The authors suggested that BFIS2, PKC, and ICCA syndrome may be allelic disorders. Alternatively, they suggested that homologous genes may have arisen through duplication in this region of chromosome 16 which may be responsible for nonallelic disorders. ... Heterozygous mutations in the PRRT2 gene were also found in 5 (83%) of 6 families with familial infantile convulsions with paroxysmal choreoathetosis (ICCA; 602066), a familial syndrome in which infantile seizures and an adolescent-onset movement disorder, paroxysmal kinesigenic choreoathetosis (EKD1; 128200), cooccur.
For a phenotypic description and a discussion of genetic heterogeneity of benign neonatal seizures, see BFNS1 (121200). Clinical Features Schiffmann et al. (1991) described an Iranian Jewish kindred in which 4 children of the same generation in 2 separate sibships with complex parental consanguinity had neonatal seizures. Linkage analysis excluded assignment to the BFNS1 locus on chromosome 20q. Inheritance The transmission pattern of benign neonatal seizures in the family reported by Schiffmann et al. (1991) suggested autosomal recessive inheritance. INHERITANCE - Autosomal recessive NEUROLOGIC Central Nervous System - Seizures, generalized tonic-clonic - Hypertonia in neonatal period - Normal interictal EEG - Normal psychomotor development - Patients may develop a seizure disorder later in life MISCELLANEOUS - Onset at 6-36 hours of life - Seizures resolve by 4 months of age - See EBN1 ( 121200 ) for an autosomal dominant form ▲ Close
Deprez et al. (2009) provided a review of the genetics of epilepsy syndromes starting in the first year of life, and included a diagnostic algorithm. ... Zimprich et al. (2006) provided a historical perspective of the work of Andreas Rett (1924-1997), a pediatric neurologist and social reformer in postwar Austria, who first described BFNC and later delineated Rett syndrome (312750). INHERITANCE - Autosomal dominant RESPIRATORY - Apnea during seizures NEUROLOGIC Central Nervous System - Seizures, afebrile - Focal clonic seizures - Generalized tonic-clonic seizures - Start with tonic posturing - Motor automatisms - Febrile seizures may occur - Increased risk of seizures in childhood or adulthood (11-16%) - Normal psychomotor development - Epileptic encephalopathy with psychomotor retardation (rare) - Drug-resistent seizures (rare) - Myokymia - Finger twitching - EMG with spontaneous discharge of normal motor unit potentials MISCELLANEOUS - Onset of seizures at 2-8 days of life - Most remit by 6 weeks (1-6 months) - Variable phenotype - Some patients may have isolated myokymia - Genetic heterogeneity (see EBN2 121201 , EBN3 608217 ) - An autosomal recessive form has been reported ( 269720 ) MOLECULAR BASIS - Caused by mutation in the potassium voltage-gated channel, KQT-like subfamily, member 2 gene (KCNQ2, 602235.0001 ) ▲ Close
A number sign (#) is used with this entry because benign familial neonatal seizures-2 (BFNS2) is caused by heterozygous mutation in the KCNQ3 gene (602232) on chromosome 8q24. Description Benign familial neonatal seizures-2 is an autosomal dominant neurologic condition characterized by onset of clonic or tonic-clonic seizures in the first few days of life. Seizures tend to last for about a minute, may occur several times a day, and are responsive to medication. Almost all patients have full remission within the first months of life, although some rare patients may have a few seizures later in childhood. EEG, brain imaging, and psychomotor development are usually normal (summary by Fister et al., 2013).
Benign familial neonatal-infantile seizures (BFNIS) is a benign familial epilepsy syndrome with an intermediate phenotype between benign familial neonatal seizures (BFNS) and benign familial infantile seizures (BFIS; see these terms). So far, this syndrome has been described in multiple members of 10 families.
The authors noted that the breakpoint was different from that found in cri-du-chat syndrome (123450). INHERITANCE - Autosomal dominant NEUROLOGIC Central Nervous System - Seizures, generalized tonic-clonic MISCELLANEOUS - Onset in first months of life - Seizures usually remit spontaneously by 12 months of age - No neurologic sequelae ▲ Close
For a general phenotypic description and a discussion of genetic heterogeneity of benign familial infantile seizures, see BFIS1 (601764). Clinical Features Li et al. (2008) reported a 4-generation Chinese family in which 8 individuals had benign infantile seizures. Age at seizure onset ranged from 3 to 10 months of life. The proband developed afebrile seizures at age 6 months, characterized by staring, eye deviation, focal clonus of the face, followed by secondarily generalized phase with hypertonia, extremities clonus, cyanosis, and urinary incontinence. The seizures lasted from 30 seconds to 2 minutes and occurred mainly in clusters with 3 to 10 episodes per day. Interictal EEG, brain CT, and MRI were classified as normal. Treatment with sodium valproate was effective, and the proband's seizures spontaneously remitted by 3 years of age.
Benign familial infantile epilepsy (BFIE) is a genetic epileptic syndrome characterized by the occurrence of afebrile repeated seizures in healthy infants, between the third and eighth month of life. ... A family history of the same epilepsy is a constant finding. A syndrome called familial infantile convulsions and choreoathetosis (ICCA; see this term) has been observed in which BFIE patients present in childhood and/or adolescence with choreoathetotic dyskinetic attacks occurring spontaneously or following diverse stimuli (e.g. exercise, stress). ... Differential diagnosis Differential diagnosis includes benign familial neonatal-infantile seizures (see this term), an epileptic syndrome with an intermediate onset between the neonatal and infantile age that shares overlapping clinical characteristics with BFIE and that is mainly due to mutations in the SCN2A gene.
