Familial steroid-resistant nephrotic syndrome with sensorineural deafness is a rare, genetic coenzyme Q10 deficiency characterized by sensorineural deafness and severe, progressive nephrotic syndrome not responding to steroid treatment.
Description Primary coenzyme Q10 deficiency-6 is an autosomal recessive disorder characterized by onset in infancy of severe progressive nephrotic syndrome resulting in end-stage renal failure and sensorineural deafness. ... For a general phenotypic description and a discussion of genetic heterogeneity of focal segmental glomerulosclerosis and nephrotic syndrome, see FSGS1 (603278) and NPHS1 (256300). Clinical Features Heeringa et al. (2011) reported 11 children from 5 families with autosomal recessive coenzyme Q10 deficiency manifest as nephrotic syndrome. Nine of the 11 patients had sensorineural deafness. ... Molecular Genetics By positional cloning, Heeringa et al. (2011) identified homozygous or compound heterozygous pathogenic mutations in the COQ6 gene (614647.0001-614647.0004) in 11 children from 5 families with autosomal recessive coenzyme Q deficiency manifest as nephrotic syndrome. Subsequent analysis of the COQ6 gene in 530 families with nephrotic syndrome identified 2 heterozygous truncating mutations in 2 unrelated patients (614647.0005 and 614647.0006, respectively); a second pathogenic mutation was not found in these 2 patients. INHERITANCE - Autosomal recessive HEAD & NECK Ears - Sensorineural deafness GENITOURINARY Kidneys - Nephrotic syndrome - Focal segmental glomerulosclerosis - Diffuse mesangial sclerosis (less common) - Proteinuria NEUROLOGIC Central Nervous System - Seizures (uncommon) LABORATORY ABNORMALITIES - Proteinuria MISCELLANEOUS - Onset in infancy - Rapidly progressive - Death in childhood may occur due to end-stage renal disease - Treatment with oral coenzyme Q may ameliorate symptoms MOLECULAR BASIS - Caused by mutation in the homolog of the S. cerevisiae COQ6 gene (COQ6, 614647.0001 ) ▲ Close
Spastic paraplegia-optic atrophy-neuropathy (SPOAN) syndrome is a rare, complex type of hereditary spastic paraplegia characterized by early-onset progressive spastic paraplegia presenting in infancy, associated with optic atrophy, fixation nystagmus, polyneuropathy occurring in late childhood/early adolescence leading to severe motor disability and progressive joint contractures and scoliosis. SPOAN syndrome is caused by mutations in the KLC2 gene (11q13.1), encoding kinesin light chain 2.
A number sign (#) is used with this entry because of evidence that spastic paraplegia, optic atrophy, and neuropathy (SPOAN) is caused by homozygous mutation in the KLC2 gene (611729) on chromosome 11q13.2. Description Spastic paraplegia, optic atrophy, and neuropathy (SPOAN) is an autosomal recessive neurodegenerative disorder characterized by early-onset progressive spastic paraplegia resulting in loss of independent ambulation in the teenage years. Additional features include optic atrophy, later onset of sensorimotor peripheral neuropathy, and progressive joint contractures; cognition remains intact (summary by Melo et al., 2015). Clinical Features Macedo-Souza et al. (2005) reported a large consanguineous Brazilian family in which 25 members had a neurologic disorder characterized by congenital optic atrophy, early-onset progressive spastic paraplegia, and distal axonal motor and sensory peripheral neuropathy (SPOAN). Affected patients showed mild motor developmental delay early in life with loss of independent ambulation by 10 years of age; 3 patients never achieved ambulation.
McGillivray syndrome Other names Familial scaphocephaly syndrome, McGillivray type, Scaphocephaly-macrocephaly-maxillary retrusion-intellectual disability syndrome This condition is inherited via an autosomal dominant manner Specialty Cardiology McGillivray syndrome is a rare syndrome characterized mainly by heart defects , skull and facial abnormalities and ambiguous genitalia . The symptoms of this syndrome are ventricular septal defect , patent ductus arteriosus , small jaw, undescended testes , and webbed fingers. ... If the doctor suspects the baby's misshapen skull is caused by an underlying hereditary syndrome, genetic testing may help identify the syndrome. ... Rare types [ edit ] There are two less common types of McGillivray syndromes are: Metopic synostosis ( trigonocephaly ). ... Johns Hopkins Hospital, n.d. Web. "Symptoms of McGillivray Syndrome." - RightDiagnosis.com. N.p., n.d.
