In the pattern of mendelian inheritance, X- linked dominant inheritance means that all who inherit the X chromosome will present with the condition. In the case of maternal x-linked inheritance sons and daughters have an equal chance of inheriting the condition as there is a 50% chance of inheriting the defective X chromosome from their mother as opposed to a non affected X chromosome from their father. However in paternal X-linked dominant inheritance, sons will be unaffected as they inherit a Y chromosome from their father while daughters are sure to inherit the defective X-chromosome.

Neurofibromatosis is a genetic disease caused by the mutation of the neurofibromin gene on Chromosome 17. The diagnostic criteria for Neurofibromatosis type 1 are two or more of the following:-6 or more cafe au lait macules-2 or more cutaneous neurofibroma or one plexiform Neurofibroma-Axillary of groin freckling -Optic pathway glioma -2 or more Lisch nodules (hamartomas of the iris seen on slit lamp examination)-Bony dysplasia (such as sphenoid wing dysplasia, bowing of the long bones, or pseudarthrosis)-First degree relative with neurofibromatosis type 1

Cystic fibrosis is a progressive, genetic disease. A defective gene causes a thick, sticky build-up of mucus in the lungs, pancreas, and other organs. In the lungs, the mucus clogs the airways and traps bacteria leading to infections, extensive lung damage, and eventually, respiratory failure. In the pancreas, the mucus prevents the release of digestive enzymes that allow the body to break down food and absorb vital nutrients. Since the digestive enzymes are not being made, the food is not completely digested making them bulky, smelly, and hard to flush away. Finger clubbing is a prominent feature of cystic fibrosis on most patients.

Types of DNA mutations and their impactpoint mutation:Substitution: One base is incorrectly added during replication and replaces the pair in the corresponding position on the complementary strand as in Sickle cell anaemiaInsertion: One or more extra nucleotides are inserted into replicating DNA, often resulting in a frameshift as in one form of beta-thalassemiaDeletion: One or more nucleotides is skipped during replication or otherwise excised, often resulting in a frameshift as in Cystic fibrosis.Chromosomal mutation:Inversion: One region of a chromosome is flipped and reinserted as in Opitz-Kaveggia syndromeDeletion: A region of a chromosome is lost, resulting in the absence of all the genes in that area as in Cri du chat syndromeDuplication: A region of a chromosome is repeated, resulting in an increase in dosage from the genes in that region as in some cancers and Charcot-Marie toothTranslocation: A region from one chromosome is aberrantly attached to another chromosome as in One form of leukaemiaCopy number variation:Gene amplification: The number of tandem copies of a locus is increased as in Some breast cancersExpanding trinucleotide repeat: The normal number of repeated trinucleotide sequences is expanded as in Fragile X syndrome, Huntington’s disease

Pierre Robin sequence is a condition present at birth, in which the infant has micrognathia, a tongue that is placed further back than normal (glossoptosis), and cleft palate. This combination of features can lead to difficulty breathing and problems with eating early in life. Pierre Robin sequence may occur isolated or be associated with a variety of other signs and symptoms (described as syndromic). The exact causes of Pierre Robin syndrome are unknown. The most common otic anomaly is otitis media, occurring 80% of the time, followed by auricular anomalies in 75% of cases. Hearing loss, mostly conductive, occurs in 60% of patients, while external auditory canal atresia occurs in only 5% of patients.

In the pattern of mendelian inheritance, X- linked dominant inheritance means that all who inherit the X chromosome will present with the condition. In the case of maternal x-linked inheritance, sons and daughters have an equal chance of inheriting the condition as there is a 50% chance of inheriting the defective X chromosome from their mother as opposed to a non affected X chromosome from their father. However, in paternal X-linked dominant inheritance, sons will be unaffected as they inherit a Y chromosome from their father while daughters are sure to inherit the defective X-chromosome.

Rett syndrome is a disorder that affects the brain and occurs most commonly in girls. It presents with a period of normal development followed by severe problems with language and communication, learning, coordination, and other brain functions.

Angelman Syndrome is a genetic disorder that affects the nervous system. The features of this condition include intellectual disability, a delay in developmental milestones, and movement disorders. The features occur as a result of the deletion or mutation of the maternal copy of the UBE3A gene located on Chromosome 15q. Though individuals usually inherit one copy of this gene from each parent, only the maternal gene remains active in parts of the brain. This phenomenon is known as genetic imprinting, and is also seen in Prader-Willi syndrome.

