Spinal and bulbar muscular atrophy (SBMA), also known as Kennedy's disease, is a severe neurodegenerative syndrome that is associated with a particular mutation of the androgen receptor's polyglutamine tract called a trinucleotide repeat expansion. SBMA results when the length of the polyglutamine tract exceeds 40 repetitions.

Although technically a variant of MAIS, SBMA's presentation is not typical of androgen insensitivity; symptoms do not occur until adulthood and include neuromuscular defects as well as signs of androgen inaction. Neuromuscular symptoms include progressive proximal muscle weakness, atrophy, and fasciculations. Symptoms of androgen insensitivity experienced by men with SBMA are also progressive and include testicular atrophy, severe oligospermia or azoospermia, gynecomastia, and feminized skin changes despite elevated androgen levels. Disease onset, which usually affects the proximal musculature first, occurs in the third to fifth decades of life, and is often preceded by muscular cramps on exertion, tremor of the hands, and elevated muscle creatine kinase. SBMA is often misdiagnosed as amyotrophic lateral sclerosis (ALS) (also known as Lou Gehrig's disease).

The symptoms of SBMA are thought to be brought about by two simultaneous pathways involving the toxic misfolding of proteins and loss of AR functionality. The polyglutamine tract in affected pedigrees tends to increase in length over generations, a phenomenon known as "anticipation", leading to an increase in the severity of the disease as well as a decrease in the age of onset for each subsequent generation of a family affected by SBMA.

Individuals with mild (or minimal) androgen insensitivity syndrome (grade 1 on the Quigley scale) are born phenotypically male, with fully masculinized genitalia; this category of androgen insensitivity is diagnosed when the degree of androgen insensitivity in an individual with a 46,XY karyotype is great enough to impair virilization or spermatogenesis, but is not great enough to impair normal male genital development. MAIS is the mildest and least known form of androgen insensitivity syndrome.

The existence of a variant of androgen insensitivity that solely affected spermatogenesis was theoretical at first. Cases of phenotypically normal males with isolated spermatogenic defect due to AR mutation were first detected as the result of male infertility evaluations. Until then, early evidence in support of the existence of MAIS was limited to cases involving a mild defect in virilization, although some of these early cases made allowances for some degree of impairment of genital masculinization, such as hypospadias or micropenis. It is estimated that 2-3% of infertile men have AR gene mutations.

Examples of MAIS phenotypes include isolated infertility (oligospermia or azoospermia), mild gynecomastia in young adulthood, decreased secondary terminal hair, high pitched voice, or minor hypospadias repair in childhood. The external male genitalia (penis, scrotum, and urethra) are otherwise normal in individuals with MAIS. Internal genitalia, including Wolffian structures (the epididymides, vasa deferentia, and seminal vesicles) and the prostate, is also normal, although the bitesticular volume of infertile men (both with and without MAIS) is diminished; male infertility is associated with reduced bitesticular volume, varicocele, retractile testes, low ejaculate volume, male accessory gland infections (MAGI), and mumps orchitis. The incidence of these features in infertile men with MAIS is similar to that of infertile men without MAIS. MAIS is not associated with Müllerian remnants.

AIS is broken down into three classes based on phenotype: complete androgen insensitivity syndrome (CAIS), partial androgen insensitivity syndrome (PAIS), and mild androgen insensitivity syndrome (MAIS). A supplemental system of phenotypic grading that uses seven classes instead of the traditional three was proposed by pediatric endocrinologist Charmian A. Quigley et al. in 1995. The first six grades of the scale, grades 1 through 6, are differentiated by the degree of genital masculinization; grade 1 is indicated when the external genitalia is fully masculinized, grade 6 is indicated when the external genitalia is fully feminized, and grades 2 through 5 quantify four degrees of decreasingly masculinized genitalia that lie in the interim. Grade 7 is indistinguishable from grade 6 until puberty, and is thereafter differentiated by the presence of secondary terminal hair; grade 6 is indicated when secondary terminal hair is present, whereas grade 7 is indicated when it is absent. The Quigley scale can be used in conjunction with the traditional three classes of AIS to provide additional information regarding the degree of genital masculinization, and is particularly useful when the diagnosis is PAIS.