Clinical Features McGillivray et al. (2005) reported a 3-generation family in which 11 members showed autosomal dominant inheritance of a distinct craniosynostosis syndrome characterized by scaphocephaly, macrocephaly, hypertelorism, maxillary retrusion, and mild intellectual disability. The authors noted that the absence of shallow orbits and ocular proptosis in this kindred excluded the diagnosis of Crouzon syndrome (123500). Molecular Genetics In a 3-generation family with a scaphocephaly syndrome, McGillivray et al. (2005) screened for mutations in genes known to be associated with craniosynostosis and identified a mutation in the FGFR2 gene (176943.0034). McGillivray et al. (2005) stated that this was the first report of a pathogenic mutation in a craniosynostosis syndrome manifesting predominantly as scaphocephaly.
Familial scaphocephaly syndrome, McGillivray type is a rare newly described craniosynostosis (see this term) syndrome characterized by scaphocephaly, macrocephaly, severe maxillary retrusion, and mild intellectual disability.
"Incidence and risk factors for immune reconstitution inflammatory syndrome during highly active antiretroviral therapy". ... "Cryptococcus-Related Immune Reconstitution Inflammatory Syndrome (IRIS): Pathogenesis and its Clinical Implications" . ... "Pathology in euthermic bats with white nose syndrome suggests a natural manifestation of immune reconstitution inflammatory syndrome" . ... "Immune Reconstitution Inflammatory Syndrome (IRIS)" . Dermatology . p. 1378. ... External links [ edit ] "Immune Reconstitution Syndrome" at TheBody.com (by Nicholas Cheonis, Winter 2004/2005)
Mutation in the same gene causes Marfan syndrome (154700), of which ectopia lentis is a feature. ... Citing the revised Ghent criteria for Marfan syndrome, Loeys et al. (2010) proposed the designation 'ectopia lentis syndrome' (ELS) for patients with ectopia lentis and a mutation in the FBN1 gene who lack aortic involvement, to highlight the systemic nature of the condition and to emphasize the need for assessment of features outside the ocular system (see DIAGNOSIS). ... Further uncertainty as to whether families with seemingly isolated ectopia lentis represent an entity separate from the Marfan syndrome arose from the findings of Tsipouras et al. (1992): in 2 families, the isolated ectopia lentis was linked to the fibrillin gene (FBN1; 134797) on chromosome 15, the same gene to which Marfan syndrome is linked. ... Loeys et al. (2010) stated that the presence of a personal or family history of aortic aneurysm, or the identification of an FBN1 mutation previously associated with aortic aneurysm, would be sufficient to transition a patient's diagnosis to Marfan syndrome. They also suggested that to ensure vigilance of other organ systems, the diagnosis of ectopia lentis syndrome should not be formally invoked before 20 years of age. ... They stated that analysis of recurrent mutations and of affected family members of probands with only 1 major clinical criterion argued for a clinical continuum between such phenotypes and classic Marfan syndrome. Aragon-Martin et al. (2010) analyzed the FBN1 gene in 36 UK patients with ectopia lentis who did not fulfill the Ghent criteria for Marfan syndrome and identified causative mutations in 23 (64%).
Isolated ectopia lentis (IEL) is a genetic disorder that affects the positioning of the lens in the eyes. In individuals with IEL, the lens in one or both of the eyes is off-center. Symptoms of IOL usually present in childhood and may include vision problems such as nearsightedness ( myopia ), blurred vision ( astigmatism ), clouding of the lenses (cataracts), and increased pressure in the eyes (glaucoma). In some individuals, IEL can progress to retinal detachmen t (tearing of the back lining of the eye). IEL is caused by mutations in either the FBN1 or ADAMTSL4 gene. When caused by a mutation in the FBN1 gene, IEL is inherited in an autosomal dominant manner.
All patients were of normal stature and none had features of Marfan (154700) or Weill-Marchesani syndromes (277600). Echocardiography was normal in the 2 patients who were studied, and plasma homocysteine levels were normal in the 2 patients tested.
Ectopia lentis is a hallmark of several well-known syndromes, e.g., Marfan syndrome (154700), Weill-Marchesani syndrome (see 277600), and homocystinuria (236200).