A number sign (#) is used with this entry because of evidence that benign familial infantile seizures-5 (BFIS5) is caused by heterozygous mutation in the SCN8A gene (600702) on chromosome 12q13. Heterozygous mutation in the SCN8A gene can also cause the more severe disorder EIEE13 (614558). Description Benign familial infantile seizures-5 (BFIS5) is an autosomal dominant neurologic disorder characterized by onset of afebrile seizures during infancy. In most cases, the seizures remit by age 2 years, although some patients may have single or a few seizures later in childhood. The seizures respond well to treatment with sodium channel blockers, and patients have normal subsequent psychomotor development.
Benign familial neonatal epilepsy (BFNE) is a rare genetic epilepsy syndrome characterized by the occurrence of afebrile seizures in otherwise healthy newborns with onset in the first few days of life. ... Later seizures have been reported, including occasional febrile seizures and idiopathic epilepsy syndromes in childhood, in particular Rolandic epilepsy.
A number sign (#) is used with this entry because benign familial neonatal-infantile seizures-3 (BFIS3) is caused by heterozygous mutation in the SCN2A gene (182390) on chromosome 2q24. See also early infantile epileptic encephalopathy-11 (EIEE11; 613721), a more severe disorder that also results from mutations in the SCN2A gene. Description Benign familial neonatal-infantile seizures is an autosomal dominant disorder in which afebrile seizures occur in clusters during the first year of life, without neurologic sequelae (Shevell et al., 1986). For a general phenotypic description and a discussion of genetic heterogeneity of benign familial infantile seizures, see BFIS1 (601764). BFIS1 has a slightly later onset than BFIS3, while benign neonatal seizures (see BFNS1, 121200) has a slightly earlier onset.
In situations where both parents have achondroplasia there is a 50% chance the child will have achondroplasia, 25% chance the child will not, and a 25% chance that the child will inherit the gene from both parents resulting in double dominance and leading to severe or lethal bone dysplasia. [11] Studies have demonstrated that new gene mutations for achondroplasia are exclusively inherited from the father and occur during spermatogenesis ; it has been theorized that sperm carrying the mutation in FGFR3 have a selective advantage over sperm with normal FGFR3. [4] The frequency of mutations in sperm leading to achondroplasia increase in proportion to paternal age, as well as in proportion to exposure to ionizing radiation . [12] The occurrence rate of achondroplasia in the children of fathers over 50 years of age is 1 in 1,875, compared to 1 in 15,000 in the general population. [13] Research by urologist Harry Fisch of the Male Reproductive Center at Columbia Presbyterian Hospital in 2013 indicated that in humans this defect may be exclusively inherited from the father and becomes increasingly probable with paternal age, specifically males reproducing after 35. [14] There are two other syndromes with a genetic basis similar to achondroplasia: hypochondroplasia and thanatophoric dysplasia . ... Another distinct characteristic of the syndrome is thoracolumbar gibbus in infancy. ... "The Molecular and Genetic Basis of Fibroblast Growth Factor Receptor 3 Disorders: The Achondroplasia Family of Skeletal Dysplasias, Muenke Craniosynostosis, and Crouzon Syndrome with Acanthosis Nigricans" . Endocrine Reviews . 21 (1): 23–39. doi : 10.1210/edrv.21.1.0387 . ... NBK1152. v t e Osteochondrodysplasia Osteodysplasia/ / osteodystrophy Diaphysis Camurati–Engelmann disease Metaphysis Metaphyseal dysplasia Jansen's metaphyseal chondrodysplasia Schmid metaphyseal chondrodysplasia Epiphysis Spondyloepiphyseal dysplasia congenita Multiple epiphyseal dysplasia Otospondylomegaepiphyseal dysplasia Osteosclerosis Raine syndrome Osteopoikilosis Osteopetrosis Other/ungrouped FLNB Boomerang dysplasia Opsismodysplasia Polyostotic fibrous dysplasia McCune–Albright syndrome Chondrodysplasia / chondrodystrophy (including dwarfism ) Osteochondroma osteochondromatosis Hereditary multiple exostoses Chondroma / enchondroma enchondromatosis Ollier disease Maffucci syndrome Growth factor receptor FGFR2 : Antley–Bixler syndrome FGFR3 : Achondroplasia Hypochondroplasia Thanatophoric dysplasia COL2A1 collagen disease Achondrogenesis type 2 Hypochondrogenesis SLC26A2 sulfation defect Achondrogenesis type 1B Autosomal recessive multiple epiphyseal dysplasia Atelosteogenesis, type II Diastrophic dysplasia Chondrodysplasia punctata Rhizomelic chondrodysplasia punctata Conradi–Hünermann syndrome Other dwarfism Fibrochondrogenesis Short rib – polydactyly syndrome Majewski's polydactyly syndrome Léri–Weill dyschondrosteosis v t e Cell surface receptor deficiencies G protein-coupled receptor (including hormone ) Class A TSHR ( Congenital hypothyroidism 1 ) LHCGR ( Luteinizing hormone insensitivity , Leydig cell hypoplasia , Male-limited precocious puberty ) FSHR ( Follicle-stimulating hormone insensitivity , XX gonadal dysgenesis ) GnRHR ( Gonadotropin-releasing hormone insensitivity ) EDNRB ( ABCD syndrome , Waardenburg syndrome 4a , Hirschsprung's disease 2 ) AVPR2 ( Nephrogenic diabetes insipidus 1 ) PTGER2 ( Aspirin-induced asthma ) Class B PTH1R ( Jansen's metaphyseal chondrodysplasia ) Class C CASR ( Familial hypocalciuric hypercalcemia ) Class F FZD4 ( Familial exudative vitreoretinopathy 1 ) Enzyme-linked receptor (including growth factor ) RTK ROR2 ( Robinow syndrome ) FGFR1 ( Pfeiffer syndrome , KAL2 Kallmann syndrome ) FGFR2 ( Apert syndrome , Antley–Bixler syndrome , Pfeiffer syndrome , Crouzon syndrome , Jackson–Weiss syndrome ) FGFR3 ( Achondroplasia , Hypochondroplasia , Thanatophoric dysplasia , Muenke syndrome ) INSR ( Donohue syndrome Rabson–Mendenhall syndrome ) NTRK1 ( Congenital insensitivity to pain with anhidrosis ) KIT ( KIT Piebaldism , Gastrointestinal stromal tumor ) STPK AMHR2 ( Persistent Müllerian duct syndrome II ) TGF beta receptors : Endoglin / Alk-1 / SMAD4 ( Hereditary hemorrhagic telangiectasia ) TGFBR1 / TGFBR2 ( Loeys–Dietz syndrome ) GC GUCY2D ( Leber's congenital amaurosis 1 ) JAK-STAT Type I cytokine receptor : GH ( Laron syndrome ) CSF2RA ( Surfactant metabolism dysfunction 4 ) MPL ( Congenital amegakaryocytic thrombocytopenia ) TNF receptor TNFRSF1A ( TNF receptor associated periodic syndrome ) TNFRSF13B ( Selective immunoglobulin A deficiency 2 ) TNFRSF5 ( Hyper-IgM syndrome type 3 ) TNFRSF13C ( CVID4 ) TNFRSF13B ( CVID2 ) TNFRSF6 ( Autoimmune lymphoproliferative syndrome 1A ) Lipid receptor LRP : LRP2 ( Donnai–Barrow syndrome ) LRP4 ( Cenani–Lenz syndactylism ) LRP5 ( Worth syndrome , Familial exudative vitreoretinopathy 4 , Osteopetrosis 1 ) LDLR ( LDLR Familial hypercholesterolemia ) Other/ungrouped Immunoglobulin superfamily : AGM3, 6 Integrin : LAD1 Glanzmann's thrombasthenia Junctional epidermolysis bullosa with pyloric atresia EDAR ( EDAR hypohidrotic ectodermal dysplasia ) PTCH1 ( Nevoid basal-cell carcinoma syndrome ) BMPR1A ( BMPR1A juvenile polyposis syndrome ) IL2RG ( X-linked severe combined immunodeficiency ) See also cell surface receptors
The fact that there are no reports of Wolf-Hirschhorn syndrome (194190) patients with stigmata of achondroplasia may indicate that the phenotype is due to some mechanism other than haploinsufficiency, e.g., represents a dominant-negative or gain-of-function effect. ... Total prevalence of autosomal dominant malformation syndromes was 12.1 per 100,000 live births.
In fact, there appears to be some overlap between the radiologic and clinical phenotypes of these two conditions [Almeida et al 2009]. Thanatophoric dysplasia SADDAN syndrome (OMIM 616482) Cartilage-hair hypoplasia (metaphyseal chondrodysplasia, McKusick type) Other metaphyseal dysplasias Pseudoachondroplasia (a clinically and genetically distinct skeletal dysplasia; but the similar nomenclature may cause confusion) Management Evaluations Following Initial Diagnosis Clinical manifestations in achondroplasia vary modestly.
A primary bone dysplasia with micromelia characterized by rhizomelia, exaggerated lumbar lordosis, brachydactyly, and macrocephaly with frontal bossing and midface hypoplasia. Epidemiology Achondroplasia estimated incidence is at about 1/25,000 live births worldwide. Clinical description Characteristic clinical features (short limbs with rhizomelia, long and narrow trunk and macrocephaly with frontal bossing and midfacial hypoplasia with depressed nasal bridge) are often times visible at birth. Hands are broad, short and trident shaped. Hypotonia is common, leading to hypermobile joints particularly in the lower extremities. A smaller foreamen magnum or abnormal shape can lead to serious sequelae in infancy like spinal cord compression or vertebral artery compression leading to central apnea.
Achondroplasia is a form of short-limbed dwarfism. The word achondroplasia literally means "without cartilage formation." Cartilage is a tough but flexible tissue that makes up much of the skeleton during early development. However, in achondroplasia the problem is not in forming cartilage but in converting it to bone (a process called ossification), particularly in the long bones of the arms and legs. Achondroplasia is similar to another skeletal disorder called hypochondroplasia, but the features of achondroplasia tend to be more severe. All people with achondroplasia have short stature. The average height of an adult male with achondroplasia is 131 centimeters (4 feet, 4 inches), and the average height for adult females is 124 centimeters (4 feet, 1 inch).
Achondroplasia is a disorder of bone growth that prevents the changing of cartilage (particularly in the long bones of the arms and legs) to bone. It is characterized by dwarfism , limited range of motion at the elbows, large head size (macrocephaly), small fingers, and normal intelligence. Achondroplasia can cause health complications such as interruption of breathing ( apnea ), obesity, recurrent ear infections, an exaggerated inward curve of the lumbar spine (lordosis). More serious problems include a narrowing of the spinal canal that can pinch (compress) the upper part of the spinal cord (spinal stenosis) and a buildup of fluid in the brain (hydrocephalus). Some people with achondroplasia may have delayed motor development early on, but cognition is normal.
Other disorders with sensory retinal early-onset nystagmus include autosomal dominant motor nystagmus, complete and incomplete achromatopsia, blue cone monochromacy, and other autosomal recessive stationary cone dysfunctions including enhanced S-cone syndrome, cone dystrophy with supernormal rod response, and Leber congenital amaurosis. ... A relation between this disorder and Waardenburg syndrome type 2 has been suggested and may result from digenic interaction between a transcription factor, MITF , and a missense pathogenic variant in TYR (encoding tyrosinase) [Morell et al 1997]. ... The disorder is possibly caused by an allelic GPR143 variant or a contiguous gene defect [Bassi et al 1999]. Hermansky-Pudlak Syndrome (HPS) is a multisystem disorder characterized by: tyrosinase-positive oculocutaneous albinism; a bleeding diathesis resulting from a platelet storage pool deficiency; and, in some cases, pulmonary fibrosis, granulomatous colitis, or immunodeficiency.