Androgen insensitivity syndrome (AIS) is an intersex condition in which there is a partial or complete inability of many cells in the affected genetic male to respond to androgenic hormones. This can prevent or impair the masculinization of male genitalia in the developing genetic male (chromosomal XY) fetus, as well as the development of male secondary sexual characteristics at puberty. Clinical phenotypes range from a normal male habitus with mild spermatogenic defect or reduced secondary terminal hair; to a full female habitus despite the presence of a Y-chromosome. Women (chromosomal XX) who are heterozygous for the AR gene have normal primary and secondary sexual characteristics; this female carrier will pass the affected AR gene to any child she has with 50% likelihood. AIS is the largest single entity that leads to 46,XY undermasculinized genitalia.

The androgen receptor (AR), which is defective due to a mutation in most of these syndromes, is a type of nuclear receptor that is activated by binding to either of the androgenic hormones (testosterone or dihydrotestosterone) in the cytoplasm, and then translocates into the nucleus where it binds to DNA, provided androgen response elements and coactivators are present. This combination functions as a transcription complex to turn on androgen gene expression. Thus the AR activates these genes to mediate the effects of androgens in the human body, including the development and maintenance of the male sexual phenotype and generalized anabolic effects. Over 400 AR mutations have been reported.

AIS is divided into three categories that are differentiated by the degree of genital masculinization: complete androgen insensitivity syndrome (CAIS) is indicated when the external genitalia are that of a normal female; mild androgen insensitivity syndrome (MAIS) is indicated when the external genitalia are that of a normal male, and partial androgen insensitivity syndrome (PAIS) is indicated when the external genitalia are partially, but not fully, masculinized.

Management of AIS is currently limited to symptomatic management; no method is currently available to correct the malfunctioning androgen receptor proteins produced by "AR" gene mutations. Areas of management include sex assignment, genitoplasty, gonadectomy in relation to tumor risk, hormone replacement therapy, genetic counseling, and psychological counseling.

As babies and children, XXY males may have weaker muscles and reduced strength. As they grow older, they tend to become taller than average. They may have less muscle control and coordination than other boys of their age.

During puberty, the physical traits of the syndrome become more evident; because these boys do not produce as much testosterone as other boys, they have a less muscular body, less facial and body hair, and broader hips. As teens, XXY males may develop breast tissue and also have weaker bones, and a lower energy level than other males.

By adulthood, XXY males look similar to males without the condition, although they are often taller. In adults, possible characteristics vary widely and include little to no sign of affectedness, a , youthful build and facial appearance, or a rounded body type with some degree of gynecomastia (increased breast tissue). Gynecomastia is present to some extent in about a third of affected individuals, a slightly higher percentage than in the XY population. About 10% of XXY males have gynecomastia noticeable enough that they may choose to have cosmetic surgery.

Affected males are often infertile, or may have reduced fertility. Advanced reproductive assistance is sometimes possible.

The term "hypogonadism" in XXY symptoms is often misinterpreted to mean "small testicles" when it means decreased testicular hormone/endocrine function. Because of this (primary) hypogonadism, individuals will often have a low serum testosterone level but high serum follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels. Despite this misunderstanding of the term, however, it is true that XXY men may also have microorchidism (i.e., small testicles).

The testicle size of affected males are usually less than 2 cm in length (and always shorter than 3.5 cm), 1 cm in width and 4 ml in volume.

XXY males are also more likely than other men to have certain health problems that typically affect females, such as autoimmune disorders, breast cancer, venous thromboembolic disease, and osteoporosis. In contrast to these potentially increased risks, it is currently thought that rare X-linked recessive conditions occur less frequently in XXY males than in normal XY males, since these conditions are transmitted by genes on the X chromosome, and people with two X chromosomes are typically only carriers rather than affected by these X-linked recessive conditions.