Differential diagnosis Patients with IEL by definition do not have associated systemic abnormalities, although cardiac and skeletal examinations should be performed to help exclude Marfan syndrome (diagnosed according to the Ghent criteria) (see this term). Ectopia lentis is also a feature of homocystinuria, sulfite oxidase deficiency, Weill-Marchesani syndrome, aniridia, and Knobloch syndrome (see these terms), as well as pseudoexfoliation.
Unsourced material may be challenged and removed. Find sources: "Caplan's syndrome" – news · newspapers · books · scholar · JSTOR ( May 2008 ) ( Learn how and when to remove this template message ) Caplan's syndrome Other names Rheumatoid pneumoconiosis Specialty Rheumatology Caplan's syndrome (or Caplan disease or rheumatoid pneumoconiosis [1] ) is a combination of rheumatoid arthritis (RA) and pneumoconiosis that manifests as intrapulmonary nodules, which appear homogenous and well-defined on chest X-ray . [2] Contents 1 Signs and symptoms 2 Causes 3 Pathophysiology 4 Diagnosis 5 Management 6 Prognosis 7 Epidemiology 8 History 9 References 10 External links Signs and symptoms [ edit ] Caplan syndrome presents with cough and shortness of breath in conjunction with features of rheumatoid arthritis, such as painful joints and morning stiffness. ... Histologically, they usually have a necrotic center surrounded by a zone of plasma cells and lymphocytes, and often with a peripheral inflammatory zone made of macrophages and neutrophils. Causes [ edit ] Caplan syndrome occurs only in patients with both RA and pneumoconiosis related to mining dust (coal, asbestos, silica). ... It has also been shown to occur in cases of complicated silicosis (marked by progressive massive pneumoconiosis). History [ edit ] The syndrome is named after Dr. Anthony Caplan, a physician on the Cardiff Pneumoconiosis Panel, who identified the constellation of findings as a distinct entity in a 1953 publication. [4] He followed this with further articles exploring the disease. [5] [6] Caplan syndrome was originally described in coal miners with progressive massive fibrosis . ... ISBN 978-1-4160-4710-0 . ^ Ondrasík M (1989). "Caplan syndrome". Baillière's Clinical Rheumatology . 3 (1): 205–10. doi : 10.1016/S0950-3579(89)80045-7 . ... Withey (September 1962). "A Broader Concept of Caplan Syndrome Related to Rheumatoid Factors" .
Phantom vibration syndrome or phantom ringing syndrome is the perception that one's mobile phone is vibrating or ringing when it is not. ... S.; Visintainer, P. (2010). "Phantom vibration syndrome among medical staff: a cross sectional survey" . ... Retrieved 2019-02-11 . ^ Hills, Megan C. "Phantom Ringing Syndrome Is The Weird AF Condition You've Had But Never Heard Of" . ... Retrieved 2019-02-11 . ^ " " Phantom vibration syndrome" common in cellphone users" . www.cbsnews.com . ... Retrieved October 16, 2013 . ^ Wilson, Aidan (February 7, 2013). "Phantom vibration syndrome: Word of the Year" . Crikey.com.au .
D., & Nuti, A. (2013). Delusional Misidentification Syndromes and Dementia: A Border Zone Between Neurology and Psychiatry. ... The dangerousness of persons with misidentification syndromes. Bulletin of the American Academy of Psychiatry & the Law, 20(1), 77-86. ^ a b c d De Pauw, K. ... Dangerous delusions: Violence and the misidentification syndromes. The British Journal of Psychiatry, 152, 91-96. ^ a b c d e f g h i Förstl, H., Almeida, O., Owen, A., Burns, A., & Howard, R. (1991). Psychiatric, neurological and medical aspects of misidentification syndromes: A review of 260 cases. Psychological Medicine, 21(4), 905-910. ^ a b c d e f g h i j k l m n o p q Klein, C. ... The delusional misidentification syndromes: Strange, fascinating, and instructive.
Solitary rectal ulcer syndrome can cause rectal bleeding and straining during bowel movements. Despite the name, sometimes more than one rectal ulcer occurs in solitary rectal ulcer syndrome. Solitary rectal ulcer syndrome may improve with simple lifestyle strategies, such as changing your diet and drinking more fluids. ... Several other conditions may cause signs and symptoms similar to those of solitary rectal ulcer syndrome. At your appointment, your doctor may recommend tests and procedures to identify or rule out causes other than solitary rectal ulcer syndrome. ... Treatment Treatment for solitary rectal ulcer syndrome depends on the severity of your condition. ... Surgical procedures used to treat solitary rectal ulcer syndrome include: Rectal prolapse surgery.
