Clinical Features Calvo et al. (2010) reported a patient with mitochondrial complex I deficiency nuclear type 19 manifesting as Leigh syndrome (see 256000). The patient had congenital lactic acidosis, athetoid movements of the limbs in early childhood, hypotonia, and cerebellar atrophy. ... Molecular Genetics In a patient with Leigh syndrome due to mitochondrial complex I deficiency nuclear type 19, Calvo et al. (2010) identified compound heterozygosity for 2 mutations in the FOXRED1 gene (Q232X, 613622.0001 and N430S, 613622.0002). ... INHERITANCE - Autosomal recessive HEAD & NECK Head - Microcephaly, acquired Eyes - Cortical blindness (1 patient) - Optic atrophy (1 patient) CARDIOVASCULAR Heart - Hypertrophic cardiomyopathy (1 patient) RESPIRATORY - Respiratory insufficiency ABDOMEN Gastrointestinal - Feeding difficulties SKELETAL Spine - Scoliosis MUSCLE, SOFT TISSUES - Hypotonia - Ragged red fibers seen on muscle biopsy NEUROLOGIC Central Nervous System - Delayed psychomotor development - Poor speech - Abnormal gait - Athetoid movements - Rigidity - Abnormal movements - Myoclonus - Poor voluntary movements - Loss of motor skills - Inability to walk - Seizures - White matter abnormalities consistent with Leigh syndrome seen on brain imaging - Cerebellar atrophy - Delayed myelination - Enlarged ventricles METABOLIC FEATURES - Lactic acidosis - Hypoglycemia LABORATORY ABNORMALITIES - Increased serum and CSF lactate - Mitochondrial respiratory complex I deficiency in various tissues MISCELLANEOUS - Onset in infancy - Two unrelated patients have been reported (last curated January 2019) MOLECULAR BASIS - Caused by mutation in the FAD-dependent oxidoreductase domain-containing protein 1 gene (FOXRED1, 613622.0001 ) ▲ Close
Drug-induced autoimmune hemolytic anemia is a type of autoimmune hemolytic anemia (AIHA; see this term) that occurs as a reaction to therapeutic drugs, and can be due to various mechanisms. Epidemiology Drug-induced AIHA is rare; annual incidence is estimated at about 1/1,000,000. It is more common in adults and is very rare in children, although some fatal cases in children have been reported. Clinical description The disease presents with anemia linked to hemolysis, and physical examination may show an enlarged spleen. Etiology To date about 100 drugs have been implicated in drug-induced AIHA, including: cephalosporins (primarily cefotetan and ceftriaxone), levodopa, methyldopa, penicillin and its derivatives, quinidine and some nonsteroidal anti-inflammatory drugs.
Asamoah (2007) argued that this patient did not have Gollop-Wolfgang complex but a multiple congenital anomaly syndrome secondary to the 8q chromosomal deletion (8q11-q13).
During a large-scale survey of persons with Usher syndrome (retinitis pigmentosa and sensorineural deafness), Beighton et al. (1993) identified 14 children in 9 Afrikaner families in South Africa with a combination of progressive rod-cone dystrophy, sensorineural deafness, and renal dysfunction of the Fanconi type leading to rickets-like skeletal changes and renal failure. ... Onset of auditory and visual dysfunction was usually before age 5 and invariably before age 10 years. Retinitis pigmentosa or Usher syndrome had initially been diagnosed in every child, and cataracts had been documented as a complicating factor in 4 of the children.
Clinical Features The 2 Amish sibs first reported by Beighton (1970) were thought to be heterozygous for the Weill-Marchesani syndrome. Both were short of stature and had long coarse hair involving the lower third of the upper arm and the upper third of the forearm bilaterally. ... In approximately three-quarters of the cases, hypertrichosis cubiti was isolated or associated with short stature only, whereas the remaining cases involved short stature as well as other features such as facial dysmorphism, limb anomalies, and psychomotor retardation or speech delay (see Wiedemann-Steiner syndrome, 605130). Inheritance Di Lernia et al. (1996) described affected father and son, suggesting autosomal dominant inheritance.
Hypertrichosis cubiti is a rare hair anomaly characterized by symmetrical, congenital or early-onset, bilateral hypertrychosis localized on the externsor surfaces of the upper extremities (especially the elbows). Short stature, or other abnormalities, such as developmental delay, facial anomalies and intellectual disability, may or may not be associated.
