Since some motility of cilia was retained (as is true in dynein-defective cilia), the authors suggested ciliary dyskinesia as a designation alternative to 'immotile cilia syndrome.' See CILD1 (244400). Respiratory - Chronic sinopulmonary disease Lab - Transposition of ciliary number 1 doublet microtubule Inheritance - Autosomal recessive ▲ Close
Pachygyria may occur alone (isolated) or as part of various underlying syndromes. Symptoms vary among affected people and may include moderate to severe developmental delay, seizures, poor muscle tone and control, feeding or swallowing difficulties, and small head size (microcephaly).
Grade 2 is observed in children with Miller–Dieker syndrome (a combination of lissencephaly with dysmorphic facial features, visceral abnormalities, and polydactyly). ... Another common treatment is a gastrostomy (insertion of a feeding tube) to reduce possible poor nutrition and repeated aspiration pneumonia. [4] Microcephalic osteodysplastic primordial dwarfism [ edit ] Microcephalic osteodysplastic primordial dwarfism ( MOPD ) type II is an autosomal multisystem disorder including severe pre- and post-natal growth retardation, microcephaly with Seckel syndrome -like facial appearance, and distinctive skeletal alterations. ... PMID 12668601 . ^ a b Pieh C, Goebel HH, Engle EC, Gottlob I (2003). "Congenital fibrosis syndrome associated with central nervous system abnormalities". ... External links [ edit ] Classification D ICD - 10 : Q04.3 MeSH : D054082 Online Mendelian Inheritance in Man (OMIM): 600176 v t e Congenital malformations and deformations of nervous system Brain Neural tube defect Anencephaly Acephaly Acrania Acalvaria Iniencephaly Encephalocele Chiari malformation Other Microcephaly Congenital hydrocephalus Dandy–Walker syndrome other reduction deformities Holoprosencephaly Lissencephaly Microlissencephaly Pachygyria Hydranencephaly Septo-optic dysplasia Megalencephaly Hemimegalencephaly CNS cyst Porencephaly Schizencephaly Polymicrogyria Bilateral frontoparietal polymicrogyria Spinal cord Neural tube defect Spina bifida Rachischisis Other Currarino syndrome Diastomatomyelia Syringomyelia
Peterson and Schimke (1968) observed cup-shaped ears in members of 5 generations with at least 4 instances of male-to-male transmission. Their proband had Pierre Robin syndrome (261800). The embryology of the auricle and a large amount of clinical material on various anomalies of the auricle were presented by Rogers (1968).
Sclerotic fibroma Specialty Dermatology Sclerotic fibromas [1] are a cutaneous condition characterized by well-circumscribed, dome-shaped, dermal hypocellular nodules composed predominantly of sclerotic thick collagen bundles. [2] See also [ edit ] Blepharochalasis List of cutaneous conditions List of cutaneous neoplasms associated with systemic syndromes References [ edit ] ^ http://dermatlas.med.jhmi.edu/derm/result.cfm?
A rare acute myeloid leukemia (AML) characterized by the presence of acute leukemia with at least 20% peripheral blood or bone marrow blasts with morphological features of myelodysplasia, or occurrence in patients with a prior history of a myelodysplastic syndrome (MDS) or myelodysplastic/myeloproliferative neoplasm, with MDS-related cytogenetic abnormalities, in the absence of specific genetic abnormalities characteristic of AML with recurrent genetic abnormalities.
Motzkin et al. (1992) and Tarnok et al. (2003) reported Blount disease in Bardet-Biedl syndrome (209900). Skel - Osteochondrosis deformans tibiae - Bowlegs - Tibia vara Inheritance - Autosomal recessive vs. multifactorial ▲ Close
Blount disease is a growth disorder of the shin bone ( tibia ) characterized by inward turning of the lower leg (bowing) that slowly worsens over time. While it is not uncommon for young children to have bowed legs , typically the bowing improves with age. There are two types of Blount disease (early-onset and late-onset), based on whether symptoms begin before or after four years of age. Blount disease may occur in one or both legs and can lead to shortening of the affected leg and other changes within bones of the legs. The cause of Blount disease is not well understood; however, a variety of hereditary and genetic factors are likely involved.
Description Blount disease is a developmental condition characterized by disordered endochondral ossification of the medial part of the proximal tibial physis resulting in multiplanar deformities of the lower limb (review by Sabharwal, 2009). Clinical Features Blount (1937) described 22 cases of bowlegs in infants, with progressive deformity and radiologic findings of sloping proximal tibial epiphysis and a medial beak of the metaphysis. Blount (1937) suggested the existence of an infantile type with onset in the first year or two of life and an adolescent type developing just before puberty (see 259200). Bathfield and Beighton (1978) noted a predilection for blacks. Duncan et al. (1983) reviewed the literature emphasizing the higher frequency in blacks than in whites, the higher frequency of the infantile form than the adolescent form, and the higher frequency of bilateral involvement than unilateral involvement. Inheritance Blount disease is probably a multifactorial disorder with genetic, humoral, biomechanical, and environmental factors (Sabharwal, 2009).