Solitary rectal ulcer syndrome (SRUS) is a rare rectal disease characterized by rectal bleeding, abdominal pain, passage of mucus, sensation of incomplete evacuation, straining at defecation and rectal prolapsed, secondary to ischemic changes in the rectum.
Wolcott–Rallison syndrome Other names Early-onset diabetes mellitus with multiple epiphyseal dysplasia Radiograph of a WRS child presenting with dysplastic bone growth in various regions of the body. ... "Wolcott-Rallison syndrome with 3-hydroxydicarboxylic aciduria and lethal outcome". ... "Frequency and spectrum of Wolcott-Rallison syndrome in Saudi Arabia: a systematic review" . ... S2CID 12244157 . ^ a b Julier C, Nicolino M (November 2010). "Wolcott-Rallison syndrome" . Orphanet Journal of Rare Diseases . 5 (1): 29. doi : 10.1186/1750-1172-5-29 . ... Ketoacidosis in Neonatal Diabetes Mellitus, Part of Wolcott-Rallison Syndrome. The American Journal of Case Reports, 18, 719–722. http://www.amjcaserep.com/abstract/index/idArt/902804 External links [ edit ] Media related to Wolcott–Rallison syndrome at Wikimedia Commons Classification D ICD - 10 : E13 OMIM : 226980 MeSH : C536739 External resources Orphanet : 1667
Description Wolcott-Rallison syndrome is a rare autosomal recessive disorder characterized by permanent neonatal or early infancy insulin-dependent diabetes. ... Al-Gazali et al. (1995) described this syndrome in 2 brothers born to consanguineous Omani parents. ... Stewart et al. (1996) suggested that a gene for Wolcott-Rallison syndrome may lie in the region 15q11-q12. Mapping On the basis of 2 consanguineous families, Delepine et al. (2000) mapped the Wolcott-Rallison syndrome locus, which they symbolized WRS, to a region of less than 3 cM on chromosome 2p12. ... In one of the sibs with Wolcott-Rallison syndrome reported by Al-Gazali et al. (1995), Brickwood et al. (2003) identified a splice site mutation in the EIF2AK3 gene (604032.0003).
Wolcott-Rallison syndrome (WRS) is a very rare genetic disease, characterized by permanent neonatal diabetes mellitus (PNDM) with multiple epiphyseal dysplasia and other clinical manifestations, including recurrent episodes of acute liver failure. ... That of NDM (see this term) includes transient NDM, and other PNDMs that may be isolated or syndromic. Differential diagnosis of skeletal dysplasia includes other spondylo-epiphyseal dysplasias such as mucopolysaccharidoses (see these terms) where diabetes may occur independently at an older age.
A rare genetic skeletal muscle disease characterized by abnormal chimeric aggregates of desmin and other cytoskeletal proteins and granulofilamentous material at the ultrastructural level in muscle biopsies and variable clinical myopathological features, age of disease onset and rate of disease progression. Patients present with bilateral skeletal muscle weakness that starts in distal leg muscles and spreads proximally, sometimes involving trunk, neck flexors and facial muscles and often cardiomyopathy manifested by conduction blocks, arrhythmias, chronic heart failure, and sometimes tachyarrhythmia. Weakness eventually leads to wheelchair dependence. Respiratory insufficiency can be a major cause of disability and death, beginning with nocturnal hypoventilation with oxygen desaturation and progressing to daytime respiratory failure.
'Desmin-related myopathy' is another term referring to MFM in which there are intrasarcoplasmic aggregates of desmin, usually in addition to other sarcomeric proteins. Rigid spine syndrome (602771), caused by mutation in the SEPN1 gene (606210), is another desmin-related myopathy. ... Two of the men had a pacemaker implanted because of atrial ventricular block and sick sinus syndrome (see 608567). Inheritance was autosomal dominant with variable onset and severity of skeletal muscle and cardiac involvement.
Myofibrillar myopathy is part of a group of disorders called muscular dystrophies that affect muscle function and cause weakness. Myofibrillar myopathy primarily affects skeletal muscles, which are muscles that the body uses for movement. In some cases, the heart (cardiac) muscle is also affected. The signs and symptoms of myofibrillar myopathy vary widely among affected individuals, typically depending on the condition's genetic cause. Most people with this disorder begin to develop muscle weakness (myopathy) in mid-adulthood. However, features of this condition can appear anytime between infancy and late adulthood.
