Hirschsprung disease-nail hypoplasia-dysmorphism syndrome is a fatal malformative disorder that is characterized by Hirschsprung disease, hypoplastic nails, distal limb hypoplasia and minor craniofacial dysmorphic features (flat facies, upward slanting palpebral fissures, narrow philtrum, narrow, high arched palate, micrognathia, low set ears with abnormal helices).
Clinical Features In a male and female sib pair of Sikh origin and a male offspring of first-cousin Pakistani Muslims, Al-Gazali et al. (1988) described a combination of Hirschsprung disease (megacolon), hypoplastic nails, and minor dysmorphic facial features. In 1 male infant, bilateral hydronephrosis was detected on routine ultrasound in midtrimester, and imperforate anus was noted at birth. Vesicostomy was performed for an obstructed bladder thought to be the result of posterior urethral valves. A left inguinal hernia was repaired during surgery for Hirschsprung disease. All 3 patients died as infants. GU - Hydronephrosis Inheritance - Autosomal recessive Nails - Hypoplastic nails Abdomen - Inguinal hernia HEENT - Minor dysmorphic facies GI - Hirschsprung megacolon - Imperforate anus ▲ Close
Lethal occipital encephalocele-skeletal dysplasia syndrome is a rare, genetic, bone development disorder characterized by occipital and parietal bone hypoplasia leading to occipital encephalocele, calvarial mineralization defects, craniosynostosis, radiohumeral fusions, oligodactyly and other skeletal anomalies (arachnodactyly, terminal phalangeal aplasia of the thumbs, bilateral absence of the great toes, pronounced bilateral angulation of femora, shortened limbs, advanced osseous maturation).
She was thought to have Antley-Bixler syndrome (see 207410), but no mutations were found in the FGFR2 (176943) or POR (124015) genes or in the FGF9 gene (600921).
A rare, genetic, syndromic intellectual disability disease characterized by severe intrauterine and post-natal growth delay, moderate to severe intellectual disability, and neonatal-onset hepatopathy with fibrosis, steatosis, and/or cholestasis, occasionally leading to liver failure.
A number sign (#) is used with this entry because of evidence that growth retardation, impaired intellectual development, hypotonia, and hepatopathy (GRIDHH) is caused by compound heterozygous mutation in the IARS gene (IARS1; 600709) on chromosome 9q22. Description GRIDHH is an autosomal recessive multisystem disorder characterized by poor overall growth, impaired intellectual development, hypotonia, and variable liver dysfunction. Additional features, such as seizures and hearing loss, may also be present (summary by Kopajtich et al., 2016). Clinical Features Kopajtich et al. (2016) reported 3 unrelated patients with a similar multisystem disorder characterized by intrauterine and postnatal growth retardation, including small head circumference (-3 to -5 SD), hypotonia, and delayed psychomotor development with variable severity of impaired intellectual development. The patients were 18, 19, and 3 years old at the time of last examination.
Infant acute respiratory distress syndrome is a lung disorder that affects premature infants caused by developmental insufficiency of surfactant production and structural immaturity of the lungs.
Laurin-Sandrow syndrome (LSS) is characterised by complete polysyndactyly of the hands, mirror feet and nose anomalies (hypoplasia of the nasal alae and short columella), often associated with ulnar and/or fibular duplication (and sometimes tibial agenesis).
They proposed that the disorder be called Laurin-Sandrow syndrome. Hatchwell and Dennis (1996) reported a girl with mirror hands and feet and associated groove of the nasal columella. ... Mutation in a HOX gene was suggested by Hatchwell and Dennis (1996) as a likely candidate for the syndrome. Matsumoto et al. (1997) found reports of 7 patients with mirror hands and feet. ... Kantaputra (2001) described a Thai man with Laurin-Sandrow syndrome, the ninth reported case. He had an underdeveloped nasal bone, scar-like seams under the nose, large heads of the mandibular condyles, and brachymesophalangy of toes as newly observed findings of the syndrome. ... Innis and Hedera (2004) suggested that these patients had 'segmental' Laurin-Sandrow syndrome due to somatic mutation involving the precursor cells of the left upper limb. ... Father-to-son transmission of Laurin-Sandrow syndrome in the family reported by Kjaer et al. (2005) excluded X-linked inheritance.
