Lung agenesis - heart defect - thumb anomalies is a very rare syndrome characterized by unilateral complete or partial lung agenesis, congenital cardiac defects and ipsilateral thumb anomalies.
Jaiman et al. (2016) reported a female fetus, conceived of unrelated parents of Indian descent, with LACHT syndrome. There was intrauterine fetal demise at 36 weeks' gestation.
Schilbach-Rott syndrome (SRS) is an autosomal dominant dysmorphic disorder that is characterized by dysmorphic facies with hypotelorism, blepharophimosis, and cleft palate, and the frequent occurrence of hypospadias in males.
Description Schilbach-Rott syndrome is an autosomal dominant disorder characterized by hypotelorism, epicanthal folds, cleft palate, dysmorphic facies, and hypospadias in males. ... Becerra-Solano et al. (2007) reported a Mexican father and son with Schilbach-Rott syndrome. The 3.5-year-old son had low Apgar scores at birth along with central cleft palate, hypospadias, and inguinal hernia. ... De Carvalho et al. (2008) concluded that the disorder was most similar to that described by Schilbach and Rott (1988), which could also be referred to as the blepharofacioskeletal syndrome (BRSS). Shkalim et al. (2009) reported a Jewish family of Turkish-Libyan descent in which a father and his 2 offspring, a boy and a girl, had features most reminiscent of Schilbach-Rott syndrome. ... Shkalim et al. (2009) commented on the phenotypic similarities to holoprosencephaly (HPE; 236100), but concluded that the disorder most resembled Schilbach-Rott syndrome. Array CGH did not reveal any putative pathogenic changes, and molecular analysis excluded mutations in the SEPT9 (604061), SHH (600725), and TWIST (601622) genes.
Clinical Features Mehes (1993) described a Hungarian brother and sister, aged 4 years and 9 months and 3 years and 5 months, respectively, with delayed speech development, facial asymmetry, strabismus, and a transverse earlobe crease like that seen in Beckwith-Wiedemann syndrome (130650). The mother had the same features.
Recurrent metabolic encephalomyopathic crises-rhabdomyolysis-cardiac arrhythmia-intellectual disability syndrome is a rare, genetic, neurodegenerative disease characterized by episodic metabolic encephalomyopathic crises (of variable frequency and severity which are frequently precipitated by an acute illness) which manifest with profound muscle weakness, ataxia, seizures, cardiac arrhythmias, rhabdomyolysis with myoglobinuria, elevated plasma creatine kinase, hypoglycemia, lactic acidosis, increased acylcarnitines and a disorientated or comatose state.
TANGO2- related metabolic encephalopathy and arrhythmias is a disease that can cause episodes of metabolic crises and abnormal heart rhythms ( arrhythmia ). A metabolic crisis is caused by having low blood sugar ( hypoglycemia ) and the buildup of toxic products in the blood. A metabolic crisis can occur in any person with a metabolic disorder, and they are more likely to occur after a person has gone long periods without eating or during an illness. Most people with TANGO2 -related metabolic encephalopathy and arrhythmias present with symptoms of a breakdown of muscle tissue ( rhabdomyolysis ). This can cause kidney damage and symptoms include fatigue , muscle weakness, and having a dark color of the urine.
Cardiac involvement, with severe arrhythmias including torsade de pointes and long QT syndrome, was a consistent and potentially life-threatening condition.
A number sign (#) is used with this entry because of evidence that X-linked syndromic mental retardation-33 (MRXS33) is caused by mutation in the TAF1 gene (313650) on chromosome Xq13. Description X-linked syndromic mental retardation-33 is an X-linked recessive neurodevelopmental disorder characterized by delayed psychomotor development, intellectual disability, and characteristic facial features (summary by O'Rawe et al., 2015). Clinical Features O'Rawe et al. (2015) reported 12 boys from 9 unrelated families with a complex X-linked neurodevelopmental syndrome. The boys had global developmental delay, intellectual disability with delayed speech and language, generalized hypotonia, and joint hypermobility.