Some degree of language learning or reading impairment may be present, and neuropsychological testing often reveals deficits in executive functions, although these deficits can often be overcome through early intervention. There may also be delays in motor development which can be addressed through occupational therapy and physical therapy. XXY males may sit up, crawl, and walk later than other infants; they may also struggle in school, both academically and with sports.

Spermatogenesis arrest is a complex process of interruption in the differentiation of germinal cells of specific cellular type, which elicits an altered spermatozoa formation. Spermatogenic arrest is usually due to genetic factors resulting in irreversible azoospermia. However some cases may be consecutive to hormonal, thermic, or toxic factors and may be reversible either spontaneously or after a specific treatment.

Many men who were born with undescended testes have reduced fertility, even after orchiopexy in infancy. The reduction with unilateral cryptorchidism is subtle, with a reported infertility rate of about 10%, compared with about 6% reported by the same study for the general population of adult men.

The fertility reduction after orchiopexy for bilateral cryptorchidism is more marked, about 38%, or 6 times that of the general population. The basis for the universal recommendation for early surgery is research showing degeneration of spermatogenic tissue and reduced spermatogonia counts after the second year of life in undescended testes. The degree to which this is prevented or improved by early orchiopexy is still uncertain.

There is a small body of research on the psychology of cryptorchidism, that attempts to determine whether this condition can cause lasting psychological problems. The psychological research on cryptorchism consists of only a few case reports and small studies. This research also has serious methodological problems: major variables are completely uncontrolled, such as the small physical stature of many cryptorchid boys, and the psychological effects of corrective surgery.

Existing research indicates that boys with undescended testicles do not tend to be gender-disordered, effeminate, or pre-homosexual. A disturbed self-image forms only when the family dynamics are destructive to developing male self-esteem. Such pathogenic attitudes were found in parents who focused on the boy’s genital defect as a sign of his presumed effeminacy. However, when the cryptorchism is surgically corrected a healthy masculinity becomes possible. The basic sexual normality of these boys was confirmed in a small retrospective study that tested adolescent boys several years after their condition was surgically repaired. They had developed into fairly well-adjusted teenagers without special sexual or gender problems, and with no distinctive traits of psychopathological relevance.

The testicle or testis is the male reproductive gland in all animals, including humans. It is homologous to the female ovary. The functions of the testes are to produce both sperm and androgens, primarily testosterone. Testosterone release is controlled by the anterior pituitary luteinizing hormone; whereas sperm production is controlled both by the anterior pituitary follicle-stimulating hormone and gonadal testosterone.

Testicular enlargement is an unspecific sign of various testicular diseases, and can be defined as a testicular size of more than 5 cm (long axis) x 3 cm (short axis).

Blue balls is a slang term for a temporary fluid congestion in the testicles and prostate region caused by prolonged sexual arousal.

Testicular prostheses are available to mimic the appearance and feel of one or both testicles, when absent as from injury or as treatment in association to gender dysphoria. There have also been some instances of their implantation in dogs.

The presenting characteristics of DDS include loss of playfulness, decreased appetite, weight loss, growth delay, abnormal skeletal development, insomnia, abdominal pain, constipation, and anuria.

Clinically, Denys–Drash is characterized by the triad of pseudohermaphroditism, mesangial renal sclerosis, and Wilms' tumor. The condition first manifests as early nephrotic syndrome and progresses to mesangial renal sclerosis, and ultimately renal failure—usually within the first three years of life.

Infants with the disorder exhibit an inverted smile; they appear to be crying when they are actually smiling, in conjunction with uropathy. They also may be affected by hydronephrosis. Symptoms of this disease can start at very young ages. Many people with this syndrome will die in their teens to early 20s because of the renal failure (uropathy) if not diagnosed and treated. Children with the syndrome have abnormal facial development that cause an inverted smile, nerve connections are however normal. When attempting to smile, the child will appear to cry. Urinary problems arise as a result of a neurogenic bladder. Most patients older than the age of toilet training, present with enuresis, urinary-tract infection, hydronephrosis, and a spectrum of radiological abnormalities typical of obstructive or neurogenic bladders. Radiological abnormalities include things such as: trabeculated bladder, vesicoureteral reflex, external sphincter spasm, pyelonephritis, hyperreflexic bladder, noninhibited detrusor contraction, etc.. Urinary abnormalities might result in renal deterioration and failure. This can be prevented by taking proper measures to restore normal micturition and by taking antibiotics to prevent infections. In some cases, the affected patients become hypertensive and progress to end-stage renal disease, while others become uremic. Additionally, most patients suffer from constipation.