The most probable diagnosis for this patient would be Edward syndrome.Edward syndrome results from trisomy 18. It is the second most common syndrome after Down syndrome. 60% of cases die within 48 hours, and 90% within the first year due to apnoeas. Cardiovascular abnormalities include atrial septal defect, ventricular septal defect and a persistent ductus arteriosus. There is no association with exophthalmos, but it may occur. Right choroid plexus cysts are found on coronal imaging, and 40–70% at post mortem are shown to have multiple large bilateral choroid plexus cysts (>10 mm). These may not become pathological but usually trigger an anomaly scan. Around 1% of cases may present with only a cyst, but 4% may present with other abnormalities.Other options:- Children with the velocardiofacial syndrome have a classic facial appearance with hypertelorism, a tubular nose, a cleft lip/palate abnormality and cardiac anomalies. – Children with Patau syndrome usually present with midline defects and are less likely to have rocker-bottom feet. – Children with Treacher Collins syndrome present with abnormalities of the branchial arches and pharyngeal pouches.

Marfan syndrome is a disorder that affects the connective tissue found throughout the body, Marfan syndrome can affect many systems, often causing abnormalities in the heart, blood vessels, eyes, bones, and joints. The two primary features of Marfan syndrome are vision problems caused by a dislocated lens (ectopia lentis) in one or both eyes and aortic root disease, leading to aneurysmal dilatation, aortic regurgitation and dissection is the main cause of morbidity and mortality in Marfan syndrome.

Tuberous sclerosis, an autosomal dominant disorder, may present with a variety of symptoms, including seizures, developmental delay, behavioural problems, skin abnormalities, and lung and kidney disease. Hamartomas are often associated.

The physical features and developmental delay are the key aspects in the given scenario. The child in question shows features of gross motor and social developmental delay and has physical features indicative of Prader-Willi syndrome (hypopigmentation, esotropia, disproportionately small hands and feet, loss of central muscle tone and undescended testes). Children with Prader-Willi syndrome can present with failure to thrive until ,12-18 months, at which point, hyperphagia and obesity become more prominent. Other options:- Although Klinefelter syndrome can present with delayed development, undescended/small testes and reduced muscle power, the presence of small hands/feet, hypopigmentation and failure to thrive are not characteristic features. – Marfan syndrome presents with different physical features (arachnodactyly, cardio-respiratory complications and skin changes, amongst others) than those associated with Prader-Willi syndrome. – DiGeorge can manifest with developmental delay, hypotonia and feeding difficulties. However, this clinical scenario does not report any of the typical facial features, hearing abnormalities or cardiac abnormalities that are typically caused by DiGeorge syndrome. – Russell-Silver syndrome can cause developmental abnormalities, poor muscle tone and power (poor head control and muscle function), feeding difficulties and poor growth during the post-natal period and infancy. However, characteristic facial (small, triangular face, blue sclerae) and skeletal abnormalities (limb asymmetry, finger abnormalities) are not present. Therefore, Prader-Willi syndrome is the most appropriate diagnosis for this patient.Note:Prader-Willi syndrome is an example of genetic imprinting where the phenotype depends on whether the deletion occurs on a gene inherited from the mother or father: In Prader-Willi syndrome, it is the paternal gene that is deleted from the long arm of chromosome 15, while in Angelman syndrome the maternal gene is deleted. Prader-Willi syndrome can occur due to the microdeletion of paternal 15q11-13 (70% of cases) maternal uniparental disomy of chromosome 15.

Based on the clinical scenario provided, the most probable diagnosis for this patient would be tuberous sclerosis which is an autosomal dominant condition.Among the options provided, only Neurofibromatosis Type 1 is inherited by an autosomal dominant pattern. Other options:- Beckwith-Wiedemann syndrome is an example of an imprinting disorder and results from abnormalities of inheritance or methylation of chromosome 11p15.- Cystic fibrosis is an autosomal recessive condition.- Duchenne Muscular Dystrophy is an example of an X-linked recessive condition.- Hypophosphataemic (Vitamin D resistant) rickets is an X-linked dominant condition.

Ataxic gait is not a direct association of Down’s syndrome. All other given responses are associated with Down’s syndrome.