Cytogenetics Meindl et al. (1993) described the clinical features of a patient with a large Xp22.3 deletion who had ocular albinism in addition to short stature, chondrodysplasia punctata, mental retardation, ichthyosis, and Kallmann syndrome (KAL; 308700)--a total of 6 X-linked disorders. ... Both the mother and the sister of the patient were carriers of the deletion that showed a number of traits seen in Turner syndrome. The diagnosis of ocular albinism was confirmed in the patient and his mother, who showed iris translucency, patches and streaks of hypopigmentation in the fundus, and macromelanosomes in epidermal melanocytes. ... No additional clinical features that have been described with other deletion syndromes in this area were present. The STS locus was entirely deleted on Southern blots in the affected males, but the MIC2X (313470) and several anonymous DNA loci were not deleted.
Differential diagnosis Differential diagnoses include various types of oculocutaneous albinism (OCA), blue cone monochromatism, congenital stationary night blindness, ocular albinism with sensorineural deafness, cone dystrophy with supernormal rod response, Leber congenital amaurosis, complete and incomplete achromatopsia, X-linked congenital nystagmus (see these terms), and autosomal dominant infantile nystagmus syndrome. Antenatal diagnosis Prenatal testing can be performed when women are known carriers of the GPR143 mutation, using chorionic villus sampling or amniocentesis.
Ocular albinism type 1 (OA1) is a genetic eye condition that primarily affects males. Signs and symptoms may include reduced coloring of the iris and retina (ocular hypopigmentation); foveal hypoplasia (underdevelopment); rapid, involuntary eye movements (nystagmus); poor vision; poor depth perception; eyes that do not look in the same direction (strabismus); and increased sensitivity to light. It is caused by mutations in the GPR143 gene and is inherited in an X-linked recessive manner. Females have been affected in rare instances. Treatment consists of visual correction with eyeglasses or contact lenses; use of sunglasses or special filter glasses for light sensitivity; and in some cases, extraocular muscle surgery to restore alignment and/or improve head posture that is associated with nystagmus.
Ocular albinism is a genetic condition that primarily affects the eyes. This condition reduces the coloring (pigmentation) of the iris, which is the colored part of the eye, and the retina , which is the light-sensitive tissue at the back of the eye. Pigmentation in the eye is essential for normal vision. Ocular albinism is characterized by severely impaired sharpness of vision (visual acuity) and problems with combining vision from both eyes to perceive depth (stereoscopic vision). Although the vision loss is permanent, it does not worsen over time. Other eye abnormalities associated with this condition include rapid, involuntary eye movements (nystagmus); eyes that do not look in the same direction (strabismus); and increased sensitivity to light (photophobia). Many affected individuals also have abnormalities involving the optic nerves, which carry visual information from the eye to the brain.
Down syndrome (trisomy 21) [ edit ] Karyotype of trisomy 21 (Down syndrome) Note that chromosome 21 is present in 3 copies, while all other chromosomes show the normal diploid state with 2 copies. ... It is the leading cause of pregnancy wastage and is the most common known cause of mental retardation . [15] It is well documented that advanced maternal age is associated with greater risk of meiotic nondisjunction leading to Down syndrome. This may be associated with the prolonged meiotic arrest of human oocytes potentially lasting for more than four decades. [13] Edwards syndrome (trisomy 18) and Patau syndrome (trisomy 13) [ edit ] Human trisomies compatible with live birth, other than Down syndrome (trisomy 21), are Edwards syndrome (trisomy 18) and Patau syndrome (trisomy 13). [1] [2] Complete trisomies of other chromosomes are usually not viable and represent a relatively frequent cause of miscarriage. ... Formally, X chromosome monosomy ( Turner syndrome , see above) can also be classified as a form of sex chromosome aneuploidy. Klinefelter syndrome (47, XXY) [ edit ] Klinefelter syndrome is the most common sex chromosome aneuploidy in humans. ... Uniparental disomy of chromosome 15 is, for example, seen in some cases of Prader-Willi syndrome and Angelman syndrome . [14] Mosaicism syndromes [ edit ] Mosaicism syndromes can be caused by mitotic nondisjunction in early fetal development.
Clinical Features Hecht et al. (1964) reviewed evidence on the nonrandomness of chromosomal abnormalities, including Down syndrome (190685) and trisomy 18. Hirschhorn (1968) and Weiner (1965) reported familial mosaicism. ... The possibility of autosomal recessive genes predisposing to nondisjunction was examined by Kwiterovich et al. (1966), who determined the frequency of Down syndrome in an inbred Amish population, and by Matsunaga (1966), who investigated the frequency of consanguinity in the parents of cases of Down syndrome. These studies gave no suggestion of inbreeding effect in contrast to the work of Gowen (1933) indicating such an effect in Drosophila and suggestive earlier work with Down syndrome. Hirschhorn and Hsu (1969) and Hsu et al. (1970) described a family of Portuguese extraction, with second-cousin parents, in which 2 daughters had 45,X-46,XY-47,XYY mosaicism and a son had 46,XY-47,XYY mosaicism. ... In Kuwait, Alfi et al. (1980) found that Down syndrome was about 4 times more frequent among the children of closely related parents than among those with unrelated parents (p less than 0.005). By contrast, Devoto et al. (1985) could find no increased consanguinity in the parents or grandparents of Down syndrome cases. Juberg et al. (1990) reported X-chromosome mosaicism in females of 3 generations.