A rare non-syndromic limb malformation characterized by a hand or foot with more than five digits that has a recognizable anterior/posterior axis of symmetry, either with a hallux- or thumb-like structure or an interdigital space in the middle.
Clinical manifestations depend on the amount of residual beta globin chains production, and are similar to sickle cell disease, including anemia, vascular occlusion and its complications, acute episodes of pain, acute chest syndrome, pulmonary hypertension, sepsis, ischemic brain injury, splenic sequestration crisis and splenomegaly.
Sickle cell beta thalassemia Other names Sickle cell-β thalassemia Specialty Hematology Sickle cell-beta thalassemia is an inherited blood disorder . The disease may range in severity from being relatively benign and like sickle cell trait to being similar to sickle cell disease . [1] [2] Contents 1 Signs and symptoms 2 Cause 2.1 Mutations 3 Diagnosis 4 Treatment 5 References 6 External links Signs and symptoms [ edit ] Patients with sickle cell-beta thalassemia may present with painful crises similar to patients with sickle cell disease Cause [ edit ] Sickle cell-beta thalassemia is caused by inheritance of a sickle cell allele from one parent and a beta thalassemia allele from the other. [3] Mutations [ edit ] A sickle allele is always the same mutation of the beta-globin gene (glutamic acid to valine at amino acid six). In contrast, beta-thalassemia alleles can be created by many different mutations including both deletion and non-deletion forms. Diagnosis [ edit ] Patient may present with symptomatic anemia or with sickle crises. In the United States and other countries with new-born screening programs, the disease may be identified in neonates. [4] Diagnostic tests include DNA sequencing , hemoglobin electrophoresis , and high-performance liquid chromatography . [5] Treatment [ edit ] Treatment is the same as for patients with sickle cell disease.
Sickle beta thalassemia is an inherited condition that affects hemoglobin, the protein in red blood cells that carries oxygen to different parts of the body. It is a type of sickle cell disease . Affected people have a different change (mutation) in each copy of their HBB gene: one that causes red blood cells to form a "sickle" or crescent shape and a second that is associated with beta thalassemia, a blood disorder that reduces the production of hemoglobin. Depending on the beta thalassemia mutation, people may have no normal hemoglobin (called sickle beta zero thalassemia) or a reduced amount of normal hemoglobin (called sickle beta plus thalassemia). The presence of sickle-shaped red blood cells, which often breakdown prematurely and can get stuck in blood vessels, combined with the reduction or absence of mature red blood cells leads to the many signs and symptoms of sickle beta thalassemia. Features, which may include anemia (low levels of red blood cells), repeated infections, and frequent episodes of pain, generally develop in early childhood and vary in severity depending on the amount of normal hemoglobin made.
Signs and symptoms may include acute episodes of pain, splenic infarction and splenic sequestration crisis, acute chest syndrome, focal segmental glomerulosclerosis, ischemic brain injury, peripheral retinopathy, and osteonecrosis.
Hemoglobin SC disease , is a type of sickle cell disease , which means it affects the shape of the red blood cells. Red blood cells contain a protein called hemoglobin , which is responsible for carrying blood throughout the body. People with hemoglobin SC disease have red blood cells that are differently shaped and therefore do not carry oxygen as effectively. Symptoms of hemoglobin SC disease include anemia and episodes of fatigue and extreme pain ( vaso-occlusive crisis ). The severity of the symptoms can vary from person to person. Hemoglobin SC disease is caused by mutations in the gene that tells our bodies how to make hemoglobin.
