answer:What are the signs and symptoms of Opitz G/BBB syndrome? Opitz G/BBB syndrome mainly affects structures along the midline of the body. The most common features of the condition are wide-spaced eyes (hypertelorism); defects of the larynx, trachea, and/or esophagus causing breathing problems and difficulty swallowing (dysphagia); and in males, the urethra opening on the underside of the penis (hypospadias). Mild intellectual disability and developmental delay occur in about 50 percent of people with Opitz G/BBB syndrome. Delays in motor skills, speech delays, and learning difficulties may also occur. Some individuals with Opitz G/BBB syndrome have features similar to autistic spectrum disorders, including impaired communication and socialization skills. About half of affected individuals also have cleft lip with or without a cleft palate. Some have cleft palate alone. Heart defects, an obstruction of the anal opening (imperforate anus), and brain defects such as an absence of the tissue connecting the left and right halves of the brain (agenesis of the corpus callosum) occur in less than 50 percent of those affected. Facial abnormalities that may be seen in this disorder can include a flat nasal bridge, thin upper lip, and low set ears. These features vary among affected individuals, even within the same family. The signs and symptoms of the autosomal dominant form of the condition are comparable to those seen in the X-linked form. However, the X-linked form of Opitz G/BBB syndrome tends to include cleft lip with or without cleft palate, while cleft palate alone is more common in the autosomal dominant form. Females with X-linked Opitz G/BBB syndrome are usually mildly affected, as hypertelorism may be the only sign of the disorder. The Human Phenotype Ontology provides the following list of signs and symptoms for Opitz G/BBB syndrome. If the information is available, the table below includes how often the symptom is seen in people with this condition. You can use the MedlinePlus Medical Dictionary to look up the definitions for these medical terms. Signs and Symptoms Approximate number of patients (when available) Abnormality of the pharynx 90% Anteverted nares 90% Displacement of the external urethral meatus 90% Epicanthus 90% Abnormality of the voice 50% Cognitive impairment 50% Respiratory insufficiency 50% Increased number of teeth 7.5% Low-set, posteriorly rotated ears 7.5% Pectus carinatum 7.5% Pectus excavatum 7.5% Prominent metopic ridge 7.5% Reduced number of teeth 7.5% Sensorineural hearing impairment 7.5% Craniosynostosis 5% Abnormality of cardiovascular system morphology - Abnormality of the kidney - Abnormality of the nasopharynx - Abnormality of the ureter - Absent gallbladder - Agenesis of corpus callosum - Anal atresia - Anal stenosis - Aplasia/Hypoplasia of the cerebellar vermis - Aspiration - Atria septal defect - Autosomal dominant inheritance - Bifid scrotum - Bifid uvula - Cavum septum pellucidum - Cerebellar vermis hypoplasia - Cerebral cortical atrophy - Cleft palate - Cleft upper lip - Coarctation of aorta - Conductive hearing impairment - Cranial asymmetry - Cryptorchidism - Depressed nasal bridge - Diastasis recti - Dysphagia - Frontal bossing - Gastroesophageal reflux - Hiatus hernia - High palate - Hypertelorism - Hypospadias - Inguinal hernia - Intellectual disability - Laryngeal cleft - Muscular hypotonia - Patent ductus arteriosus - Posterior pharyngeal cleft - Posteriorly rotated ears - Prominent forehead - Pulmonary hypertension - Pulmonary hypoplasia - Short lingual frenulum - Smooth philtrum - Strabismus - Telecanthus - Tracheoesophageal fistula - Umbilical hernia - Ventricular septal defect - Ventriculomegaly - Weak cry - Wide nasal bridge - Widow's peak - X-linked recessive inheritance - The Human Phenotype Ontology (HPO) has collected information on how often a sign or symptom occurs in a condition. Much of this information comes from Orphanet, a European rare disease database. The frequency of a sign or symptom is usually listed as a rough estimate of the percentage of patients who have that feature. The frequency may also be listed as a fraction. The first number of the fraction is how many people had the symptom, and the second number is the total number of people who were examined in one study. For example, a frequency of 25/25 means that in a study of 25 people all patients were found to have that symptom. Because these frequencies are based on a specific study, the fractions may be different if another group of patients are examined. Sometimes, no information on frequency is available. In these cases, the sign or symptom may be rare or common.