Sharony et al. (2002) described 3 sibs (2 females, 1 male), born of Arabic-Muslim consanguineous healthy parents, with an apparently 'new' lethal familial short-limb bone dysplasia associated with multiple congenital anomalies (MCA). Clinical abnormalities included short limbs and short hands, cloverleaf skull, frontal bossing, wide anterior fontanel, hypertelorism, bilateral microphthalmia, cataract, low-set ears, narrow chest, ambiguous genitalia, cardiac ventricular septal defect, and agenesis of the corpus callosum. Radiologic abnormalities included cloverleaf skull, hypoplastic clavicles and scapulas, thin and wavy cupped ribs, flat vertebral bodies with coronal clefting and several unossified vertebral pedicles, and hypoossification of the pubic bone. Long bones were short and bowed with abnormal metaphyses and unossified epiphyses. Degenerating chondrocytes with disorganization of the hypertrophied cartilage and short disorganized columns of hypertrophied areas were found.
A rare genetic multiple congenital anomalies/dysmorphic syndrome characterized by global developmental delay and moderate to severe intellectual disability, as well as variable other manifestations, such as macro- or microcephaly, epilepsy, hypotonia, behavioral problems, stereotypic movements, and facial dysmorphism (including arched eyebrows, long palpebral fissures, prominent nasal bridge, upturned nose, dysplastic ears , and broad mouth), among others.
A number sign (#) is used with this entry because of evidence that autosomal dominant mental retardation-48 (MRD48) is caused by heterozygous mutation in the RAC1 gene (602048) on chromosome 7p22. Clinical Features Reijnders et al. (2017) reported 7 unrelated boys, ranging from 4.5 months to 15 years of age, with global developmental delay and moderate to severe intellectual disability. The phenotype was highly variable: 1 patient had an IQ of 35 at age 13, several had poor or absent speech, and several had delayed or impaired walking. Other neurologic features included poor feeding, hypotonia (in 4 patients), seizures (3), behavioral problems (3), and stereotypical movements (3). Four patients had microcephaly (-2.5 to -5 SD), 1 was normocephalic, and 2 had macrocephaly (+4.16 and +4.5 SD).
The authors suggested that this association is a distinct syndrome with autosomal or X-linked dominant inheritance. The syndrome shares many manifestations with Gordon syndrome (114300), but hearing loss was not mentioned in the reported cases of Gordon syndrome.
A rare genetic multiple congenital anomalies/dysmorphic syndrome characterized by global developmental delay and intellectual disability, progressive spondyloepimetaphyseal dysplasia, short stature, short fourth metatarsals, and dysmorphic craniofacial features (including microcephaly, hypertelorism, epicanthal folds, mild ptosis, strabismus, malar hypoplasia, short nose, depressed nasal bridge, full lips, small, low-set ears, and short neck).
A number sign (#) is used with this entry because of evidence that spondyloepimetaphyseal dysplasia of the Faden-Alkuraya type (SEMDFA) is caused by homozygous mutation in the RSPRY1 gene (616585) on chromosome 16q13. Clinical Features Faden et al. (2015) studied a consanguineous Bedouin Saudi family in which 4 sibs had progressive spondyloepimetaphyseal dysplasia, short stature, facial dysmorphism, short fourth metatarsals, and intellectual disability. The proband was a 13-year-old girl with a history of delayed motor milestones in infancy, who was walking at 5 years of age but progressively lost the ability to walk and was wheelchair-bound. She could follow simple commands but expressive language was severely limited. Examination revealed poor weight gain, severe short stature, microcephaly, dysmorphic facial features, small low-set ears, and short neck.
Dyggve-Melchior-Clausen (DMC) syndrome is a rare, progressive genetic condition characterized by abnormal skeletal development, microcephaly, and intellectual disability.
Yunis et al. (1980) described a Colombian family in which 10 males in 3 generations, in a typical X-linked recessive pedigree pattern, had the Dyggve-Melchior-Clausen syndrome. The affected males varied in age from 13 to 15 years.