Early detection of this syndrome is possible through the peculiar faces that children present.

Urofacial syndrome ( or hydronephrosis with peculiar facial expression), is an autosomal recessive congenital disorder characterized by inverted facial expressions in association with obstructive disease of the urinary tract. The inverted facial expression presented by children with this syndrome allows for early detection of the syndrome, this inverted smile is easy to see when the child is smiling and laughing. Early detection is vital for establishing a better prognosis as urinary related problems associated with this disease can cause harm if left untreated. Incontinence is another easily detectable symptom of the syndrome that is due to detrusor-sphincter discoordination, although it can easily be mistaken for pyelonephritis.

It may be associated with "HPSE2".

Denys–Drash syndrome (DDS) or Drash syndrome is a rare disorder or syndrome characterized by gonadal dysgenesis, nephropathy, and Wilms' tumor.

Complete trisomy 8 causes severe effects on the developing fetus and can be a cause of miscarriage.

Complete trisomy 8 is usually an early lethal condition, whereas trisomy 8 mosaicism is less severe and individuals with a low proportion of affected cells may exhibit a comparatively mild range of physical abnormalities and developmental delay. Individuals with trisomy 8 mosaicism are more likely to survive into childhood and adulthood, and exhibit a characteristic and recognizable pattern of developmental abnormalities. Common findings include retarded psychomotor development, moderate to severe mental retardation, variable growth patterns which can result in either abnormally short or tall stature, an expressionless face, and many musculoskeletal, visceral, and eye abnormalities, as well as other anomalies. A deep plantar furrow is considered to be pathognomonic of this condition, especially when seen in combination with other associated features. The type and severity of symptoms are dependent upon the location and proportion of trisomy 8 cells compared to normal cells.

Microlissencephaly Type B or Barth microlissencephaly syndrome: is a microlissencephaly with thick cortex, severe cerebellar and brainstem hypoplasia. The Barth-type of MLIS is the most severe of all the known lissencephaly syndromes.

This phenotype consists of polyhydramnios (probably due to poor fetal swallowing), severe congenital microcephaly, weak respiratory effort, and survival for only a few hours or days. Barth described two siblings with this type as having a very low brainweight, wide ventricles, a very thin neopallium, absent corpus callosum and absent olfactory nerve.

Microlissencephalic patients suffer from spasticity, seizures, severe developmental delay and intellectual disabilities with survival varying from days to years. Patients may also have dysmorphic craniofacial features, abnormal genitalia, and arthrogryposis.

Microlissencephaly may arise as a part of Baraitser-Winter syndrome which comprises also ptosis, coloboma, hearing loss and learning disability.

Moreover, it is the distinct developmental brain abnormality in "microcephalic osteodysplastic primordial dwarfism" (MOPD1). Microlissencephaly may be accompanied by micromelia as in Basel-Vanagaite-Sirota syndrome ( Microlissencephaly-Micromelia syndrome).

Trisomy 8, also known as Warkany syndrome 2, is a human chromosomal disorder caused by having three copies (trisomy) of chromosome 8. It can appear with or without mosaicism.

Sirenomelia, alternatively known as Mermaid syndrome, is a rare congenital deformity in which the legs are fused together, giving them the appearance of a mermaid's tail as the nickname suggests.

This condition is found in approximately one out of every 100,000 live births (about as rare as conjoined twins) and is usually fatal within a day or two of birth because of complications associated with abnormal kidney and urinary bladder development and function. More than half the cases of sirenomelia result in stillbirth and this condition is 100 times more likely to occur in identical twins than in single births or fraternal twins. It results from a failure of normal vascular supply from the lower aorta in utero. Maternal diabetes has been associated with caudal regression syndrome and sirenomelia, although a few sources question this association.

