MedGen

Smith-Magenis syndrome (SMS) is characterized by distinctive physical features (particularly coarse facial features that progress with age), developmental delay, cognitive impairment, behavioral abnormalities, sleep disturbance, and childhood-onset abdominal obesity. Infants have feeding difficulties, failure to thrive, hypotonia, hyporeflexia, prolonged napping or need to be awakened for feeds, and generalized lethargy. The majority of individuals function in the mild-to-moderate range of intellectual disability. The behavioral phenotype, including significant sleep disturbance, stereotypies, and maladaptive and self-injurious behaviors, is generally not recognized until age 18 months or older and continues to change until adulthood. Sensory issues are frequently noted; these may include avoidant behavior, as well as repetitive seeking of textures, sounds, and experiences. Toileting difficulties are common. Significant anxiety is common as are problems with executive functioning, including inattention, distractibility, hyperactivity, and impulsivity. Maladaptive behaviors include frequent outbursts / temper tantrums, attention-seeking behaviors, opposition, aggression, and self-injurious behaviors including self-hitting, self-biting, skin picking, inserting foreign objects into body orifices (polyembolokoilamania), and yanking fingernails and/or toenails (onychotillomania). Among the stereotypic behaviors described, the spasmodic upper-body squeeze or "self-hug" seems to be highly associated with SMS. An underlying developmental asynchrony, specifically emotional maturity delayed beyond intellectual functioning, may also contribute to maladaptive behaviors in people with SMS. [from GeneReviews]

Williams syndrome (WS) is characterized by cardiovascular disease (elastin arteriopathy, peripheral pulmonary stenosis, supravalvar aortic stenosis, hypertension), distinctive facies, connective tissue abnormalities, intellectual disability (usually mild), a specific cognitive profile, unique personality characteristics, growth abnormalities, and endocrine abnormalities (hypercalcemia, hypercalciuria, hypothyroidism, and early puberty). Feeding difficulties often lead to poor weight gain in infancy. Hypotonia and hyperextensible joints can result in delayed attainment of motor milestones. [from GeneReviews]

Cri-du-chat syndrome was first described by Lejeune et al. (1963) as a hereditary congenital syndrome associated with deletion of part of the short arm of chromosome 5. The deletions can vary in size from extremely small and involving only band 5p15.2 to the entire short arm. Although the majority of deletions arise as new mutations, approximately 12% result from unbalanced segregation of translocations or recombination involving a pericentric inversion in one of the parents. [from OMIM]

Acute infantile GM2 activator deficiency is a neurodegenerative disorder in which infants, who are generally normal at birth, have progressive weakness and slowing of developmental progress between ages four and 12 months. An ensuing developmental plateau is followed by progressively rapid developmental regression. By the second year of life decerebrate posturing, difficulty in swallowing, and worsening seizures lead to an unresponsive vegetative state. Death usually occurs between ages two and three years. [from GeneReviews]

Arnold-Chiari type I malformation refers to a relatively mild degree of herniation of the posteroinferior region of the cerebellum (the cerebellar tonsils) into the cervical canal with little or no displacement of the fourth ventricle. It is characterized by one or both pointed (not rounded) cerebellar tonsils that project 5 mm below the foramen magnum, measured by a line drawn from the basion to the opisthion (McRae Line) [from HPO]

TRIO-related intellectual disability (ID) is characterized by delay in acquisition of motor and language skills, mild to borderline intellectual disability, and neurobehavioral problems (including autistic traits or autism spectrum disorder, attention-deficit/hyperactivity disorder, and/or aggression). Neonatal or infantile feeding difficulties including poor suck, impaired bottle feeding, and failure to thrive are common and are often the presenting finding. Other findings can include microcephaly, variable hand and dental abnormalities, and suggestive facial features. Only ten of the 20 individuals with a TRIO pathogenic variant reported to date had sufficient information to make preliminary generalizations about clinical manifestations; it is anticipated that the phenotype of this newly described disorder will continue to evolve. [from GeneReviews]

The chromosome 8q21.11 deletion syndrome is characterized by impaired intellectual development and common facial dysmorphic features (summary by Palomares et al., 2011). [from OMIM]

Jansen-de Vries syndrome (JDVS) is an autosomal dominant neurodevelopmental disorder characterized by delayed psychomotor development, intellectual disability with speech delay, and behavioral abnormalities. Most patients have variable additional features, including feeding and gastrointestinal difficulties, high pain threshold and/or hypersensitivity to sound, and dysmorphic features, including mild facial abnormalities, strabismus, and small hands and feet (summary by Jansen et al., 2017). [from OMIM]

Neurodevelopmental disorder with impaired language, behavioral abnormalities, and dysmorphic facies (NEDLBF) is characterized by global developmental delay, speech delay, variably impaired intellectual development, behavioral abnormalities, and dysmorphic facial features. The phenotype and severity of the disorder is heterogeneous, ranging from borderline to severe. Brain imaging is usually normal. More variable additional features include early feeding difficulties, failure to thrive, short stature, mild visual impairment, hypotonia, seizures (particularly febrile), and distal skeletal defects of the hands and feet (Jia et al., 2022). [from OMIM]

Over-sensitivity to certain frequency ranges of sound. [from HPO]