Amelogenesis imperfecta (AI) (amelogenesis - enamel formation; imperfecta - imperfect) is a disorder that affects the structure and appearance of the enamel of the teeth . This condition causes teeth to be unusually small, discolored, pitted or grooved, and prone to rapid wear and breakage with early tooth decay and loss. These dental problems, which vary among affected individuals, can affect both primary (baby) teeth and permanent teeth. People with this disease my also have problems involving the tissues surrounding teeth (periodontal tissues) such as gums, cementum, ligaments, and alveolar bones in which the tooth root rests. Teeth are also sensitive to either hot or cold exposures, and sometimes both.
A number sign (#) is used with this entry because of evidence that amelogenesis imperfecta type IF (AI1F) is caused by homozygous mutation in the ameloblastin gene (AMBN; 601259) on chromosome 4q13. Description Amelogenesis imperfecta type IF is characterized by hypoplastic enamel of the primary and secondary dentition. The teeth may appear rough and discolored, and the tooth enamel may be absent, pitted, or of varying thickness (Poulter et al. (2014)). Clinical Features Poulter et al. (2014) described a consanguineous Costa Rican family with generalized hypoplastic amelogenesis imperfecta involving the primary and secondary dentitions. Clinical examination of the 3 affected sisters revealed enamel that was hard, but discolored and rough.
The patient was also noted to have Nance-Horan syndrome (302350). The patient's mother reported that her former husband and his brother had 'yellow teeth,' but neither man was available for examination.
A number sign (#) is used with this entry because of evidence that hypocalcified amelogenesis imperfecta type IIIA (AI3A) is caused by heterozygous mutation in the FAM83H gene (611927) on chromosome 8q24. Description Hypocalcified amelogenesis imperfecta is characterized by enamel of normal thickness on newly erupted and unerupted and unresolved teeth. The enamel is soft and may be lost soon after eruption leaving the crown composed only of dentin. The enamel has a cheesy consistency and can be scraped from the dentin. An anterior open bite has been recorded in over 60% of the cases observed.
For a description of hypoplastic/hypomaturation amelogenesis imperfecta, see 301200. Mapping See 301200 for description of findings in a family suggesting that one form of amelogenesis imperfecta is determined by a mutation in a gene in the Xq22-q28 region (Aldred et al., 1992). This gene may be another reflection of homeology of portions of the 2 arms of the X chromosome resulting from an ancient duplication. INHERITANCE - X-linked HEAD & NECK Teeth - Amelogenesis imperfecta, hypoplastic ▲ Close
A number sign (#) is used with this entry because of evidence that amelogenesis imperfecta type IA (AI1A) is caused by heterozygous mutation in the beta-3 laminin gene (LAMB3; 150310) on chromosome 1q32. Description Hypoplastic amelogenesis imperfecta IA is characterized by enamel that may not develop to normal thickness. The enamel may have pits on the labial or buccal surfaces that are often arranged in rows and columns (see Witkop, 1989). Clinical Features Kim et al. (2013) described 2 unrelated families of Turkish and Iranian descent, respectively, with autosomal dominant hypoplastic amelogenesis imperfecta. The proband in Family 1 was a 6.5-year-old girl who presented with sensitive teeth.
The dental findings were apparently identical to those of trichodentoosseous syndrome (TDO; 190320), from which it differed only by the lack of changes in the hair and bones. ... Seow (1993) suggested that true taurodontism, as indicated by a change in the mandibular first permanent molar, occurs only in TDO syndrome and that this feature can be used to differentiate clearly between TDO and AI.
Amelogenesis imperfecta (AI) exists in isolation or associated with other abnormalities as part of a syndrome. Etiology In families with an X-linked form, it has been shown that the disorder may result from mutations in the amelogenin gene, AMELX .
A number sign (#) is used with this entry because amelogenesis imperfecta type IB (AI1B) is caused by heterozygous mutation in the enamelin gene (ENAM; 606585) on chromosome 4q13. Clinical Features Weinmann et al. (1945) made the useful division of enamel defects into 2 classes: (1) hereditary enamel hypoplasia, in which the enamel is hard but deficient in quantity, and (2) hereditary enamel hypocalcification, in which the enamel is soft and undercalcified but normal in quantity and histology (see 130900). In autosomal dominant local hypoplastic amelogenesis imperfecta, the hypoplastic defect is a horizontal row of pits, linear depressions, or one large hypoplastic area in the enamel with hypocalcification of the enamel adjacent to and below the hypoplastic area. These defects appear most prominent on the buccal surfaces of the teeth involving the middle third of the enamel. The incisal edge or occlusal surface is usually not involved (Witkop, 1957; Witkop and Sauk, 1976).
A number sign (#) is used with this entry because autosomal recessive local hypoplastic amelogenesis imperfecta (AI1C) is caused by homozygous mutation in the enamelin gene (ENAM; 606585) on chromosome 4q13. Clinical Features In the course of an extensive survey, Chosack et al. (1979) found several families with autosomal recessive local hypoplastic amelogenesis imperfecta. Characteristics included horizontal pitting and grooving more pronounced in the middle third of the crowns of most teeth of both dentitions. In a study of 50 patients with amelogenesis imperfecta, Rowley et al. (1982) found that anterior open-bite malocclusion occurred in 24%, and was always associated with a severe discrepancy in the vertical relationship of the jaws. Vertical dysgnathia also occurred in a further 20% of the patients who did not have anterior open-bite malocclusion.
PMID 8213674 . ^ a b c d e f g h i j Sur A, Sardar SK, Paria A (April 2013). "Caudal duplication syndrome" . Journal of Clinical Neonatology . 2 (2): 101–2. doi : 10.4103/2249-4847.116412 . ... (December 2016). "Caudal Duplication Syndrome: the Vital Role of a Multidisciplinary Approach and Staged Correction" . ... "A Rare Presentation of Caudal Duplication Syndrome in an Adult with No Functional Impairment" . ... PMID 1407428 . ^ a b c d Hu T, Browning T, Bishop K (March 2016). "Caudal duplication syndrome: imaging evaluation of a rare entity in an adult patient" . ... "Caudal duplication syndrome" (PDF) . Journal of the College of Physicians and Surgeons--Pakistan . 24 (1): 64–6.