Clinical description Localized lipohypertrophy involves small body areas, manifesting as either a soft bump or a depression in the soft tissue, and are not usually accompanied by a metabolic syndrome. They are most frequently observed in association with repeated mechanical microtraumatism (pressure induced localized lipoatrophy) such as drug injection, but may also be seen as the sequelae of an inflammation (panniculitis-induced localized lipodystrophy). ... In addition certain medications can induce localized lipodystrophy such as steroids or antiretroviral treatment, or it can be triggered by panniculitis (such as nodular non-suppurative panniculitis, Weber-Christian syndrome). The etiology for idiopathic localized lipodystrophy and centrifugal localized lipodystrophy remains unknown.
The condition may also be present in individuals in substance withdrawal, specifically opioid withdrawal syndrome, where it is usually associated with nausea and/or vomiting. The term osmophobia comes from the Greek ὀσμή - osmē , meaning "smell, odour" [1] and φόβος - phobos , "fear". [2] Olfactophobia comes from the Latin olfacto , "to smell at". [3] See also [ edit ] List of phobias Olfactory Reference Syndrome References [ edit ] ^ ὀσμή , Henry George Liddell, Robert Scott, A Greek-English Lexicon , on Perseus ^ φόβος , Henry George Liddell, Robert Scott, A Greek-English Lexicon , on Perseus ^ olfacto , Charlton T.
In the opinion of one medical author it "may have been widely unrecognized in veteran populations, and its symptoms misattributed to other causes." [1] Symptoms include, but are not limited to, limbic encephalopathy and neurotoxic vestibulopathy . [2] Contents 1 Symptoms 1.1 Very high probability 1.2 Moderate probability 1.3 Prodromal 2 References Symptoms [ edit ] This neuropsychiatric syndrome is defined by several symptoms that distinguish it from others: [2] Very high probability [ edit ] delirium confusion disorientation Moderate probability [ edit ] dementia amnesia seizures Prodromal [ edit ] anxiety depression sleep disturbance abnormal dreams dizziness vertigo paresthesias References [ edit ] ^ Nevin, Remington L. (2019). ... ISBN 978-3-030-05383-3 . ^ a b Nevin, Remington L.; Leoutsakos, Jeannie-Marie (2017). "Identification of a Syndrome Class of Neuropsychiatric Adverse Reactions to Mefloquine from Latent Class Modeling of FDA Adverse Event Reporting System Data" .
Beare et al. (1966) described an Irish family in which 4 persons in 3 generations suffered from annular erythema. Inheritance - Autosomal dominant Skin - Annular erythema ▲ Close
In 4 generations of a family, Hall et al. (1975) observed a syndrome of small mouth and jaw with limited jaw movement disappearing by adulthood but with horizontal depression above the chin; mild microcephaly; ears missing the antihelix; and severe flexion contractures of the hands and feet, leading to subluxation of the fingers and clubfeet in the most severely affected child. ... This disorder shows phenotypic overlap with trismus-pseudocamptodactyly syndrome (158300). Head - Mild microcephaly Inheritance - Autosomal dominant Mouth - Small mouth - Small jaw - Limited jaw movement - Horizontal depression above the chin Limbs - Severe flexion contractures of hands and feet - Subluxation of fingers - Clubfeet Ears - Antihelix absent ▲ Close
Some cases of gastroschisis may resolve in utero, with closure of the hole of the abdominal wall, resulting in strangulation and destruction of the herniated bowel (vanishing gastroschisis or vanishing gut syndrome), and very short-bowel syndrome.
Omphalocele is a feature of many genetic syndromes. Nearly half of individuals with omphalocele have a condition caused by an extra copy of one of the chromosomes in each of their cells (trisomy). Up to one-third of people born with omphalocele have a genetic condition called Beckwith-Wiedemann syndrome. Affected individuals may have additional signs and symptoms associated with these genetic conditions. ... After birth, these intestinal malformations can lead to problems with digestive function, further loss of intestinal tissue, and a condition called short bowel syndrome that occurs when areas of the small intestine are missing, causing dehydration and poor absorption of nutrients.
Mastroiacovo et al. (2007) analyzed 3,322 cases of gastroschisis from 24 birth defect registries worldwide and found that 469 (14.1%) cases were registered as 'nonisolated,' including 41 chromosomal syndromes, 24 other syndromes, and 404 multiple congenital anomalies (MCA).