VACTERL-H is an expanded form of the VACTERL association that concludes that this diagnosis is a less severe form of sirenomelia. The disorder was formerly thought to be an extreme case of caudal regression syndrome; however, it was reclassified to be considered a separate condition.

Affected male and carrier female dogs generally begin to show signs of the disease at two to three months of age, with proteinuria. By three to four months of age, symptoms include for affected male dogs: bodily wasting and loss of weight, proteinuria & hypoalbuminemia. Past nine months of age, hypercholesterolemia may be seen. In the final stages of the disease, at around 15 months of age for affected males, symptoms are reported as being renal failure, hearing loss and death. Since the condition is genetically dominant, diagnosis would also include analysis of the health of the sire and dam of the suspected affected progeny if available.

Familial hyperaldosteronism is a group of inherited conditions in which the adrenal glands, which are small glands located on top of each kidney, produce too much of the hormone aldosterone. Excess aldosterone causes the kidneys to retain more salt than normal, which in turn increases the body's fluid levels and causes high blood pressure. People with familial hyperaldosteronism may develop severe high blood pressure, often early in life. Without treatment, hypertension increases the risk of strokes, heart attacks, and kidney failure. There are other forms of hyperaldosteronism that are not inherited.

Familial hyperaldosteronism is categorized into three types, distinguished by their clinical features and genetic causes. In familial hyperaldosteronism type I, hypertension generally appears in childhood to early adulthood and can range from mild to severe. This type can be treated with steroid medications called glucocorticoids, so it is also known as glucocorticoid-remediable aldosteronism (GRA). In familial hyperaldosteronism type II, hypertension usually appears in early to middle adulthood and does not improve with glucocorticoid treatment. In most individuals with familial hyperaldosteronism type III, the adrenal glands are enlarged up to six times their normal size. These affected individuals have severe hypertension that starts in childhood. The hypertension is difficult to treat and often results in damage to organs such as the heart and kidneys. Rarely, individuals with type III have milder symptoms with treatable hypertension and no adrenal gland enlargement.

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. The various types of familial hyperaldosteronism have different genetic causes.

It is unclear how common these diseases are. All together they appear to make up less than 1% of cases of hyperaldosteronism.

Only a few individuals who did not have fatal kidney and bladder complications are known to have survived beyond birth with this condition.

The precise symptoms of a primary immunodeficiency depend on the type of defect. Generally, the symptoms and signs that lead to the diagnosis of an immunodeficiency include recurrent or persistent infections or developmental delay as a result of infection. Particular organ problems (e.g. diseases involving the skin, heart, facial development and skeletal system) may be present in certain conditions. Others predispose to autoimmune disease, where the immune system attacks the body's own tissues, or tumours (sometimes specific forms of cancer, such as lymphoma). The nature of the infections, as well as the additional features, may provide clues as to the exact nature of the immune defect.

Galactokinase deficiency, also known as Galactosemia type 2 or GALK deficiency, is an autosomal recessive metabolic disorder marked by an accumulation of galactose and galactitol secondary to the decreased conversion of galactose to galactose-1-phosphate by galactokinase. The disorder is caused by mutations in the GALK1 gene, located on chromosome 17q24. Galactokinase catalyzes the first step of galactose phosphorylation in the Leloir pathway of intermediate metabolism. Galactokinase deficiency is one of the three inborn errors of metabolism that lead to hypergalactosemia. The disorder is inherited as an autosomal recessive trait. Unlike classic galactosemia, which is caused by deficiency of galactose-1-phosphate uridyltransferase, galactokinase deficiency does not present with severe manifestations in early infancy. Its major clinical symptom is the development of cataracts during the first weeks or months of life, as a result of the accumulation, in the lens, of galactitol, a product of an alternative route of galactose utilization. The development of early cataracts in homozygous affected infants is fully preventable through early diagnosis and treatment with a galactose-restricted diet. Some studies have suggested that, depending on milk consumption later in life, heterozygous carriers of galactokinase deficiency may be prone to presenile cataracts at 20–50 years of age.