Clinical Features Dominguez et al. (1993) used the term caudal duplication syndrome to describe the occurrence of duplications of different organs in the caudal region.
Radial longitudinal deficiency is frequently (67%) associated with other congenital anomalies or syndromes, including chromosomal anomalies (trisomy 13, 18 and 21), Holt-Oram syndrome, Roberts syndrome, Rothmund-Thomson syndrome, thrombocytopenia-absent radius (TAR) syndrome, Townes-Brocks syndrome, VACTERL association and Fanconi anemia.
A rare, autosomal recessive, multiple congenital anomalies/dysmorphic syndrome characterized mainly by developmental delay, variable intellectual disability, microcephaly, cerebellar hypoplasia, dysmorphic features (central incisors macrodontia and slender fingers), short stature and variable congenital anomalies. ... Clinical description The clinical features of the syndrome include developmental delay and intellectual disability. ... Differential diagnosis The disorder is distinguished from other intellectual disability syndromes mainly by short stature and progressive microcephaly.
A number sign (#) is used with this entry because of evidence that cerebellofaciodental syndrome (CFDS) is caused by homozygous or compound heterozygous mutation in the BRF1 gene (604902) on chromosome 14q32. Description Cerebellofaciodental syndrome is an autosomal recessive neurodevelopmental disorder characterized by delayed development, intellectual disability, abnormal facial and dental findings, and cerebellar hypoplasia (summary by Borck et al., 2015). ... Molecular Genetics In 6 patients from 3 unrelated families with cerebellofaciodental syndrome, Borck et al. (2015) identified homozygous or compound heterozygous mutations in the BRF1 gene (604902.0001-604902.0004).
A number sign (#) is used with this entry because of evidence that mitochondrial DNA depletion syndrome-14 (MTDPS14) is caused by homozygous mutation in the OPA1 gene (605290) on chromosome 3q29. ... Compound heterozygous mutations in the OPA1 gene can also cause Behr syndrome (BEHRS; 210000), which shows less severe, but overlapping features. For a discussion of genetic heterogeneity of autosomal recessive mtDNA depletion syndromes, see MTDPS1 (603041). Clinical Features Spiegel et al. (2016) reported 2 sisters, born of consanguineous Arab parents, with a severe lethal infantile mitochondrial encephalomyopathy and hypertrophic cardiomyopathy.
An acanthoma is a small, reddish bump that usually develops on the skin of an older adult. There are several types of acanthoma, including "acantholytic", "epidermolytic", "clear cell", and "melanoacanthoma". Though most individuals have only one acanthoma, there have been rare reports of individuals who have developed many. The exact cause of acanthoma is not known; it is sometimes called a benign tumor, and sometimes described as the result of inflammation . Acanthomas are not considered dangerous and do not require treatment, but they may be removed for cosmetic reasons or to relieve any associated symptoms.
The pervasive developmental disorders were autism , Asperger syndrome , pervasive developmental disorder not otherwise specified (PDD-NOS, i.e. all autism spectrum disorders (ASD)), childhood disintegrative disorder (CDD), overactive disorder associated with mental retardation and stereotyped movements and Rett syndrome . [1] The first four of these disorders are commonly called the autism spectrum disorders; the last disorder is much rarer, and is sometimes placed in the autism spectrum and sometimes not. [2] [3] The terminology PDD and ASD is often used interchangeably and varies depending on location. ... However, an editorial published in the October 2012 issue of American Journal of Psychiatry notes that, while some doctors argue that there is insufficient evidence to support the diagnostic distinction between ASD and PDD, multiple literature reviews found that studies showing significant differences between the two disorders significantly outnumbered those that found no difference. [8] Unlike the DSM-5, the World Health Organization ’s International Classification of Diseases , 10th edition ( ICD-10 ) categorizes PDD into four distinct subtypes, each with their own diagnostic criteria. [1] The four disorders (childhood autism, atypical autism, Rett syndrome , and other childhood disintegrative disorder) are characterized by abnormalities in social interactions and communication. [1] The disorders are primarily diagnosed based on behavioral features, although the presence of any medical conditions are important, they are not taken into account when making a diagnosis. [ medical citation needed ] Before the release of the DSM-5, some clinicians used PDD-NOS as a "temporary" diagnosis for children under the age of five when, for whatever reason, they are reluctant to diagnose autism. ... However, some parents view the PDD label as no more than a euphemism for autism spectrum disorders, problematic because this label makes it more difficult to receive aid for early childhood intervention . [ medical citation needed ] Classification [ edit ] The pervasive developmental disorders were: [6] Pervasive developmental disorder not otherwise specified (PDD-NOS), which includes atypical autism, and is the most common (47% of autism diagnoses); [9] Typical autism , the best-known; Asperger syndrome (9% of autism diagnoses); Rett syndrome ; and Childhood disintegrative disorder (CDD). ... The grouping of disorders, including PDD-NOS, Autism, Asperger Syndrome, Rett Syndrome, and CDD, has been removed and replaced with the general term of Autism Spectrum Disorders. ... Act Early." campaign - Information for parents on early childhood development and developmental disabilities NINFS Pervasive Developmental Disorders Information Page Classification D ICD - 10 : F84 ICD - 9-CM : 299 MeSH : D002659 