Superior margin of the scrotum superior to the base of the penis.

An increase in height of the medial longitudinal arch of the foot that does not flatten on weight bearing (i.e., a distinctly hollow form of the sole of the foot when it is bearing weight).

Syndactyly with fusion of toes four and five.

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

A height below that which is expected according to age and gender norms. Although there is no universally accepted definition of short stature, many refer to "short stature" as height more than 2 standard deviations below the mean for age and gender (or below the 3rd percentile for age and gender dependent norms).

Slow or limited growth after birth.

Feeding problem necessitating food and nutrient delivery via a tube.

A decreased magnitude of the sensory perception of sound.

Autism, the prototypic pervasive developmental disorder (PDD), is usually apparent by 3 years of age. It is characterized by a triad of limited or absent verbal communication, a lack of reciprocal social interaction or responsiveness, and restricted, stereotypic, and ritualized patterns of interests and behavior (Bailey et al., 1996; Risch et al., 1999). 'Autism spectrum disorder,' sometimes referred to as ASD, is a broader phenotype encompassing the less severe disorders Asperger syndrome (see ASPG1; 608638) and pervasive developmental disorder, not otherwise specified (PDD-NOS). 'Broad autism phenotype' includes individuals with some symptoms of autism, but who do not meet the full criteria for autism or other disorders. Mental retardation coexists in approximately two-thirds of individuals with ASD, except for Asperger syndrome, in which mental retardation is conspicuously absent (Jones et al., 2008). Genetic studies in autism often include family members with these less stringent diagnoses (Schellenberg et al., 2006). Levy et al. (2009) provided a general review of autism and autism spectrum disorder, including epidemiology, characteristics of the disorder, diagnosis, neurobiologic hypotheses for the etiology, genetics, and treatment options. Genetic Heterogeneity of Autism Autism is considered to be a complex multifactorial disorder involving many genes. Accordingly, several loci have been identified, some or all of which may contribute to the phenotype. Included in this entry is AUTS1, which has been mapped to chromosome 7q22. Other susceptibility loci include AUTS3 (608049), which maps to chromosome 13q14; AUTS4 (608636), which maps to chromosome 15q11; AUTS6 (609378), which maps to chromosome 17q11; AUTS7 (610676), which maps to chromosome 17q21; AUTS8 (607373), which maps to chromosome 3q25-q27; AUTS9 (611015), which maps to chromosome 7q31; AUTS10 (611016), which maps to chromosome 7q36; AUTS11 (610836), which maps to chromosome 1q41; AUTS12 (610838), which maps to chromosome 21p13-q11; AUTS13 (610908), which maps to chromosome 12q14; AUTS14A (611913), which has been found in patients with a deletion of a region of 16p11.2; AUTS14B (614671), which has been found in patients with a duplication of a region of 16p11.2; AUTS15 (612100), associated with mutation in the CNTNAP2 gene (604569) on chromosome 7q35-q36; AUTS16 (613410), associated with mutation in the SLC9A9 gene (608396) on chromosome 3q24; AUTS17 (613436), associated with mutation in the SHANK2 gene (603290) on chromosome 11q13; AUTS18 (615032), associated with mutation in the CHD8 gene (610528) on chromosome 14q11; AUTS19 (615091), associated with mutation in the EIF4E gene (133440) on chromosome 4q23; and AUTS20 (618830), associated with mutation in the NLGN1 gene (600568) on chromosome 3q26. (NOTE: the symbol 'AUTS2' has been used to refer to a gene on chromosome 7q11 (KIAA0442; 607270) and therefore is not used as a part of this autism locus series.) There are several X-linked forms of autism susceptibility: AUTSX1 (300425), associated with mutations in the NLGN3 gene (300336); AUTSX2 (300495), associated with mutations in NLGN4 (300427); AUTSX3 (300496), associated with mutations in MECP2 (300005); AUTSX4 (300830), associated with variation in the region on chromosome Xp22.11 containing the PTCHD1 gene (300828); AUTSX5 (300847), associated with mutations in the RPL10 gene (312173); and AUTSX6 (300872), associated with mutation in the TMLHE gene (300777). A locus on chromosome 2q (606053) associated with a phenotype including intellectual disability and speech deficits was formerly designated AUTS5. Folstein and Rosen-Sheidley (2001) reviewed the genetics of autism.