A number sign (#) is used with this entry because of evidence that Rapp-Hodgkin syndrome is caused by heterozygous mutation in the TP63 gene (603273) on chromosome 3q27. Allelic disorders with overlapping features include EEC3 (604292), limb-mammary syndrome (LMS; 603543), ADULT syndrome (103285), AEC syndrome (106260), and SHFM4 (605289). ... The association of ankyloblepharon, ectodermal defects, and clefting (106260) is referred to as the AEC syndrome or Hay-Wells syndrome. See also 106250 for the association of ankyloblepharon with cleft palate. ... In 2 unrelated patients with features consistent with Rapp-Hodgkin syndrome, Bougeard et al. (2003) identified heterozygosity for mutations in the TP63 gene, R279H (603273.0007) and 1709delA (603273.0016), respectively. ... In a 42-year-old woman and her mother, who had Rapp-Hodgkin syndrome associated with Groenouw-type corneal dystrophy (see 121900) and premature menopause at ages 28 and 35 years, respectively, Holder-Espinasse et al. (2007) identified heterozygosity for a 1-bp deletion in the TP63 gene (603273.0025).
For a phenotypic description and a discussion of genetic heterogeneity of nonsyndromic cleft lip/palate (CL/P), see 119530. Mapping Stein et al. (1995) tested linkage of 22 candidate genes to CL/P in 11 multigenerational families, and excluded 21 of these candidates. APOC2 (608083), which is located at 19q13.1 (or 19q13.2) and which is linked to the protooncogene BCL3 (109560), gave suggestive evidence for linkage to CL/P. The study was expanded to include a total of 39 multigenerational CL/P families. Linkage was tested in all the families, using an anonymous marker, D19S178, and intragenic markers in BCL3 and APOC2.
Neiswanger et al. (2009) suggested that whorl lip print patterns might be part of an expanded phenotypic spectrum of nonsyndromic CL/P. Inheritance Over 200 syndromes, including a number that are either chromosomal or mendelian in causation, have cleft lip and/or palate as feature(s) (Gorlin, 1982). ... Curtis et al. (1961) estimated that the risk of recurrence of CL/P in subsequently born children is 4% if one child has it, 4% if one parent has it, 17% if one parent and one child have it, and 9% if two children have it. The syndrome of cleft lip with or without cleft palate in association with mucous pits of the lower lip is inherited as an autosomal dominant (119300). ... Patients of the 1920-1939 period traced through a child, either normal or affected, were excluded, as were patients with recognized syndromes. The proportion affected of children of probands was 3.15%, of sibs 2.79%, and of parents 1.18%. ... The genes were selected based on expression patterns, animal models, and/or role in known human clefting syndromes. For 7 genes with identified coding mutations that are potentially etiologic, they performed linkage disequilibrium studies as well in 501 family triads (affected child/mother/father). ... INHERITANCE - Autosomal dominant HEAD & NECK Mouth - Nonsyndromic cleft lip with or without cleft palate MISCELLANEOUS - Genetic heterogeneity, probably determined by major and minor genes, environmental factors, and developmental threshold - Divided into isolated cases (75-80%), familial (10-15%), and syndromal (1-5%) MOLECULAR BASIS - Caused by mutation in the homolog of the Drosophila muscle segment homeo box (MSX1, 142983.0004 ) ▲ Close
A number sign (#) is used with this entry because of evidence that orofacial cleft-8 (OFC8) is caused by heterozygous mutation in the TP63 gene (603273) on chromosome 3q28. Clinical Features Leoyklang et al. (2006) reported a 4-year-old Thai girl with a surgically repaired bilateral complete cleft lip. Her parents were unaffected. Basha et al. (2018) reported a family (CLP-1055) in which the proband and his father had orofacial cleft. The son had a unilateral, right-sided cleft lip. He had no limb anomaly, no ectodermal dysplasia, and no cardiac malformations. Follow-up until the age of 3.5 years showed growth and development within normal limits.