A rare, genetic, chromosomal anomaly syndrome resulting from a partial deletion of the long arm of chromosome 21 characterized by pre- and post-natal growth delay, short stature, intellectual disability, developmental delay with severe language impairment, thrombocytopenia, and craniofacial dysmorphism which may include microcephaly, downslanted palpebral fissures, low-set ears, broad nose, thin upper vermillion, and downturned corners of the mouth.
PCNA-related progressive neurodegenerative photosensitivity syndrome is a rare neurodegenerative disease caused by homozygous mutations in the PCNA gene and characterized by neurodegeneration, postnatal growth retardation, prelingual sensorineural hearing loss, premature aging, ocular and cutaneous telangiectasia, learning difficulties, photophobia, and photosensitivity with evidence of predisposition to sun-induced malignancy.
Description Ataxia-telangiectasia-like disorder-2 is an autosomal recessive syndrome resulting from defects in DNA excision repair. ... Clinical Features Baple et al. (2014) reported 4 patients between 11 and 31 years of age from an extended Ohio Amish family with a neurodegenerative syndrome. The main features included delayed development or learning difficulties, prelingual sensorineural hearing loss, progressive gait instability and ataxia, progressive muscle weakness, dysarthria, dysphagia, and cognitive decline with age. ... The features were reminiscent of syndromes caused by DNA repair defects, such as xeroderma pigmentosum (see, e.g., XPA; 278700), Cockayne syndrome (see, e.g., CSA; 216400), and ataxia-telangiectasia (AT; 208900).
Temple syndrome is a rare, genetic disease characterized by pre-and postnatal growth delay, feeding difficulties, muscular hypotonia, motor developmental delay (with or without mild intellectual disability) and mild facial dysmorphism, such as broad, prominent forehead, short nose with flat nasal root and wide tip, downturned corners of mouth, high-arched palate and micrognathia.
A number sign (#) is used with this entry because Temple syndrome is an imprinting disorder involving genes within the imprinted region of chromosome 14q32. Description Temple syndrome is a short stature disorder of imprinting. ... Ioannides et al. (2014) reviewed 51 published cases of Temple syndrome associated with maternal uniparental disomy of chromosome 14 (40 cases), paternal deletions on chromosome 14 (5 cases), or loss of methylation at the intergenic differentially methylated region (IG-DMR; 6 cases). ... Nomenclature Buiting et al. (2008) suggested the designation 'Temple syndrome' for this disorder because 'Temple was the first to describe a patient with UPD(14)mat and a patient with a DLK1/GTL2 epimutation (Temple et al. (1991, 2007)).'
Maternal uniparental disomy of chromosome 14 is a rare chromosomal anomaly characterized by prenatal and postnatal growth retardation, hypotonia, motor delay, early puberty, obesity, short adult stature, small hands and feet, mild intellectual disability, and mild dysmorphic facial features (frontal bossing, short nose with wide nasal tip, micrognathia, high palate, short philtrum).
A rare, genetic, syndromic intellectual disability characterized by mild to severe intellectual disability associated with variable features, including hypotonia, dyskinesia, spasticity, wide-based gait, microcephaly, epilepsy and behavioral problems.
A number sign (#) is used with this entry because of evidence that X-linked mental retardation-102 (MRX102) is caused by mutation in the DDX3X gene (300160) on Xp11. Clinical Features Snijders Blok et al. (2015) reported 38 females with mild to severe intellectual disability and variable neurologic features, including hypotonia in 12 (76%), movement disorders comprising dyskinesia, spasticity, and stiff-legged or wide-based gait in 17 (45%), microcephaly in 12 (32%), behavioral problems such as autism spectrum disorder, hyperactivity, and aggression in 20 (53%), and epilepsy in 6 (16%). Additional variable nonneurologic features included joint hyperlaxity, skin pigmentary abnormalities, cleft lip and/or palate, hearing and visual impairment, and precocious puberty. Some patients had abnormal brain imaging findings, such as corpus callosum hypoplasia (35%), ventricular enlargement (35%), and evidence of cortical dysplasia (4 patients). Although common dysmorphic facial features were noted, there was no consistent recognizable phenotype.