A rare abdominal wall malformation characterized by the bowel protruding from the fetal abdomen on the right lateral base of the umbilical cord, and without a covering sac. Epidemiology In Europe, the average recorded prevalence of gastroschisis is 1/6,000 births with an increasing trend. Clinical description The disorder occurs around the tenth week of gestation, and results in bowel protruding, without a covering sac. If the defect is large enough, other viscera (stomach, bladder and gonads) might be exteriorized in some cases by the end of gestation. The liver always remains intra-abdominal. Intestinal damage, bowel atresia and even bowel perforation may occur as a result from the primary defect.
Winter et al. (1989) raised the possibility that acromicric dysplasia (102370) may be the same as the Moore-Federman syndrome. They pointed out that the Moore-Federman syndrome had the distinction of being 'dropped' from the third edition of Smith's 'Recognizable Patterns of Human Malformation' (Smith, 1982) because there had been no further convincing case reports since the original description.
While it may be viewed as an extension of a continuous trait of pulp chamber size, it occurs also in syndromes, especially those having an ectodermal defect, e.g., trichodentoosseous syndrome (190320) and otodental dysplasia (166750).
Taurodontism is a disorder of tooth development and occurs most commonly in permanent molar teeth. It refers to an elongation of the pulp chamber of the tooth, which can cause the tooth to lie deep in the jaw ( aveolar process ). At this time the cause of taurodontism is unknown.
Taurodontism is found in association with amelogenesis imperfecta , ectodermal dysplasia and tricho-dento-osseous syndrome . The term means "bull like" teeth derived from similarity of these teeth to those of ungulate or cud-chewing animals. According to Mangion taurodontism may be: A retrograde character A primitive pattern Mendelian recessive character Atavistic feature A mutation It has also been reported in Klinefelter syndrome , XXYY and Down syndrome . The teeth involved are invariably molars, sometimes single and at the other times multiple teeth may be involved.
Early myoclonic encephalopathy [1] Specialty Neurology Early myoclonic encephalopathy ( EME ) is an epilepsy syndrome where myoclonic seizures develop in the neonatal period. After several months, the seizure pattern may develop to infantile spasms (West syndrome). Various genetic and metabolic disorders are responsible.
A number sign (#) is used with this entry because of evidence that early infantile epileptic encephalopathy-41 (EIEE41) is caused by heterozygous mutation in the SLC1A2 gene (600300) on chromosome 11p13. For a general phenotypic description and a discussion of genetic heterogeneity of EIEE, see EIEE1 (308350). Clinical Features The EPI4K Consortium (2016) reported 2 unrelated girls with EIEE41. They had an extremely severe phenotype, with onset of multiple seizure types in the first week of life followed by profound developmental impairment without detectable regression. One of the patients was a 17-year-old girl with quadriparesis, nephrocalcinosis, delayed dentition, severe growth failure with microcephaly, hirsutism, kyphoscoliosis, joint contractures, and tapering fingers.
The disorder progressed, and he was given a diagnosis of West syndrome at age 6 months. The seizures progressively decreased without use of medication until age 5 years, but recurred at 7 years.
A rare disorder characterized clinically by the onset of fragmentary myoclonus appearing in the first month of life, often associated with erratic focal seizures and a suppression-burst EEG pattern. Epidemiology The prevalence is unknown but Early myoclonic encephalopathy is a rare disease with only around 30 cases described so far. Clinical description Onset sometimes occurs as early as a few hours after birth, and postnatal movements are sometimes reported by the mother to be of the same type as those felt at the end of pregnancy. Other types of seizures, including partial seizures, massive myoclonia, and tonic spasms can also occur; usually at around 3-4 months of age. Neurological abnormalities are constant: very severe delay in psychomotor acquisitions, marked hypotonia, and disturbed alertness, sometimes with a vegetative state.
A number sign (#) is used with this entry because of evidence that early infantile epileptic encephalopathy-30 (EIEE30) is caused by heterozygous mutation in the SIK1 gene (605705) on chromosome 21q22. For a general phenotypic description and a discussion of genetic heterogeneity of EIEE, see 308350. Clinical Features Hansen et al. (2015) reported 6 unrelated children with a severe neurodevelopmental disorder associated with early-onset refractory epilepsy. Seizure onset occurred shortly after birth or within the first months of life and included myoclonic, generalized tonic-clonic, and atonic seizures, as well as infantile spasms. All patients had severely delayed psychomotor development. Two patients died in infancy, and the 4 who survived showed severe cognitive impairment with poor or absent speech and autistic features.