The biologic mechanisms of mutual recognition of the two cabinets, and the way they are glued together, are quite complex and obscure despite intensive scientific research. [31] Orofacial clefts may be associated with a syndrome (syndromic) or may not be associated with a syndrome (nonsyndromic). Syndromic clefts are part of syndromes that are caused by a variety of factors such as environment and genetics or an unknown cause. Nonsyndromic clefts, which are not as common as syndromic clefts, also have a genetic cause. [32] Genetics Genetic factors contributing to cleft lip and cleft palate formation have been identified for some syndromic cases. Many clefts run in families, even though in some cases there does not seem to be an identifiable syndrome present. [33] A number of genes are involved including cleft lip and palate transmembrane protein 1 and GAD1 , [34] One study found an association between mutations in the HYAL2 gene and cleft lip and cleft palate formation. [35] Syndromes The Van der Woude syndrome is caused by a specific variation in the gene IRF6 that increases the occurrence of these deformities threefold. [36] [37] [38] Mutations in interferon regulatory factor 6 (IRF6) that cause cleft lip palate are also implicated in neural tube defects such as spina bifida. [39] Another syndrome, Siderius X-linked intellectual disability , is caused by mutations in the PHF8 gene ( OMIM : 300263 ); in addition to cleft lip or palate, symptoms include facial dysmorphism and mild mental retardation. [40] In some cases, cleft palate is caused by syndromes that also cause other problems: Stickler syndrome can cause cleft lip and palate, joint pain, and myopia . [41] [42] Loeys–Dietz syndrome can cause cleft palate or bifid uvula , hypertelorism , and aortic aneurysm . [43] Hardikar syndrome can cause cleft lip and palate, Hydronephrosis , Intestinal obstruction and other symptoms. [44] Cleft lip/palate may be present in many different chromosome disorders including Patau syndrome (trisomy 13). Malpuech facial clefting syndrome Hearing loss with craniofacial syndromes Popliteal pterygium syndrome Cornelia de Lange syndrome Treacher Collins syndrome Pierre Robin syndrome [45] [32] Specific genes Type OMIM Gene Locus OFC1 119530 ?
For a phenotypic description and a discussion of genetic heterogeneity of nonsyndromic cleft lip/palate (CL/P), see 119530. Mapping Using 13 microsatellite markers specific for 4q in a study of 7 of 8 persons with CL/P in a 5-generation family, Beiraghi et al. (1994) found evidence of linkage between the phenotype and 2 markers, D4S175 (maximum lod = 2.27 at theta = 0) and D4S192 (maximum lod = 1.93 at theta = 0). No linkage with markers on chromosome 6 was found in this family. In linkage studies of 36 multiplex Chinese families with CL/P, Marazita et al. (2002) found the highest multipoint heterogeneity lod score (2.5) at 4q with marker D4S1629 under a recessive inheritance model. In addition, there was a positive identity-by-descent result with D4S2361. Cytogenetics In a father and son with cleft lip, Beiraghi et al. (2003) identified a balanced pericentric inversion of chromosome 4, inv(4)(p13q21).
For a phenotypic description and a discussion of genetic heterogeneity of nonsyndromic cleft lip/palate (CL/P), see 119530. Mapping Ardinger et al. (1989) observed a significant association between 2 RFLPs at the transforming growth factor-alpha (TGFA; 190170) locus on chromosome 2p13 and the occurrence of clefting. The authors suggested that either the TGFA gene or DNA sequences adjacent to the locus contribute to the development of some cases of cleft lip with or without cleft palate in humans. However, in a study of 7 families with CL/P segregating in a dominant manner, the TGFA haplotype associations reported by Ardinger et al. (1989) were not seen, and in 1 family clefting did not cosegregate with TGFA, thus ruling out tight linkage (Hecht et al. (1990, 1991)). In 96 unrelated patients with nonsyndromic CL/P, Chenevix-Trench et al. (1991) confirmed the existence of an excess frequency of the same TaqI allele found by Ardinger et al. (1989).
A number sign (#) is used with this entry because of evidence that orofacial cleft-11 (OFC11) is caused by heterozygous mutation in the BMP4 gene (112262) on chromosome 14q22. For a phenotypic description and a discussion of genetic heterogeneity of nonsyndromic cleft lip with or without cleft palate, see OFC1 (119530). Description Congenital 'healed' cleft lip (CHCL) is an unusual anomaly consisting of a paramedian 'scar' of the upper lip with an appearance suggesting that a typical cleft lip was corrected in utero. The CHCL is frequently associated with an ipsilateral notch in the vermilion border and a 'collapsed' nostril (Castilla and Martinez-Frias, 1995). Clinical Features Castilla and Martinez-Frias (1995) presented 25 CHCL cases, 18 of which represented an isolated malformation found among the 3,950,715 births examined in 2 similar birth defect registries, 1 in Spain and 1 in Latin America.