Clinical Features Among the children from an uncle-niece marriage in Greenland, Dyggve et al. (1962) found 3 with a condition resembling Hurler syndrome (607014) and Morquio syndrome (253000) in some respects. ... Naffah and Taleb (1974) described spinal compression from odontoid hypoplasia, as in the Morquio syndrome. The DMC gene may have a relatively high frequency in Lebanese (Naffah, 1976; Bonafede and Beighton, 1978). Schorr et al. (1977) described the DMC syndrome in 6 Moroccan Jews and 2 Arabs from Gaza, distributed in 2 families and ranging in age from 4 to 25 years. ... Analysis of 3 small, unrelated families with DMC syndrome provided evidence of linkage to the same region, a result consistent with the hypothesis that the 2 disorders are allelic. ... Independently, using a positional cloning strategy, El Ghouzzi et al. (2003) identified the DMC gene as mutant in the DMC syndrome. They detected 7 deleterious mutations, 4 of which were nonsense, 2 splice site, and 1 frameshift, among 10 affected families (see, e.g., 607461.0007-607461.0008).
Differential diagnosis Differential diagnoses include Smith-McCort syndrome, which presents with the same clinical and radiological features as DMC but without intellectual deficiency, and mucopolysaccharidosis type 4 which is clinically similar but has specific radiological and enzymatic signs.
The distal limb deficiencies-micrognathia syndrome is characterized by the combination of symmetric severe distal limb reduction deficiencies affecting all four limbs (oligodactyly), microretrognathia, and microstomia with or without cleft palate.
Spondyloepimetaphyseal dysplasia-short limb-abnormal calcification syndrome is a rare, genetic primary bone dysplasia disorder characterized by disproportionate short stature with shortening of upper and lower limbs, short and broad fingers with short hands, narrowed chest with rib abnormalities and pectus excavatum, abnormal chondral calcifications (incl. larynx, trachea and costal cartilages) and facial dysmorphism (frontal bossing, hypertelorism, prominent eyes, short flat nose, wide nostrils, high-arched palate, long philtrum).
A number sign (#) is used with this entry because of evidence that spondylometaepiphyseal dysplasia, short limb-hand type, is caused by homozygous mutation in the DDR2 gene (191311) on chromosome 1q23. Clinical Features Borochowitz et al. (1993) described 3 cases of a 'new' severe short-limb bone dysplasia, which they termed spondylometaepiphyseal dysplasia, short limb-hand type. The 3 unrelated patients were born into 2 separate Sephardic Jewish families and a Puerto Rican family. Abnormalities included small stature with short limbs and short hands, a short nose with wide nasal bridge and wide nostrils, a long philtrum, ocular hypertelorism, retro/micrognathia, and a narrow chest. Radiologic abnormalities included platyspondyly, short tubular bones with very abnormal metaphyses and epiphyses beyond early infancy, short ribs, and a typical evolution of bony changes.
Epilepsy and cognitive decline have also been described. Etiology The syndrome is caused by mutations in the DARS2 gene, which encodes mitochondrial aspartyl-tRNA synthetase.
Summary Clinical characteristics. Leukoencephalopathy with brain stem and spinal cord involvement and lactate elevation (LBSL) is characterized by slowly progressive cerebellar ataxia and spasticity with dorsal column dysfunction (decreased position and vibration sense) in most patients. The neurologic dysfunction involves the legs more than the arms. The tendon reflexes are retained. Deterioration of motor skills usually starts in childhood or adolescence, but occasionally not until adulthood. Dysarthria develops over time. Occasional findings include: epilepsy; learning problems; cognitive decline; and reduced consciousness, neurologic deterioration, and fever following minor head trauma. Many affected individuals become wheelchair dependent in their teens or twenties.
Leukoencephalopathy with brain stem and spinal cord involvement and lactate elevation (LBSL) is a rare neurological disease characterized by slowly progressive cerebellar ataxia (lack of control of the movements) and spasticity with dorsal column dysfunction (decreased position and vibration sense) in most patients. The disease involves the legs more than the arms. It usually starts in childhood or adolescence, but in some cases not until adulthood. Difficulty speaking develops over time. Other symptoms may include: epilepsy; learning problems; cognitive decline; and reduced consciousness, neurologic deterioration, and fever following minor head trauma. Many affected individuals become wheelchair dependent in their teens or twenties. The earlier the onset the more severe the disease is. The diagnosis is made in persons who had the characteristic abnormalities observed on brain and spinal cord MRI scans and with the genetic test identifiying the DARS2 gene alteration (mutation).