In humans, each cell normally contains 23 pairs of chromosomes, for a total of 46. Twenty-two of these pairs, called autosomes, look the same in both males and females. The 23rd pair, the sex chromosomes, differ between males and females. Females have two copies of the X chromosome, while males have one X and one Y chromosome.

Turner syndrome (TS) is one of the most common genetic disorders| occurs with an incidence of I: 2,500 female live births. It results from complete or partial chromosome X monosomy. TS is associated with abnormalities of the X chromosome and characteristic clinical features of short stature, gonadal dysgenesis, sexual developmental deficiencies, cardiac and/or renal defects, webbed neck, low-set ears, skeletal deformities including cubitus valgus, a propensity to ear infections and hearing deficits.

Congenital hypertrophy of the retinal pigment epithelium is one of FAP’s extra-intestinal manifestations. It appears in early childhood and affects an estimated 90% of those with FAP.

Advanced paternal age is associated with poor quality sperm leading to a reduction in overall fertility along with an increase in the occurrence of various medical disorders in the fetus. Advanced paternal age has been implicated as a risk factor for diseases like retinoblastoma, Marfan’s syndrome, neurofibromatosis, achondroplasia, autism spectrum disorders, schizophrenia, and acute lymphoblastic leukaemia. Down’s syndrome is mostly considered a consequence of advanced maternal age, but advanced paternal age has also been implicated as a risk factor. Turner syndrome is not found to be caused by advanced paternal age.

Haemophilia is a X-linked recessive disorder. In X-linked recessive inheritance only males are affected. An exception to this seen in examinations are patients with Turner’s syndrome, who are affected due to only having one X chromosome. X-linked recessive disorders are transmitted by heterozygote females (carriers) and male-to-male transmission is not seen. Affected males can only have unaffected sons and carrier daughters.

Individuals with Down syndrome are at increased risk for a variety of eye and vision disorders. Fortunately, many of these eye problems can be treated, especially if discovered at an early age. The quality of life can be further enhanced by the proper assessment and correction of eye problems. The most common eye findings include:- Refractive errors – Children with Down syndrome are more likely to need glasses than are other children. This may be due to myopia (near-sightedness), hyperopia (far-sightedness), and/or astigmatism. Refractive error may develop early in life or later on.- Strabismus – Between 20% and 60% of individuals with Down syndrome have eyes that are misaligned (strabismus). Esotropia (eyes that drift in) is most common while exotropia(eyes that drift out) occurs less frequently. Strabismus may be treated with glasses, patching and/or eye muscle surgery.- Keratoconus – A cone shaped distortion of the cornea (front layer of the eye), occurs in up to 30% of those with Down syndrome. Keratoconus is usually diagnosed around puberty and should be monitored regularly. Blurred vision, corneal thinning, or corneal haze may result from keratoconus. Keratoconus is worsened by eye rubbing| therefore, eye rubbing should be discouraged.- Cataracts – There is an increased incidence of congenital cataracts (present at birth) as well as acquired cataracts (develop later). Cataracts may progress slowly and should be monitored regularly, with surgical treatment performed when appropriate.- Glaucoma- There is an increased risk of infantile glaucoma (elevated pressure within the eye).- Blepharitis – Inflammation of the eyelids with redness at the edge of the lids and crusting around the lashes may occur and cause a feeling of dryness or burning. Treatment is with eyelid hygiene and topical antibiotics.- Tearing – Excessive tears or watering of the eyes may occur because the drainage channels are blocked or narrow (nasolacrimal duct obstruction). This may require surgical intervention.- Nystagmus – This is an involuntary “back-and-forth” movement or shaking of the eyes. It can affect vision to a mild or severe degree.

In this case, the affected individuals are all heterozygotes. Therefore, the mutation is autosomal dominant. Also, the mother does not carry the mutation, further confirming the autosomal dominant nature of the disease, which is most probably achondroplasia.

The autosomal dominant pattern of inheritance involves the presence of at least one of the defected copies of the gene in an individual to develop a specific diseased condition. Examples of this mode of inheritance include myotonic dystrophy, neurofibromatosis, achondroplasia, etc. Still’s disease, also called juvenile idiopathic arthritis, is not a heritable disease. Tay-Sachs disease is an autosomal recessive disease., while spinocerebellar ataxia and Friedreich’s ataxia are caused by trinucleotide repeat expansion.

Familial/inherited short stature is the most likely and commonest factor resulting in short stature among the children. Klinefelter syndrome is characterised by tall stature, widely spaces nipples and infertility. Other factors include congenital heart disease, maternal deprivation and diabetes mellitus but these are the rare causes.

