as hypoparathyroidism (see 146200) or pseudohypoparathyroidism (PHP; see 103580). See also the adult-onset form (213600), which is sometimes erroneously referred to as 'Fahr disease.' Clinical Features Hallervorden (1950) observed 2 sibs with infantile onset of mental retardation, extrapyramidal signs, and diffuse, symmetric intracerebral calcium deposits in the basal ganglia, dentate nucleus, cortex, and subcortical white matter. The findings were associated with microcephaly and pathologic changes consistent with meningoencephalitis.
Summary Clinical characteristics. Most characteristically, Aicardi-Goutières syndrome (AGS) manifests as an early-onset encephalopathy that usually, but not always, results in severe intellectual and physical disability. A subgroup of infants with AGS present at birth with abnormal neurologic findings, hepatosplenomegaly, elevated liver enzymes, and thrombocytopenia, a picture highly suggestive of congenital infection. Otherwise, most affected infants present at variable times after the first few weeks of life, frequently after a period of apparently normal development. Typically, they demonstrate the subacute onset of a severe encephalopathy characterized by extreme irritability, intermittent sterile pyrexias, loss of skills, and slowing of head growth. Over time, as many as 40% develop chilblain skin lesions on the fingers, toes, and ears.
By size, where lymphadenopathy in adults is often defined as a short axis of one or more lymph nodes is greater than 10mm. [27] [28] However, there is regional variation as detailed in this table: Upper limit of lymph node sizes in adults Generally 10 mm [27] [28] Inguinal 10 [29] – 20 mm [30] Pelvis 10 mm for ovoid lymph nodes, 8 mm for rounded [29] Neck Generally (non-retropharyngeal) 10 mm [29] [31] Jugulodigastric lymph nodes 11mm [29] or 15 mm [31] Retropharyngeal 8 mm [31] Lateral retropharyngeal: 5 mm [29] Mediastinum Mediastinum , generally 10 mm [29] Superior mediastinum and high paratracheal 7mm [32] Low paratracheal and subcarinal 11 mm [32] Upper abdominal Retrocrural space 6 mm [33] Paracardiac 8 mm [33] Gastrohepatic ligament 8 mm [33] Upper paraaortic region 9 mm [33] Portacaval space 10 mm [33] Porta hepatis 7 mm [33] Lower paraaortic region 11 mm [33] Lymphadenopathy of the axillary lymph nodes can be defined as solid nodes measuring more than 15 mm without fatty hilum. [34] Axillary lymph nodes may be normal up to 30 mm if consisting largely of fat. [34] In children, a short axis of 8 mm can be used. [35] However, inguinal lymph nodes of up to 15 mm and cervical lymph nodes of up to 20 mm are generally normal in children up to age 8–12. [36] Lymphadenopathy of more than 1.5–2 cm increases the risk of cancer or granulomatous disease as the cause rather than only inflammation or infection . ... "North American poisonous bites and stings". Critical Care Clinics . 28 (4): 633–659. doi : 10.1016/j.ccc.2012.07.010 .
In November 2013 a coalition of Royal Colleges, trade unions and Equality Now produced a report, "Tackling FGM in the UK." [26] Britain's first specialist clinic for child victims of FGM opened in London in 2014. [27] Since April that year all NHS hospitals have recorded whether a patient has undergone FGM or has a family history of it, and all acute hospitals are obliged to report this data to the Department of Health on a monthly basis. [28] According to the first official figures published on the numbers of FGM cases seen by hospitals in England, over 1,700 women and girls who have undergone FGM were treated by the NHS between April and October 2014. [29] A 17-year-old student from Bristol, Fahma Mohamed, created with support from The Guardian an online petition on 6 February 2014 with Change.org , on the International Day of Zero Tolerance to Female Genital Mutilation . [30] The petition asked Michael Gove , then education secretary, to write to primary and secondary schools, encouraging them to be alert to FGM. ... Boulton, "Calls for female circumcision on the NHS sparks storm," The Observer , 14 February 1993. ^ Anna Davis (28 March 2014). "Ann John: I was branded a colonialist for fighting against 'barbaric' FGM" . ... The Guardian . ^ Topping, Alexandra (28 February 2014). "Fahma Mohamed: the shy campaigner who fought for FGM education" .
