Cryptorchidism, or failure of testicular descent, is a common human congenital abnormality with a multifactorial etiology that likely reflects the involvement of endocrine, environmental, and hereditary factors. Cryptorchidism can result in infertility and increases risk for testicular tumors. Testicular descent from abdomen to scrotum occurs in 2 distinct phases: the transabdominal phase and the inguinoscrotal phase (summary by Gorlov et al., 2002).

Increased levels of protein in the urine.

A reduction in the level of performance of the kidneys in areas of function comprising the concentration of urine, removal of wastes, the maintenance of electrolyte balance, homeostasis of blood pressure, and calcium metabolism.

Abnormally small penis. At birth, the normal penis is about 3 cm (stretched length from pubic tubercle to tip of penis) with micropenis less than 2.0-2.5 cm.

Sclerosis of the epiphyses of the phalanges of the fingers, leading to an increased degree of radiopacity (white or ivory appearance) in X-rays.

Any cardiac rhythm other than the normal sinus rhythm. Such a rhythm may be either of sinus or ectopic origin and either regular or irregular. An arrhythmia may be due to a disturbance in impulse formation or conduction or both.

The presence of chronic increased pressure in the systemic arterial system.

A severe degree of short stature, more than -4 SD from the mean corrected for age and sex.

An abnormal restriction of fetal growth with fetal weight below the tenth percentile for gestational age.

Smaller than normal size according to sex and gestational age related norms, defined as a weight below the 10th percentile for the gestational age.

Slow or limited growth after birth.

Failure to thrive (FTT) refers to a child whose physical growth is substantially below the norm.

Abnormally increased size of the liver.

A type of hearing impairment in one or both ears related to an abnormal functionality of the cochlear nerve.

An abnormality of the pinna, which is also referred to as the auricle or external ear.

Cerebellar ataxia refers to ataxia due to dysfunction of the cerebellum. This causes a variety of elementary neurological deficits including asynergy (lack of coordination between muscles, limbs and joints), dysmetria (lack of ability to judge distances that can lead to under- or overshoot in grasping movements), and dysdiadochokinesia (inability to perform rapid movements requiring antagonizing muscle groups to be switched on and off repeatedly).

Normal-pressure hydrocephalus-1 (HYDNP1) is an autosomal dominant neurologic disorder characterized by the clinical triad of slowly progressive gait instability, urinary incontinence, and cognitive decline associated with ventricular enlargement on brain imaging with normal pressure of the cerebrospinal fluid (CSF). The onset of symptoms is usually in late adulthood; the symptoms are responsive to shunting. The disorder has been associated with recurrent respiratory infections and possible infertility issues, but the latter has not been confirmed (summary by Takahashi et al., 2011 and Morimoto et al., 2019).

A seizure is an intermittent abnormality of nervous system physiology characterized by a transient occurrence of signs and/or symptoms due to abnormal excessive or synchronous neuronal activity in the brain.

An unintentional, oscillating to-and-fro muscle movement about a joint axis.

A generalized disorder of peripheral nerves.

Atrophy (wasting, decrease in size of cells or tissue) affecting the cerebrum.

An anomaly of visually evoked potentials (VEP), which are electrical potentials, initiated by brief visual stimuli, which are recorded from the scalp overlying the visual cortex.

An abnormality of the auditory evoked potentials, which are used to trace the signal generated by a sound, from the cochlear nerve, through the lateral lemniscus, to the medial geniculate nucleus, and to the cortex.

Patchy loss of myelin from nerve fibers in the central nervous system.

A reduction in the speed at which electrical signals propagate along the axon of a neuron.

Intellectual disability, previously referred to as mental retardation, is characterized by subnormal intellectual functioning that occurs during the developmental period. It is defined by an IQ score below 70.

Defective structure and function of myelin sheaths. Dysmyelination is distinguished from demyleination where there is destruction or damage of previously normal myelination.

An abnormality of the myelination of motor and sensory peripheral nerves. These are axons for motor nerves and dendrites for sensory nerves in the strict anatomic sense.

Exaggerated anterior convexity of the thoracic vertebral column.

Osteoporosis is a systemic skeletal disease characterized by low bone density and microarchitectural deterioration of bone tissue with a consequent increase in bone fragility. According to the WHO criteria, osteoporosis is defined as a BMD that lies 2.5 standard deviations or more below the average value for young healthy adults (a T-score below -2.5 SD).

Reduced strength of muscles.

The presence of calcium deposition affecting one or more structures of the basal ganglia.

Loss of normal subcutaneous fat tissue in the face.

An abnormally squared appearance of the bony pelvis, a normally rounded or basin-shaped structure.