answer:What causes Opitz G/BBB syndrome? The X-linked form of Opitz G/BBB syndrome is caused by mutations in the MID1 gene. The MID1 gene provides instructions for making a specific protein called midline-1. This protein helps regulate the function of microtubules, which are rigid, hollow fibers that make up the cell's structural framework (the cytoskeleton). Microtubules help cells maintain their shape, assist in the process of cell division, and are essential for the movement of cells (cell migration). The MID1 gene is a member of a group of genes called the TRIM (tripartite motif) family. The proteins produced from this large family of genes are involved in many cellular activities. Primarily, TRIM proteins play a role in the cell machinery that breaks down (degrades) unwanted proteins. As part of its protein degrading function, midline-1 is responsible for recycling certain proteins, including phosphatase 2A (PP2A), integrin alpha-4 (ITGA4), and serine/threonine-protein kinase 36 (STK36). The recycling of these three proteins so they can be reused instead of broken down is essential because they are needed for normal cellular functioning. Mutations in the MID1 gene lead to a decrease in midline-1 function, which prevents this protein recycling. As a result, certain proteins are not recycled, and they accumulate in cells. This buildup impairs microtubule function, resulting in problems with cell division and migration. Researchers speculate that the altered midline-1 protein affects how the cells divide and migrate along the midline of the body during development, resulting in the features of Opitz G/BBB syndrome. Some people who have a family history of X-linked Opitz G/BBB syndrome have no detectable MID1 mutation. The reason for this is not yet known, although some researchers have suggested the involvement of other unknown genes. The autosomal dominant form of Opitz G/BBB syndrome is caused by a deletion of a small piece of chromosome 22, specifically 22q11.2, which is why researchers consider this condition to be part of 22q11.2 deletion syndrome. It is not yet known which deleted gene(s) within this region of chromosome 22 specifically cause the signs and symptoms of Opitz G/BBB syndrome. In others with autosomal dominant Opitz G/BBB syndrome, the cause is related to a mutation in the SPECCIL gene. Click on the gene name to learn more about its role in the development of this condition.

answer:How is Opitz G/BBB syndrome inherited? Opitz G/BBB syndrome often has an X-linked pattern of inheritance. A condition is considered X-linked if the mutated gene that causes the disorder is located on the X chromosome, one of the two sex chromosomes (the other sex chromosome is the Y chromosome). In most cases, males experience more severe symptoms of the disorder than females. This is because females have two different X chromosomes in each cell, and males have one X chromosome and one Y chromosome. A characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons, because fathers only pass a Y chromosome on to their sons (which is what makes them male). In some cases, an affected person inherits a MID1 mutation from an affected parent, while in other cases, it may result from a new mutation in the affected individual. These cases occur in people with no history of the disorder in their family. A female who has the X-linked form of Opitz G/BBB syndrome has a 25% (1 in 4) chance to have a daughter with the mutation, a 25% chance to have a son with the mutation, a 25% chance to have an unaffected daughter, and a 25% chance to have an unaffected son. This also means that there is a 50% chance, with each pregnancy, for the child to inherit the mutation. A male with the X-linked dominant form of Opitz G/BBB syndrome will pass the mutation on to all of his daughters and none of his sons. Researchers have also described an autosomal dominant form of Opitz G/BBB syndrome caused by a deletion in one copy of chromosome 22 in each cell. In some cases, an affected person inherits the chromosome with a deleted segment from a parent, while in other cases, the condition results from a new deletion in the affected individual. These cases occur in people with no history of the disorder in their family. Males and females with the autosomal dominant form of Opitz G/BBB syndrome usually have the same degree of severity of symptoms. A male or female who has the autosomal dominant form of Opitz G/BBB syndrome has a 50% (1 in 2) chance with each pregnancy for the child (male or female) to inherit the genetic abnormality.

answer:How is Opitz G/BBB syndrome diagnosed? The diagnosis of Opitz G/BBB syndrome is usually based on clinical findings. In order to differentiate the X-linked form from 22q11.2 deletion syndrome (the autosomal dominant form), the pattern of inheritance within the family may be assessed. Molecular genetic testing for mutations in the MID1 gene is available for confirmation. Between 15 and 45% of males with clinically diagnosed Opitz G/BBB syndrome are found to have a mutation in this gene.