DiseasesDB : 33524 External resources eMedicine : ped/1780 v t e Pervasive developmental disorders and autism spectrum Main Causes Comorbid conditions Epidemiology Heritability Societal and cultural aspects Medical model Therapies Diagnoses Autism spectrum ( High-functioning autism Classic autism Asperger syndrome Pervasive developmental disorder not otherwise specified Childhood disintegrative disorder Rett syndrome ) Related conditions Alexithymia Attention deficit hyperactivity disorder Anxiety disorder ( obsessive–compulsive disorder ) Late talker Epilepsy Fragile X syndrome Hyperlexia Savant syndrome Sensory processing disorder Intellectual disability Developmental coordination disorder Multiple complex developmental disorder Controversies Autism rights movement Autistic enterocolitis Facilitated communication MMR vaccine Rapid prompting method Thiomersal ( Chelation ) Diagnostic scales Gilliam Asperger's disorder scale Autism Diagnostic Observation Schedule Autism Diagnostic Interview Autism-spectrum quotient Childhood Autism Rating Scale Lists Autism-related topics Fictional characters Schools v t e Mental and behavioral disorders Adult personality and behavior Gender dysphoria Ego-dystonic sexual orientation Paraphilia Fetishism Voyeurism Sexual maturation disorder Sexual relationship disorder Other Factitious disorder Munchausen syndrome Intermittent explosive disorder Dermatillomania Kleptomania Pyromania Trichotillomania Personality disorder Childhood and learning Emotional and behavioral ADHD Conduct disorder ODD Emotional and behavioral disorders Separation anxiety disorder Movement disorders Stereotypic Social functioning DAD RAD Selective mutism Speech Stuttering Cluttering Tic disorder Tourette syndrome Intellectual disability X-linked intellectual disability Lujan–Fryns syndrome Psychological development ( developmental disabilities ) Pervasive Specific Mood (affective) Bipolar Bipolar I Bipolar II Bipolar NOS Cyclothymia Depression Atypical depression Dysthymia Major depressive disorder Melancholic depression Seasonal affective disorder Mania Neurological and symptomatic Autism spectrum Autism Asperger syndrome High-functioning autism PDD-NOS Savant syndrome Dementia AIDS dementia complex Alzheimer's disease Creutzfeldt–Jakob disease Frontotemporal dementia Huntington's disease Mild cognitive impairment Parkinson's disease Pick's disease Sundowning Vascular dementia Wandering Other Delirium Organic brain syndrome Post-concussion syndrome Neurotic , stress -related and somatoform Adjustment Adjustment disorder with depressed mood Anxiety Phobia Agoraphobia Social anxiety Social phobia Anthropophobia Specific social phobia Specific phobia Claustrophobia Other Generalized anxiety disorder OCD Panic attack Panic disorder Stress Acute stress reaction PTSD Dissociative Depersonalization disorder Dissociative identity disorder Fugue state Psychogenic amnesia Somatic symptom Body dysmorphic disorder Conversion disorder Ganser syndrome Globus pharyngis Psychogenic non-epileptic seizures False pregnancy Hypochondriasis Mass psychogenic illness Nosophobia Psychogenic pain Somatization disorder Physiological and physical behavior Eating Anorexia nervosa Bulimia nervosa Rumination syndrome Other specified feeding or eating disorder Nonorganic sleep Hypersomnia Insomnia Parasomnia Night terror Nightmare REM sleep behavior disorder Postnatal Postpartum depression Postpartum psychosis Sexual dysfunction Arousal Erectile dysfunction Female sexual arousal disorder Desire Hypersexuality Hypoactive sexual desire disorder Orgasm Anorgasmia Delayed ejaculation Premature ejaculation Sexual anhedonia Pain Nonorganic dyspareunia Nonorganic vaginismus Psychoactive substances, substance abuse and substance-related Drug overdose Intoxication Physical dependence Rebound effect Stimulant psychosis Substance dependence Withdrawal Schizophrenia , schizotypal and delusional Delusional Delusional disorder Folie à deux Psychosis and schizophrenia-like Brief reactive psychosis Schizoaffective disorder Schizophreniform disorder Schizophrenia Childhood schizophrenia Disorganized (hebephrenic) schizophrenia Paranoid schizophrenia Pseudoneurotic schizophrenia Simple-type schizophrenia Other Catatonia Symptoms and uncategorized Impulse control disorder Klüver–Bucy syndrome Psychomotor agitation Stereotypy Authority control NDL : 01207835
Most cases of benign lymphoepithelial lesions appear in conjunction with Sjögren's syndrome. When Sjögren's syndrome is present, the swelling is usually bilateral . ... If it was secondary to another disease, such as tuberculosis , sarcoidosis , lymphoma , and Sjögren's syndrome, the term used was Mikulicz's syndrome . ... - "Mikulicz's disease" ^ synd/2088 at Who Named It? - "Mikulicz's syndrome" ^ Ihrler S, Harrison J (2005). "Mikulicz's disease and Mikulicz's syndrome: analysis of the original case report of 1892 in the light of current knowledge identifies a MALT lymphoma" . ... "Mikulicz's disease and Sjögren's syndrome" . Investigative Ophthalmology & Visual Science . 41 (7): 1666–73.
IgG4-related dacryoadenitis and sialoadenitis was previously considered a subtype of Sjogren syndrome , but it is now known to be a distinct condition.
IgG4-related dacryoadenitis and sialoadenitis (Mikulicz disease) is an IgG4-related sclerosing disease (see this term) characterized by persistent, usually painless, bilateral enlargement of the lacrimal, parotid, and submandibular glands associated with elevated levels of serum immunoglobulin (Ig) G4 and with lymphocyte and IgG4-positive plasmacyte infiltration. It predominantly causes mouth and eye dryness but can also affect other organs such as the lungs, liver, and kidneys, and be accompanied by complications such as autoimmune pancreatitis (AIP), retroperitoneal fibrosis, and tubulointerstitial nephritis (see these terms).