Blount disease is characterized by disturbed growth of the inner portion of the upper tibial extremity, progressively leading to bowlegged deformity with bone angulation just below the knee (tibia varus). In 60% of cases, the condition affects both legs. Epidemiology Prevalence is unknown. Clinical description Clinically, patients with Blount disease present with bowing and length discrepancy in the lower limbs and a medial prominence of the proximal tibia. Obesity and early walking are predisposing factors for the development of the disorder. Etiology The underlying causes are controversial: it seems to be a multifactorial disease, but the contribution of genetic factors is unknown.
Distal trisomy 2p is a rare chromosomal anomaly syndrome, resulting from the partial duplication of the short arm of chromosome 2, with a highly variable phenotype principally characterized by pre- and post-natal growth failure, global developmental delay, facial dysmorphism (incl. high forehead/frontal bossing, abnormal ear shape and/or position, hypertelorism/telecanthus, broad/depressed nasal bridge) and ocular anomalies (e.g. exophthalmos, retinal hypopigmentation, optic nerve and foveal hypoplasia).
Dextrocardia with situs inversus can also be associated with primary ciliary dyskinesia (also known as Kartagener syndrome ). Treatment typically depends on the heart or physical problems the person may have in addition to dextrocardia with situs inversus.
Spondyloepimetaphyseal dysplasia, Missouri type is characterized by moderate-to-severe metaphyseal changes, mild epiphyseal involvement, rhizomelic shortening of the lower limbs with bowing of the femora and/or tibiae, coxa vara, genu varum and pear-shaped vertebrae in childhood. Epidemiology The syndrome has been described in a large Missouri (US) kindred with 14 affected members in 4 generations.
A number sign (#) is used with this entry because of evidence that the Missouri type of spondyloepimetaphyseal dysplasia (SEMD) is caused by mutation in the MMP13 gene (600108). A form of metaphyseal anadysplasia (MANDP1) with autosomal dominant inheritance is also caused by mutation in the MMP13 gene. Also see MANDP2 (613073), an autosomal recessive form of metaphyseal anadysplasia, caused by mutation in the MMP9 gene (120361). Clinical Features Spondyloepimetaphyseal Dysplasia, Missouri Type Patel et al. (1993) described a large Missouri kindred with a novel form of SEMD characterized by moderate to severe metaphyseal changes; mild epiphyseal involvement; pear-shaped vertebrae in childhood; rhizomelic shortening, especially of the lower limbs; and genu varum deformities secondary to bowing of the femurs, tibias, or both. The modeling defects improved spontaneously by early adolescence, but the affected individuals remained shorter than their age-matched unaffected sibs.
The sister showed no symptoms but a lack of glycogen was identified through muscle biopsy. The syndrome is caused by homozygous missense mutations in the gene encoding muscle glycogen synthase.
A number sign (#) is used with this entry because of evidence that muscle glycogen storage disease-0 (GSD0B) is caused by homozygous mutation in the GYS1 gene (138570), which encodes muscle glycogen synthase, on chromosome 19q13. Clinical Features Among the offspring of consanguineous parents of Syrian origin, Kollberg et al. (2007) described cardiomyopathy and exercise intolerance associated with complete absence of muscle glycogen. The oldest brother developed normally until the age of 4 years, when he had an episode of tonic-clonic seizures. At the age of 10.5 years, while playing outside his school, he suddenly collapsed as the result of cardiac arrest. At autopsy, the heart weighed 200 g (normal range, 139 to 178). The left ventricular wall was thickened.
Epidemiology So far, around 20 cases have been reported in the literature. The syndrome affects both males and females and onset occurs in infancy or early childhood.
Hypomyelination with atrophy of basal ganglia and cerebellum (H-ABC) is a disease that affects certain parts of the brain. Symptoms usually begin in infancy or early childhood and worsen over time. Severity of symptoms and rate of progression can vary. Symptoms may include delayed motor development, learning difficulties, upper-motor neuron dysfunction (spasticity, exaggerated reflexes, and Babinski signs ), dystonia, rigidity, involuntary movements, and speech and swallowing problems. H-ABC is caused by a mutation in the TUBB4A gene. Inheritance is autosomal dominant, but most cases are due to a new mutation occurring for the first time in a person with the condition. Treatment may involve taking medications to ease symptoms, physical therapy, and surgery when dystonia does not improve with medication.
TUBB4A -related leukodystrophy is a disorder that affects the nervous system. Leukodystrophies are conditions that involve abnormalities of the nervous system's white matter, which consists of nerve fibers covered by a fatty substance called myelin. Myelin insulates nerve fibers and promotes the rapid transmission of nerve impulses. In particular, TUBB4A -related leukodystrophy involves hypomyelination, which means that the nervous system has a reduced ability to form myelin. In some affected individuals, myelin may also break down, which is known as demyelination.