ANKRD26 -related thrombocytopenia is characterized by lifelong mild-to-moderate thrombocytopenia with a normal platelet size and no syndromic associations. Most individuals have normal hemostasis or a mild bleeding phenotype and do not develop severe spontaneous bleeding. ... The risk for myeloid malignancies (including myelodysplastic syndrome, acute myelogenous leukemia, and chronic myelogenous leukemia) is increased in individuals with ANKRD26 pathogenic variants. ... Clinical Characteristics Clinical Description Individuals with ANKRD26 -related thrombocytopenia usually present with lifelong mild-to-moderate thrombocytopenia with a normal platelet size and no syndromic associations. Incidental presentation following routine complete blood count is not uncommon. Some individuals are identified after developing a myeloid neoplasm such as acute myeloid leukemia or myelodysplastic syndrome. Bleeding history. Most individuals have normal hemostasis or a mild bleeding phenotype and do not develop severe spontaneous bleeding. ... This is best accomplished at a large academic institution with experience in the management of individuals with germline predisposition syndromes [Babushok et al 2016]. Surveillance Surveillance for early detection of myeloid neoplasms is indicated in all individuals with ANKRD26 -related thrombocytopenia.
Some patients also exhibit features of Ehler-Danlos syndrome (EDS; see 130000), with hyperextensible skin and joint hypermobility, whereas others have stiffening of joints from early childhood (Kyndt et al., 2007; Ritelli et al., 2017; Mercer et al., 2017). ... Histologically, changes in the mitral valve of 1 case resembled those seen in the 'floppy valve syndrome' (Read et al., 1965) or in Marfan syndrome (which was suggested by no other feature of the cases). Di Ferrante et al. (1975) reported 2 Italian maternal cousins with congenital heart disease, 'floppy valve syndrome,' hernias, short stature, stretchable skin, and moderate joint hypermobility, which the authors considered to represent an X-linked form of Ehlers-Danlos syndrome (EDS5; see HISTORY). ... The authors stated that it was not clear whether the skeletal findings were coincidental in this family or part of an inherited syndrome with EA. Newbury-Ecob et al. (1993) described a British family in which 2 brothers and the son of a daughter of one of them had valvular dysplasia. ... History Beighton (1968) described 2 families in which X-linked inheritance of Ehlers-Danlos syndrome, designated EDS5, was probable.
X-linked cardiac valvular dysplasia is a condition characterized by the abnormal development (dysplasia) of heart (cardiac) valves. The normal heart has four valves, two on the left side of the heart and two on the right side, that allow blood to move through the heart and prevent blood from flowing backward. In X-linked cardiac valvular dysplasia, one or more of the four heart valves is thickened and cannot open and close completely when the heart beats and pumps blood. These malformed valves can cause abnormal blood flow and an irregular heart sound during a heartbeat (heart murmur). The signs and symptoms of X-linked cardiac valvular dysplasia vary greatly among affected individuals.
A rare genetic cardiac malformation characterized by progressive myxomatous degeneration predominantly of the mitral valve (but not uncommonly with multivalvular involvement), presenting as valve thickening and dysfunction with variable stenosis, prolapse, and/or regurgitation, and potentially resulting in lethal heart failure. Hyperextensible skin and joint hypermobility have been reported in some patients. Hemizygous males display a more severe phenotype than heterozygous females.
Heart valve dysplasia Specialty Cardiology Heart valve dysplasia is a congenital heart defect which affects the aortic, pulmonary, mitral, and tricuspid heart valves . Dysplasia of the mitral and tricuspid valves can cause leakage of blood or stenosis . Dysplasia of the mitral and tricuspid valves - also known as the atrioventricular (AV) valves - can appear as thickened, shortened, or notched valves. The chordae tendinae can be fused or thickened. The papillary muscles can be enlarged or atrophied . The cause is unknown, but genetics play a large role. Dogs and cats with tricuspid valve dysplasia often also have an open foramen ovale , an atrial septal defect , or inflammation of the right atrial epicardium . [1] In dogs, tricuspid valve dysplasia can be similar to Ebstein's anomaly in humans. [2] Mitral valve stenosis is one of the most common congenital heart defects in cats.