A number sign (#) is used with this entry because of evidence that Webb-Dattani syndrome (WEDAS) is caused by homozygous mutation in the ARNT2 gene (606036) on chromosome 15q25. One such family has been reported. Description Webb-Dattani syndrome is an autosomal recessive disorder characterized by frontotemporal hypoplasia, globally delayed development, and pituitary and hypothalamic insufficiency due to hypoplastic development of these brain regions. ... Clinical Features Webb et al. (2013) reported 6 children from a highly consanguineous Saudi Arabian kindred with a congenital brain malformation syndrome and other abnormalities. Features that became apparent in the first month of life included hypernatremia due to diabetes insipidus, central hypothyroidism due to thyroid-stimulating hormone deficiency, growth failure due to growth hormone deficiency, and adrenocorticotropic deficiency. ... Inheritance The transmission pattern of Webb-Dattani syndrome in the family reported by Webb et al. (2013) was consistent with autosomal recessive inheritance. Molecular Genetics In 6 children, born of consanguineous Saudi Arabian parents, with Webb-Dattani syndrome, Webb et al. (2013) identified a homozygous truncating mutation in the ARNT2 gene (606036.0001).
Not to be confused with Carney complex or Carney-Stratakis syndrome . Carney triad ( CT ) is characterized by the coexistence of three types of neoplasms , mainly in young women, [1] including gastric gastrointestinal stromal tumor, pulmonary chondroma , and extra- adrenal paraganglioma . [2] The underlying genetic defect remains elusive. CT is distinct from Carney complex , and the Carney-Stratakis syndrome. Contents 1 Background 2 Taxonomy 2.1 Carney complex 2.2 Carney–Stratakis syndrome 3 References Background [ edit ] Carney triad (CT), named for J Aidan Carney , is considered to be a specific type of multiple endocrine neoplasia (MEN). ... Carney complex [ edit ] The Carney complex is a distinct entity, [6] characterized by myxomatous neoplasms (cardiac, endocrine, cutaneous and neural), and a host of pigmented lesions of the skin and mucosae, including the rarely occurring epitheloid blue nevus . [7] [8] Carney–Stratakis syndrome [ edit ] A third condition, the Carney–Stratakis syndrome (CSS), describes the dyad of hereditary gastrointestinal stromal tumor (GIST) and paraganglioma , that is caused by germline mutations in the mitochondrial tumor suppressor gene pathway involving the succinate dehydrogenase subunits SDHD , SDHC and SDHB . [3] References [ edit ] ^ a b OMIM - Online Mendelian Inheritance in Man. ... The triad of paragangliomas, gastric stromal tumours and pulmonary chondromas (Carney triad), and the dyad of paragangliomas and gastric stromal sarcomas (Carney-Stratakis syndrome): molecular genetics and clinical implications. ... "Separate occurrence of extra-adrenal paraganglioma and gastrointestinal stromal tumor in monozygotic twins: probable familial Carney syndrome." Pediatr Dev Pathol . 2004;7(4):380-4. ^ Diment J, Tamborini E, Casali P, Gronchi A, Carney JA, Colecchia M.
Carney et al. (1977) reported the association of gastric (epithelioid) leiomyosarcoma, functioning extraadrenal paraganglioma, and pulmonary chondroma in 2 patients and the association of 2 of the 3 tumors in 5 other patients. All were unrelated young women. One patient also had a nonfunctioning adrenocortical adenoma (Margulies and Sheps, 1988). The tumor pattern, namely multifocal lesions in multiple organs in young patients, suggested an inherited disorder, but such was not found. Carney (1983) reviewed findings in 24 affected patients (including 2 males), 6 of whom had the 3 tumors. The gastric neoplasm had metastasized in 8 patients, demonstrating its malignant nature.
A rare non-hereditary condition characterized by gastrointestinal stromal tumors (GIST, intramural mesenchymal tumors of the gastrointestinal tract with neuronal or neural crest cell origin), pulmonary chondromas and extraadrenal paragangliomas. Epidemiology Less than 100 cases have been reported worldwide. Carney's triad primarily affects young women (mean age of onset 20 years). Clinical description Most patients initially present with two of the three tumors (incomplete Carney's triad). The main symptoms at presentation are gastrointestinal bleeding, epigastric pain, anemia and palpable abdominal mass. These symptoms are related to the GIST, which occur in 99% of cases. Additional features include headaches, fatigue, anorexia, hypertension and tachycardia.
A number sign (#) is used with this entry because of evidence that autosomal dominant craniodiaphyseal dysplasia (CDD) is caused by heterozygous mutation in the SOST gene (605740) on chromosome 17q21. Sclerosteosis (SOST1; 269500) and van Buchem disease (VBCH; 239100), are allelic disorders that are less severe and show autosomal recessive inheritance. Description Craniodiaphyseal dysplasia is a severe bone dysplasia characterized by massive generalized hyperostosis and sclerosis, especially involving the skull and facial bones. Progressive bony encroachment upon cranial foramina leads to severe neurologic impairment in childhood (summary by Brueton and Winter, 1990). The sclerosis is so severe that the resulting facial distortion is referred to as 'leontiasis ossea' (leonine facies), and the bone deposition results in progressive stenosis of craniofacial foramina (summary by Kim et al., 2011).
Craniodiaphyseal dysplasia is a rare sclerotic bone disorder with a variable phenotypic expression with massive generalized hyperostosis and sclerosis, particularly of the skull and facial bones, that may lead to severe deformity.
Clinical Features Cranial and facial hyperostosis results in a characteristic clinical and radiographic appearance. The diaphyses of the bones are generally expanded. Halliday (1949) and Stransky et al. (1962) reported isolated cases with similar findings. Facial and cranial thickening and distortion are particularly striking in this form. Most cases have been mentally retarded. Unlike the situation in the craniometaphyseal dysplasias (e.g., 218400), the long bones do not show metaphyseal flaring but show diaphyseal endostosis and are shaped like a policeman's nightstick. Joseph et al. (1958), who first suggested the designation of progressive craniodiaphyseal dysplasia, described a patient with a picture they considered identical to that described by Halliday (1949).