A reduction in the freedom of movement of one or more joints.

A reduced amount of fat tissue in the lowest layer of the integument. This feature can be appreciated by a reduced skinfold thickness.

The presence of an abnormally thick calvaria.

Underdevelopment of the ilium ala.

Underdevelopment of the bony pelvis.

Atypically scarred skin .

Head circumference below 2 standard deviations below the mean for age and gender.

Abnormal increased size of the spleen.

Caries is a multifactorial bacterial infection affecting the structure of the tooth. This term has been used to describe the presence of more than expected dental caries.

Dental malocclusion refers to an abnormality of the occlusion, or alignment, of the teeth and the way the upper and lower teeth fit together, resulting in overcrowding of teeth or in abnormal bite patterns.

Developmental hypoplasia of teeth.

Abnormal prominence of the chin related to increased length of the mandible.

Facial contour, as viewed from the front, triangular in shape, with breadth at the temples and tapering to a narrow chin.

Delayed tooth eruption affecting the primary dentition.

Anterior positioning of the nasal root in comparison to the usual positioning for age.

Inability to sweat.

Partial or complete wasting (atrophy) of the skin.

Skin characterized by the lack of natural or normal moisture.

An abnormality of the hair.

Hair that lacks the luster (shine or gleam) of normal hair.

An increased sensitivity of the skin to light. Photosensitivity may result in a rash upon exposure to the sun (which is known as photodermatosis). Photosensitivity can be diagnosed by phototests in which light is shone on small areas of skin.

An abnormality of the pigmentation of the skin.

A degree of wrinkling of the facial skin that is more than expected for the age of the individual, leading to a prematurely aged appearance.

Reduced density of hairs.

A cataract that occurs congenitally as the result of a developmental defect, in contrast to the majority of cataracts that occur in adulthood as the result of degenerative changes of the lens.

An abnormality of refraction characterized by the ability to see objects in the distance clearly, while objects nearby appear blurry.

Microphthalmia is an eye abnormality that arises before birth. In this condition, one or both eyeballs are abnormally small. In some affected individuals, the eyeball may appear to be completely missing; however, even in these cases some remaining eye tissue is generally present. Such severe microphthalmia should be distinguished from another condition called anophthalmia, in which no eyeball forms at all. However, the terms anophthalmia and severe microphthalmia are often used interchangeably. Microphthalmia may or may not result in significant vision loss.\n\nPeople with microphthalmia may also have a condition called coloboma. Colobomas are missing pieces of tissue in structures that form the eye. They may appear as notches or gaps in the colored part of the eye called the iris; the retina, which is the specialized light-sensitive tissue that lines the back of the eye; the blood vessel layer under the retina called the choroid; or in the optic nerves, which carry information from the eyes to the brain. Colobomas may be present in one or both eyes and, depending on their size and location, can affect a person's vision.\n\nPeople with microphthalmia may also have other eye abnormalities, including clouding of the lens of the eye (cataract) and a narrowed opening of the eye (narrowed palpebral fissure). Additionally, affected individuals may have an abnormality called microcornea, in which the clear front covering of the eye (cornea) is small and abnormally curved.\n\nBetween one-third and one-half of affected individuals have microphthalmia as part of a syndrome that affects other organs and tissues in the body. These forms of the condition are described as syndromic. When microphthalmia occurs by itself, it is described as nonsyndromic or isolated.

Rhythmic, involuntary oscillations of one or both eyes related to abnormality in fixation, conjugate gaze, or vestibular mechanisms.

Atrophy of the optic nerve. Optic atrophy results from the death of the retinal ganglion cell axons that comprise the optic nerve and manifesting as a pale optic nerve on fundoscopy.

A misalignment of the eyes so that the visual axes deviate from bifoveal fixation. The classification of strabismus may be based on a number of features including the relative position of the eyes, whether the deviation is latent or manifest, intermittent or constant, concomitant or otherwise and according to the age of onset and the relevance of any associated refractive error.

Abnormally decreased lacrimation, that is, reduced ability to produce tears.

A congenital abnormality of the cornea in which the cornea and the anterior segment of the eye are smaller than normal. The horizontal diameter of the cornea does not reach 10 mm even in adulthood.

Congenital underdevelopment of the iris.

An eye that is more deeply recessed into the plane of the face than is typical.

Reduced transparency of the stroma of cornea.

An abnormality of the retina characterized by pigment deposition. It is typically associated with migration and proliferation of macrophages or retinal pigment epithelial cells into the retina; melanin from these cells causes the pigmentary changes. Pigmentary retinopathy is a common final pathway of many retinal conditions and is often associated with visual loss.