A number sign (#) is used with this entry because of evidence that cleft lip/palate-ectodermal dysplasia syndrome (CLPED1) is caused by homozygous mutation in the PVRL1 gene (NECTIN1; 600644) on chromosome 11q23. ... In 3 Brazilian brothers and a half brother, all born of first-cousin matings in a Brazilian kindred, Rodini and Richieri-Costa (1990) described a syndrome which they proposed to call the Zlotogora-Ogur syndrome on the basis of the reports by Zlotogora et al. (1987) and Ogur and Yuksel (1988). ... Zlotogora (1994) gave a review of the syndrome of syndactyly, ectodermal dysplasia, and cleft lip/palate in which he proposed that the disorder called Zlotogora-Ogur syndrome (Zlotogora and Ogur, 1988) is the same as that reported by Bustos et al. (1991) and referred to here as the Margarita form of ectodermal dysplasia. Mental retardation was present in those families described as having Zlotogora-Ogur syndrome but absent in the Margarita families. ... In 2 families from Israel and Brazil described as having Zlotogora-Ogur syndrome, Suzuki et al. (2000) also found homozygous mutations in the PVRL1 gene (600644.0002-600644.0003).
A number sign (#) is used with this entry because of evidence that orofacial cleft-10 (OFC10) is caused by mutation in the SUMO1 gene (601912) on chromosome 2q33. One such patient has been reported. For a phenotypic description and a discussion of genetic heterogeneity of nonsyndromic cleft lip/palate (CL/P), see 119530. Clinical Features Alkuraya et al. (2006) identified a 5-year-old Caucasian girl with a unilateral cleft lip and palate (primary and secondary) who was otherwise phenotypically normal. Her karyotype was 46,XX,t(2;8)(q33.1;q24.3), and array CGH analysis was normal. Molecular Genetics Alkuraya et al. (2006) showed that the balanced translocation in a girl with orofacial cleft disrupted the SUMO1 gene, leading to haploinsufficiency confirmed by RNA and protein studies (601912.0001).
Analysis of DLX4 in 3 patients with blepharocheilodontic syndrome (see 119580) and in 155 patients with nonsyndromic CL, CL/P, or CP did not reveal any mutations.
They most commonly occur as isolated birth defects but are also associated with many inherited genetic conditions or syndromes. Having a baby born with a cleft can be upsetting, but cleft lip and cleft palate can be corrected. ... The mother or the father can pass on genes that cause clefting, either alone or as part of a genetic syndrome that includes a cleft lip or cleft palate as one of its signs. ... The fluid test may indicate that the fetus has inherited a genetic syndrome that may cause other birth defects.
For a phenotypic description and a discussion of genetic heterogeneity of nonsyndromic CL/P, see 119530. Mapping In van der Woude syndrome (VWS; 119300), lower lip pits are associated with CL/P or cleft palate only. ... By linkage studies, Hecht et al. (1992) excluded the region of chromosome 1q which carries the van der Woude syndrome as the site of the mutation in this disorder and in isolated cleft palate. ... INHERITANCE - Autosomal dominant HEAD & NECK Mouth - Cleft lip, isolated - Cleft palate, isolated - Cleft lip and cleft palate MISCELLANEOUS - Genetic heterogeneity (see OFC1, 119530 ) - Allelic disorder to van der Woude syndrome (VWS, 119300 ) and popliteal pterygium syndrome (PPS, 119500 ) MOLECULAR BASIS - Susceptibility conferred by mutation in the interferon regulatory factor 6 gene (IRF6, 607199.0013 ) ▲ Close
Cleft lip and palate is an isolated, non-syndromic anomaly in 70% of cases and the remaining 30% of cases are seen in about 300 syndromes. Non-syndromic clefts are believed to be caused by a combination of genetic and environmental factors. ... Differential diagnosis The presence of associated malformations allows for differentiation between isolated and syndromic forms. Antenatal diagnosis Antenatal diagnosis is often made during prenatal ultrasound.