A number sign (#) is used with this entry because hypomyelinating leukodystrophy-6 (HLD6) is caused by heterozygous mutation in the TUBB4A gene (602662) on chromosome 19p13. Mutation in the TUBB4A gene can also cause dystonia-4 (DYT4; 128101). Description Hypomyelinating leukodystrophy-6, also known as hypomyelinating leukodystrophy with atrophy of the basal ganglia and cerebellum, is a neurologic disorder characterized by onset in infancy or early childhood of delayed motor development and gait instability, followed by extrapyramidal movement disorders, such as dystonia, choreoathetosis, rigidity, opisthotonus, and oculogyric crises, progressive spastic tetraplegia, ataxia, and, more rarely, seizures. Most patients have cognitive decline and speech delay, but some can function normally. Brain MRI shows a combination of hypomyelination, cerebellar atrophy, and atrophy or disappearance of the putamen.
Peripheral hypothyroidism may also be caused by defects in thyroid hormone transport, such as in Allan-Herndon-Dudley syndrome (see this term) where X-linked peripheral hypothyroidism is associated with mental retardation and neurologic abnormalities including quadriplegia.
Mapping Berg et al. (1968) concluded that the Hunter syndrome locus (309900) and the Xm locus are within measurable distance of each other, the best estimate of the recombination fraction being 0.09.
They have fewer extra renal manifestations (e.g. involvement of lung, eye, ear, nose and throat), fewer constitutional symptoms (e.g. fever, weight loss, muscle pain and arthralgia) and a high prevalence of nephrotic syndrome and chronic renal lesions. Their prognosis is generally poorer.
Ossification occurs with calcification of the ear cartilages in hereditary conditions such as diastrophic dysplasia (222600), cold sensitivity (120100), alkaptonuria (203500), and Keutel syndrome (245150). DiBartolomeo (1985) gave a full review of what he called 'the petrified auricle.'
A number sign (#) is used with this entry because of evidence that Amish lethal microcephaly, also known as thiamine metabolism dysfunction syndrome-3 (THMD3), is caused by homozygous mutation in the SLC25A19 gene (606521) on chromosome 17q25. Thiamine metabolism dysfunction syndrome-4 (THMD4; 613710) is an allelic disorder with a milder phenotype.
Differential Diagnosis Microcephaly has a wide variety of causative factors. It can be syndromic or isolated, environmental or genetic, congenital or acquired [Battaglia & Carey 2003]. ... The degree of microcephaly is much greater in Amish lethal microcephaly than in any of these other genetically defined microcephaly syndromes. Additionally, 2-ketoglutaric aciduria has not been reported as a finding with these disorders. ... Among other genetic malformation syndromes, a similar level of urinary 2-ketoglutarate is also characteristic of the autosomal recessive form of DOORS ( d eafness, o nychodystrophy, o steodystrophy, intellectual disability [formerly known as mental r etardation] s eizures) syndrome, associated with biallelic pathogenic variants in TBC1D24 (see TBC1D24 -Related Disorders).
Amish lethal microcephaly is a disorder in which infants are born with a very small head and underdeveloped brain. Infants with Amish lethal microcephaly have a sloping forehead and an extremely small head size. They may also have an unusually small lower jaw and chin (micrognathia) and an enlarged liver (hepatomegaly). Affected infants may have seizures and difficulty maintaining their body temperature. Often they become very irritable starting in the second or third month of life.
Microcephalic primordial dwarfism due to RTTN deficiency is a rare, genetic, multiple congenital anomalies/dysmorphic syndrome characterized by primary microcephaly, profound short stature, moderate to severe intellectual disability, global developmental delay, craniofacial dysmorphism (e.g. sloping forehead, high and broad nasal bridge) and variable brain malformations, including simplified gyration, pachygyria, polymicrogyria, reduced sulcation, dysgenesis of corpus callosum and deformed ventricles.
A number sign (#) is used with this entry because of evidence that microcephaly, short stature, and polymicrogyria with or without seizures (MSSP) is caused by homozygous or compound heterozygous mutation in the RTTN gene (610436) on chromosome 18q22. Clinical Features Kheradmand Kia et al. (2012) reported a consanguineous Turkish family in which 2 sibs were demonstrated to have diffuse asymmetric polymicrogyria extending from the frontal to the temporal, parietal, and occipital lobes on brain MRI. Other imaging findings included mild ventricular enlargement and thin or short corpus callosum. One patient had mild cerebellar atrophy. The patients were 12 and 14 years old at the time of the report. Both had microcephaly, moderate to severe mental retardation, poor speech, dysarthria, and seizures.
Several cases have been associated with cardiomyopathy, dropped head syndrome and respiratory involvement. Muscle biopsy can reveal inflammatory changes.
"Late-onset rod myopathy (a new syndrome?): light and electron microscopic observations in two cases". ... "Sporadic late-onset nemaline myopathy in a patient with primary Sjögren's syndrome". Journal of Neurology . 259 (2): 358–60. doi : 10.1007/s00415-011-6160-4 .
Esophageal duplication cyst is a rare, congenital, non-syndromic esophageal malformation, most frequently located in the distal esophagus and usually diagnosed in childhood, characterized by tubular or spherical cystic masses that have a double layer of surrounding smooth muscle lined with squamous or enteric epithelium, are continuous or contiguous to the esophagus and may, or may not, communicate with the esophageal lumen.