Leukoencephalopathy with brainstem and spinal cord involvement and lactate elevation (commonly referred to as LBSL) is a progressive disorder that affects the brain and spinal cord. Leukoencephalopathy refers to abnormalities in the white matter of the brain, which is tissue containing nerve cell fibers (axons ) that transmit nerve impulses. Most affected individuals begin to develop movement problems during childhood or adolescence. However, in some individuals, these problems do not develop until adulthood. People with LBSL have abnormal muscle stiffness (spasticity) and difficulty with coordinating movements (ataxia).
A number sign (#) is used with this entry because of evidence that leukoencephalopathy with brainstem and spinal cord involvement and lactate elevation (LBSL) can be caused by homozygous or compound heterozygous mutation in the gene encoding mitochondrial aspartyl-tRNA synthetase (DARS2; 610956) on chromosome 1q25. Description Leukoencephalopathy with brainstem and spinal cord involvement and lactate elevation (LBSL) is defined on the basis of a highly characteristic constellation of abnormalities observed by magnetic resonance imaging and spectroscopy (Scheper et al., 2007). Affected individuals develop slowly progressive cerebellar ataxia, spasticity, and dorsal column dysfunction, sometimes with a mild cognitive deficit or decline. Clinical Features A novel leukoencephalopathy with brainstem and spinal cord involvement and high lactate was described by van der Knaap et al. (2002) in 8 patients. They showed a distinct magnetic resonance spectroscopy (MRS) pattern of inhomogeneous cerebral white matter abnormalities and selective involvement of brainstem and spinal tracts.
Clinical Features In 2 Hutterite sisters, Opitz et al. (1985) reported a disorder characterized by congenital shortness with mild spondylorhizomelic dwarfism; later deceleration of weight gain presumably due to CNS-based severe feeding problems; a CNS defect with normal prenatal brain growth but later deceleration from the 50th to the 2nd centile with severe mental retardation and decorticate disturbance of neurologic function and possible renal involvement with terminal nephrotic syndrome. The older sister died at age 3 years. ... The trunk was short. GU - Terminal nephrotic syndrome Growth - Congenital shortness - Mild spondylorhizomelic dwarfism - Feeding problems Neuro - Normal prenatal brain growth - Later decelerated brain growth - Severe mental retardation - Decorticate neurological function Inheritance - Autosomal recessive ▲ Close
IRIDA (Iron-refractory iron deficiency anemia) syndrome is a rare autosomal recessive iron metabolism disorder characterized by iron deficiency anemia (hypochromic, microcytic) that is often unresponsive to oral iron intake and partially responsive to parenteral iron treatment. ... Serum ferritin levels are mostly within the normal range, or even slightly elevated after intravenous iron treatment. Etiology IRIDA syndrome is due to mutations the TMPRSS6 gene encoding Matriptase 2, a transmembrane serine protease that plays an essential role in down-regulating hepcidin, the key regulator of iron homeostasis.
A number sign (#) is used with this entry because of evidence that iron-refractory iron deficiency anemia (IRIDA) can be caused by homozygous or compound heterozygous mutation in the TMPRSS6 gene (609862) on chromosome 22q12. Variation in the TMPRSS gene has been associated with hemoglobin levels as a quantitative trait; see HCHGQ3, 613284. Description Finberg et al. (2008) referred to this phenotype as iron-refractory iron deficiency anemia (IRIDA) and reviewed the key features: a congenital hypochromic, microcytic anemia; a very low mean corpuscular erythrocyte volume; a low transferrin saturation; abnormal iron absorption characterized by no hematologic improvement following treatment with oral iron; and abnormal iron utilization characterized by a sluggish, incomplete response to parenteral iron. The authors noted that although urinary levels of hepcidin (606464) are typically undetectable in individuals with iron deficiency, in 5 individuals with IRIDA urinary hepcidin/creatinine ratios were within or above the normal range. Clinical Features Buchanan and Sheehan (1981) described 2 brothers and a sister with microcytic anemia but no evidence of reduced iron intake or blood loss.