Dysarthric speech is a general description referring to a neurological speech disorder characterized by poor articulation. Depending on the involved neurological structures, dysarthria may be further classified as spastic, flaccid, ataxic, hyperkinetic and hypokinetic, or mixed.

Moderate mental retardation is defined as an intelligence quotient (IQ) in the range of 35-49.

A motor disorder characterized by a velocity-dependent increase in tonic stretch reflexes with increased muscle tone, exaggerated (hyperexcitable) tendon reflexes.

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.

Hyperreflexia is the presence of hyperactive stretch reflexes of the muscles.

Spasticity is manifested by increased stretch reflex which is intensified with movement velocity. This results in excessive and inappropriate muscle activation which can contribute to muscle hypertonia. Spastic gait is characterized by manifestations such as muscle hypertonia, stiff knee, and circumduction of the leg.

A degree of language development that is significantly below the norm for a child of a specified age.

A delay in the achievement of motor or mental milestones in the domains of development of a child, including motor skills, speech and language, cognitive skills, and social and emotional skills. This term should only be used to describe children younger than five years of age.

A type of ataxia characterized by the impairment of the ability to coordinate the movements required for normal walking. Gait ataxia is characteirzed by a wide-based staggering gait with a tendency to fall.

An abnormal gait pattern in which persons stand and walk with their feet spaced widely apart. This is often a component of cerebellar ataxia.

Complete lack of development of speech and language abilities.

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.

A condition in which there is increased muscle tone so that arms or legs, for example, are stiff and difficult to move.

Hypotonia is an abnormally low muscle tone (the amount of tension or resistance to movement in a muscle). Even when relaxed, muscles have a continuous and passive partial contraction which provides some resistance to passive stretching. Hypotonia thus manifests as diminished resistance to passive stretching. Hypotonia is not the same as muscle weakness, although the two conditions can co-exist.

A contracture of the Achilles tendon.

Muscular hypotonia (abnormally low muscle tone) affecting the musculature of the trunk.

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

Eczema is a form of dermatitis that is characterized by scaly, pruritic, erythematous lesions located on flexural surfaces.

An elevation of the level of the enzyme creatine kinase (also known as creatine phosphokinase (CK; EC 2.7.3.2) in the blood. CK levels can be elevated in a number of clinical disorders such as myocardial infarction, rhabdomyolysis, and muscular dystrophy.

An elevated level of the enzyme lactate dehydrogenase in the blood circulation.

A fixed reduction in the vertical distance between the upper and lower eyelids with short palpebral fissures.

Distance between the inner canthi more than two standard deviations above the mean (objective); or, apparently increased distance between the inner canthi.

Distance between subnasale and pronasale more than two standard deviations above the mean, or alternatively, an apparently increased anterior protrusion of the nasal tip.

Flat skin surface, with no ridge formation in the central region of the upper lip between the nasal base and upper vermilion border.

Thinned, deficient, or excessively arched ala nasi.

Facial height (length) is more than 2 standard deviations above the mean (objective); or, an apparent increase in the height (length) of the face (subjective).

Bizygomatic (upper face) and bigonial (lower face) width are both more than 2 standard deviations below the mean (objective); or, an apparent reduction in the width of the upper and lower face (subjective).

Height of the vermilion of the upper lip in the midline more than 2 SD above the mean. Alternatively, an apparently increased height of the vermilion of the upper lip in the frontal view (subjective).

Increased breadth of the nasal bridge (and with it, the nasal root).

Increased density/number and/or increased diameter of eyebrow hairs.

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

Distance between nasal base and midline upper lip vermilion border more than 2 SD below the mean. Alternatively, an apparently decreased distance between nasal base and midline upper lip vermilion border.

Decreased vertical distance from the vermilion border of the lower lip to the inferior-most point of the chin.

Meeting of the medial eyebrows in the midline.

Reduced density of hairs.

The presence of nipples that instead of pointing outward are retracted inwards.

Although hypertelorism means an excessive distance between any paired organs (e.g., the nipples), the use of the word has come to be confined to ocular hypertelorism. Hypertelorism occurs as an isolated feature and is also a feature of many syndromes, e.g., Opitz G syndrome (see 300000), Greig cephalopolysyndactyly (175700), and Noonan syndrome (163950) (summary by Cohen et al., 1995).

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.

Nystagmus consisting of horizontal to-and-fro eye movements.

Interpupillary distance less than 2 SD below the mean (alternatively, the appearance of an decreased interpupillary distance or closely spaced eyes).