A rare genetic multiple congenital anomalies syndrome characterized by global developmental delay and intellectual disability with limited or absent speech development, microcephaly, cardiac anomalies, and dysmorphic facial features, predominantly broad nasal tip and thin, tented upper lip.
Tham et al. (2015) reported 6 children 10 years of age or younger, including a set of monozygotic twins, from 5 unrelated families with intellectual disability and distinct syndromic features. All patients were delivered by emergency cesarean section and 4 had severe neonatal respiratory distress.
Verloes et al. (1990) described a 'new' form of dwarfing skeletal dysplasia associated with major ocular abnormalities in a father and son. Although the small bones of the limbs were almost unaffected, thickening of the diaphyses of the long bones was striking on initial radiographs. With age, metaphyseal deformation became more prominent. The epiphyses became irregular and their growth was delayed, particularly at the femoral heads. The femoral neck showed an unusual 'lip' on the inner edge. In adulthood, only enlarged metaphyses and deformed femoral necks persisted. The vertebrae showed moderate deformation with irregular flattening, and narrowing of the spinal canal with a reduced interpedicular distance.
A rare genetic multiple congenital anomalies/dysmorphic syndrome characterized by variable developmental delay and intellectual disability, movement disorder or gait abnormalities, and dysmorphic craniofacial features (such as facial asymmetry, broad forehead, posteriorly rotated ears, thick lower lip, micrognathia, or cleft palate).
The diagnosis of Gabriele-de Vries syndrome is established in a proband by the identification of a heterozygous pathogenic variant involving YY1 or a heterozygous deletion of 14q32.2 involving only YY1 . ... Genetic counseling. Gabriele-de Vries syndrome is inherited in an autosomal dominant manner. All probands reported to date with Gabriele-de Vries syndrome whose parents have undergone molecular genetic testing have the disorder as a result of a de novo YY1 pathogenic variant or deletion. ... Diagnosis No formal clinical diagnostic criteria exist for Gabriele-de Vries syndrome. Suggestive Findings The clinical spectrum of Gabriele-de Vries syndrome is variable. Gabriele-de Vries syndrome should be considered in individuals presenting with the following clinical findings.
A number sign (#) is used with this entry because of evidence that Gabriele-de Vries syndrome (GADEVS) is caused by heterozygous mutation in the YY1 gene (600013) on chromosome 14q32. Description Gabriele-de Vries syndrome is an autosomal dominant neurodevelopmental disorder characterized by delayed psychomotor development, variable cognitive impairment, often with behavioral problems, feeding problems, some movement abnormalities, and dysmorphic facial features. ... Molecular Genetics In 10 unrelated patients with Gabriele-de Vries syndrome, Gabriele et al. (2017) identified 10 different de novo heterozygous missense or truncating mutations in the YY1 gene (see, e.g., 600013.0001-600013.0005).
Distal 17p13.3 microdeletion syndrome is a rare partial monosomy of the short arm of chromosome 17 with a variable phenotype characterized by prenatal and postnatal growth retardation, developmental delay, mild intellectual disability, macrocephaly, mild facial dysmorphisms including prominent forehead, hypertelorism, thick upper and/or lower lip vermillion, and structural abnormalities of the brain variably including white matter abnormalities, prominent Virchow-Robin spaces, Chiari I malformation, corpus callosum hypoplasia, but no lissencephaly.
Ferro-cerebro-cutaneous syndrome is a rare, genetic, metabolic liver disease characterized by progressive neurodegeneration, cutaneous abnormalities, including varying degrees of ichthyosis or seborrheic dermatitis, and systemic iron overload.