Marfan syndrome is a disorder that affects the connective tissue in many parts of the body. Connective tissue provides strength and flexibility to structures such as bones, ligaments, muscles, blood vessels, and heart valves. The signs and symptoms of Marfan syndrome vary widely in severity, timing of onset, and rate of progression.This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder.At least 25 percent of Marfan syndrome cases result from a new mutation in the FBN1 gene. These cases occur in people with no history of the disorder in their family.The two primary features of Marfan syndrome are vision problems caused by a dislocated lens (ectopia lentis) in one or both eyes and defects in the large blood vessel that distributes blood from the heart to the rest of the body (the aorta).Associations include:Tall statureLearning disability (50%)Lens subluxation (usually upwards)Femoral herniaHemivertebraeCardiac problems (Aortic/mitral regurgitation, aneurysms)Joint hypermobilityArachnodactyly

These cardiovascular findings are suggestive of coarctation of the aorta, which is common among patients with Turner’s syndrome. Physical features of Turner’s syndrome include a short neck with a webbed appearance, a low hairline at the back of the head, low-set ears, and narrow fingernails and toenails that are turned upward.Atrioventricular septal defect is the most common cardiac anomaly in Down’s syndrome. Structural heart defects at birth (i.e., ventricular septal defect, atrial septal defect, patent ductus arteriosus) are common in Edward’s syndrome. Pulmonary stenosis with or without dysplastic pulmonary valve and hypertrophic cardiomyopathy are common in Noonan’s syndrome. Supravalvar aortic stenosis and peripheral pulmonary stenosis are found in William’s syndrome.

The correct answer is triple X syndrome with a genotype of XXX and an almost normal female phenotype. The extra X chromosome is inactive. The final phenotype of an individual is determined after normal sexual and gonadal differentiation, a process that involves several genes located on chromosomes X and Y. Disorders of sexual differentiation result in cases of ambiguous genitalia and are caused by a number of genetic abnormalities. Among these disorders is the turner syndrome with a genotype of 45X0, characterized by gonadal dysgenesis and ovarian failure. DAX-1 gene mutation leads to congenital adrenal hypoplasia and hypogonadotropic hypogonadism, which results in virilization of female external genitalia. Campomelic dysplasia results from mutation of the SOX-9 gene, leading to 46XY sex reversal. Danys-Drash syndrome is characterized by disordered sexual development in affected males due to the mutated WT-1 gene, which also causes Wilm’s tumour.

Klinefelter syndrome is a sex chromosome disorder in boys and men that results from the presence of an extra X chromosome in cells. People typically have 46 chromosomes in each cell, two of which are the sex chromosomes. Females have two X chromosomes (46,XX), and males have one X and one Y chromosome (46,XY). Most often, boys and men with Klinefelter syndrome have the usual X and Y chromosomes, plus one extra X chromosome, for a total of 47 chromosomes (47,XXY).Cri-du-chat (cat’s cry) syndrome, also known as 5p- (5p minus) syndrome, is a chromosomal condition that results when a piece of chromosome 5 is missing.Pierre Robin syndrome is not caused by a single gene defect but is a sequence.Meningomyelocele does not follow usual patterns of inheritance.

Klinefelter’s syndrome is the most common sex chromosome linked disorder with a karyotype of 47XXY. The incidence of the disease is 1 in 500-1000 male births. Childhood presentation consists of unusual growth spurt along with learning difficulties and delayed speech. The adolescence is marked by abnormal sexual maturation leading to hypogonadism and sub-fertility in adulthood.

Tay-Sachs disease is an autosomal recessive disease. For the brother to present with the disease, both parents must be carriers. Therefore, with each pregnancy the probability that the child would be affected is 1 in 4| the probability that the child would be a carrier is 2 in 4| and the probability that the child would be unaffected is also 1 in 4. Unaffected children have a 2 in 3 chance, or 66%, of becoming a carrier according to the patterns of autosomal recessive inheritance.

Familial adenomatous polyposis can have different inheritance patterns.When familial adenomatous polyposis results from mutations in the APC gene, it is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. In most cases, an affected person has one parent with the condition.When familial adenomatous polyposis results from mutations in the MUTYH gene, it is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. Most often, the parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but do not show signs and symptoms of the condition.