Iron-refractory iron deficiency anemia is one of many types of anemia , which is a group of conditions characterized by a shortage of healthy red blood cells. This shortage prevents the blood from carrying an adequate supply of oxygen to the body's tissues. Iron-refractory iron deficiency anemia results from an inadequate amount (deficiency) of iron in the bloodstream. It is described as "iron-refractory" because the condition is totally resistant (refractory) to treatment with iron given orally and partially resistant to iron given in other ways, such as intravenously (by IV). In people with this form of anemia, red blood cells are abnormally small (microcytic) and pale (hypochromic).
Iron-refractory iron deficiency anemia (IRIDA) is a type of iron deficiency anemia that typically does not improve with oral iron treatment . Children with IRIDA have too little iron in their blood, which causes their red blood cells to be small (microcytic) and pale (hypochromic). The anemia tends to be mild to moderate, but without enough healthy red blood cells, different parts of the body do not get enough oxygen. Symptoms of IRIDA are usually mild, but may include pale skin and in some cases, feeling weak, tired, or dizzy. Growth and development of a child with IRIDA is usually normal. IRIDA is caused by changes or mutations in the TMPRSS6 gene and inheritance is autosomal recessive.
A type of idiopathic inflammatory myopathy characterized by evocative skin lesions and symmetrical proximal muscle weakness. Epidemiology Annual incidence is estimated between 1 to 10 new cases/million population/year, and prevalence between 1/50,000 and 1/10,000. Dermatomyositis (DM) is more common in women than in men (2:1). In the United States, a Black-to-Caucasian ratio of 3:1 has been reported. Clinical description Onset is generally in adulthood, in some cases earlier (Juvenile DM, see this term). Patients typically present a heliotrope rash (erythema of eyelids with or without edema) and Gottron's papules (lichenoid papules over knuckles and sometimes knees, elbows), violaceous erythema (on extensor surfaces and face), poikiloderma (photoexposed areas), and periungual telangiectasias.
Dermatomyositis is an autoimmune condition that causes skin changes and muscle weakness. Symptoms can include a red skin rash around the eyelids, red bumps around the joints, and muscle weakness in the arms and legs. Dermatomyositis is most common in adults between ages 40 and 60, or in children between ages 5 and 15. Muscle weakness gets worse over time and can lead to stiff joints and muscle wasting. The cause for dermatomyositis is unknown. Diagnosis is made through a clinical exam and microscopic examination of a piece of skin and muscle.
It can occur either as an isolated malformation or in association with other deformities , [1] particularly limb defects in a syndrome known as oromandibular limb hypogenesis syndrome . ... External links [ edit ] Classification D ICD - 10 : Q38.3 v t e Congenital malformations and deformations of digestive system Upper GI tract Tongue , mouth and pharynx Cleft lip and palate Van der Woude syndrome tongue Ankyloglossia Macroglossia Hypoglossia Esophagus EA/TEF Esophageal atresia: types A, B, C, and D Tracheoesophageal fistula: types B, C, D and E esophageal rings Esophageal web (upper) Schatzki ring (lower) Stomach Pyloric stenosis Hiatus hernia Lower GI tract Intestines Intestinal atresia Duodenal atresia Meckel's diverticulum Hirschsprung's disease Intestinal malrotation Dolichocolon Enteric duplication cyst Rectum / anal canal Imperforate anus Rectovestibular fistula Persistent cloaca Rectal atresia Accessory Pancreas Annular pancreas Accessory pancreas Johanson–Blizzard syndrome Pancreas divisum Bile duct Choledochal cysts Caroli disease Biliary atresia Liver Alagille syndrome Polycystic liver disease This medical sign article is a stub .