For a phenotypic description and a discussion of genetic heterogeneity of nonsyndromic CL/P, see 119530. Mapping Birnbaum et al. (2009) conducted a genomewide association study involving 224 unrelated patients of Central European origin with nonsyndromic cleft lip with or without cleft palate (NSCL/P) and identified a 640-kb region on chromosome 8q24.21 containing 3 markers that reached genomewide significance. Fine mapping of the 640-kb region in 462 unrelated NSCL/P cases revealed a SNP (rs987525) that was significantly associated with the disorder (p = 3.34 x 10(-24); odds ratio, 2.57 for heterozygotes and 6.05 for homozygotes). The calculated population attributable risk for this marker was 0.41, suggesting that this represents a major susceptibility locus for NSCL/P. In independent Estonian and Lithuanian samples, Nikopensius et al. (2009) replicated the previously reported association between rs987525 and nonsyndromic oral clefting, obtaining highly significant results in both groups (p = 5.97 x 10(-5) and p = 1.6 x 10(-5), respectively).
For a phenotypic description and a discussion of genetic heterogeneity of nonsyndromic cleft lip/palate (CL/P), see 119530. Mapping In 2 Indian pedigrees with isolated, nonsyndromic cleft lip with or without cleft palate segregating as an autosomal dominant trait, Radhakrishna et al. (2006) demonstrated linkage to 13q33.1-q34, with a nonparametric linkage score of 5.57 at marker rs1830756. Haplotype analysis with informative crossovers enabled the mapping of a CL/P locus to a region of approximately 20.17 cM (7.42 Mb) between SNPs rs951095 and rs726455. The phenotype was variable, ranging from unilateral to bilateral CL/P. The authors noted that CL/P is very common in patients with trisomy involving all or part of chromosome 13 (Berge et al., 2001).
A number sign (#) is used with this entry because of evidence that orofacial cleft-5 (OFC5) is caused by mutation in the MSX1 gene (142983) on chromosome 4p16. For a phenotypic description and a discussion of genetic heterogeneity of nonsyndromic CL/P, see 119530. Molecular Genetics With both case-control- and nuclear family-based approaches, Lidral et al. (1998) screened candidate genes for clefting in both the CL/P CPO of the nonsyndromic type. Significant linkage disequilibrium was found between CL/P and both MSX1 and TGFB3 (190230) and between CPO and MSX1, suggesting that these genes are involved in the pathogenesis of clefting. In addition, a mutation search in the genes DLX2 (126255), MSX1, and TGFB3 was performed in 69 CPO patients and in a subset of CL/P patients.
Mutations in the EVC and EVC2 genes cause Ellis-van Creveld syndrome (225500), an allelic disorder with autosomal recessive inheritance. ... Weyers (1956) was aware of similarities to the Ellis-van Creveld syndrome. Roubicek and Spranger (1984) reported an affected 4-generation family. ... In vitro studies in NIH3T3 cells showed that the Hedgehog signaling pathway is fully active in cells mimicking EVC syndrome mutations but is impaired in cells mimicking WAD mutations. ... Nomenclature Confusion has been generated by the use of the Weyers eponym with this disorder and with Weyers ulnar ray oligodactyly syndrome (602418), as well as with the Weyers oculovertebral syndrome. The use of the term Weyers syndrome (without further qualification) should be discontinued for this reason (Biesecker, 1995).
A rare ectodermal dysplasia syndrome with bone abnormalities characterized by onychodystrophy; anomalies of the lower jaw, oral vestibule and dentition; post-axialpolydactyly; moderately restricted growth with short limbs; and normal intelligence. Although it closely resembles Ellis-van Creveld syndrome (see this term), an allelic disorder and another type of ciliopathy, WAD is usually a milder disease without the presence of heart abnormalities and is inherited in an autosomal dominant manner.
The features of Weyers acrofacial dysostosis overlap with those of another, more severe condition called Ellis-van Creveld syndrome. In addition to tooth and nail abnormalities, people with Ellis-van Creveld syndrome have very short stature and are often born with heart defects.
Nuclear factor-kappa B Essential Modulator (NEMO) deficiency syndrome is a rare type of primary immunodeficiency disease that has a highly variable set of symptoms and prognoses. ... In some severely affected patients, NEMO deficiency syndrome is treated using a bone marrow or blood stem cell transplant. ... "Persistent systemic inflammation and atypical enterocolitis in patients with NEMO syndrome" . Clinical Immunology (Orlando, Fla.) . 132 (1): 124–31. doi : 10.1016/j.clim.2009.03.514 . ... PMID 19375390 . ^ NEMO deficiency syndrome information , Great Ormond Street Hospital for Children ^ a b "NEMO deficiency syndrome" . ... PMC 5268070 . ^ "NEMO deficiency syndrome" . Great Ormond Street Hospital for Children .