A rare systemic disease for which two subtypes exist, either related to the gene PLOD1 or FKBP22 , and for which the clinically overlapping characteristics include congenital muscle hypotonia, congenital or early-onset kyphoscoliosis (progressive or non-progressive), and generalized joint hypermobility with dislocations/subluxations (in particular of the shoulders, hips, and knees). Additional features which may occur in both subtypes are skin hyperextensibility, easy bruising of the skin, rupture/aneurysm of a medium-sized artery, osteopenia/osteoporosis, blue sclerae, umbilical or inguinal hernia, chest deformity, marfanoid habitus, talipes equinovarus, and refractive errors. Gene-specific features, with variable presentation, are additionally observed in each subtype.
A rare subtype of kyphoscoliotic Ehlers-Danlos syndrome characterized by congenital muscle hypotonia, congenital or early-onset kyphoscoliosis (progressive or non-progressive), and generalized joint hypermobility with dislocations/subluxations (in particular of the shoulders, hips, and knees).
Genetic Heterogeneity of Ehlers-Danlos Syndrome, Kyphoscoliotic Type See EDSSKCL2 (614557), caused by mutation in the FKBP14 gene (614505). Classification of Ehlers-Danlos Syndromes The current classification of Ehlers-Danlos syndromes is based on a 2017 international classification described by Malfait et al. (2017), which recognizes 13 EDS subtypes. ... Beighton et al. (1998) reported on a revised nosology of the Ehlers-Danlos syndromes, designated the Villefranche classification. ... Although the authors considered their cases to be an autosomal recessive variant of Sotos syndrome (117550), Cohen (1989) proposed that these patients had a separate entity, which they called the Nevo syndrome. ... Because the clinical features in patients reported with Nevo syndrome were similar to those of EDS VIA, Giunta et al. (2005) studied 7 patients diagnosed with Nevo syndrome, 2 of whom had been reported by Al-Gazali et al. (1997) and 1 by Hilderink and Brunner (1995), and identified homozygous mutations in the PLOD1 gene in all (see 153454.0001 and 153454.0006).
A number sign (#) is used with this entry because of evidence that Ehlers-Danlos syndrome arthrochalasia type 1 (EDSARTH1) is caused by heterozygous mutation in the COL1A1 (120150) on chromosome 17q21. ... Genetic Heterogeneity of Arthrochalasia-type Ehlers-Danlos Syndrome See EDSARTH2 (617821), caused by mutation in the COL1A2 gene (120160).
A form of Ehlers-Danlos syndrome (EDS) characterized by congenital bilateral hip dislocation, severe generalized joint hypermobility with recurrent joint dislocations and subluxations, hyperextensible and/or fragile skin. ... Clinical description Patients affected by arthrochalasia Ehlers-Danlos syndrome (aEDS) present at birth with severe hypermobility of both small and large joints with easy dislocation on manipulation, in combination with muscular hypotonia. ... Differential diagnosis Differential diagnosis includes Larsen syndrome, classical EDS (cEDS), dermatosparaxis EDS (dEDS), kyphoscoliotic EDS (kEDS) and musculocontractural EDS (mcEDS), Loeys-Dietz syndrome and autosomal recessive cutis laxa type 2B.
A number sign (#) is used with this entry because Ehlers-Danlos syndrome arthrochalasia type 2 (EDSARTH2) is caused by heterozygous mutation in the COL1A2 (120160) gene on chromosome 7q21. ... Nicholls et al. (1991) reported a 29-year-old male with bilateral hip dislocation at birth and with other features of the Ehlers-Danlos syndrome type VIIB. The patient's affected daughter was born with bilateral hip dislocation, joint hyperflexibility, feet in the equinovarus position, and hyperextensible skin. ... The history of frequent fractures found in this family was slightly atypical for type VIIB Ehlers-Danlos syndrome and suggested a phenotypic overlap with osteogenesis imperfecta. ... Molecular Genetics From studies of type I collagen in a patient with Ehlers-Danlos syndrome type VIIB (EDSARTH2), Eyre et al. (1985) determined that 1 allele of the COL1A2 gene carried a de novo mutation (120160.0001) that resulted in deletion of 15 to 20 residues in the junction domain that spans the N-propeptidase cleavage site and the N-telopeptide cross-linking sequence.