MedGen

Heart and brain malformation syndrome (HBMS) is a severe autosomal recessive multiple congenital anomaly syndrome characterized by profoundly delayed psychomotor development, dysmorphic facial features, microphthalmia, cardiac malformations, mainly septal defects, and brain malformations, including Dandy-Walker malformation (summary by Shaheen et al., 2016). Homozygous mutation in the SMG9 gene can also cause neurodevelopmental disorder with intention tremor, pyramidal signs, dyspraxia, and ocular anomalies (NEDITPDO; 619995), a less severe neurodevelopmental disorder. [from OMIM]

Koolen-de Vries syndrome (KdVS) is characterized by developmental delay / intellectual disability, neonatal/childhood hypotonia, dysmorphisms, congenital malformations, and behavioral features. Psychomotor developmental delay is noted in all individuals from an early age. The majority of individuals with KdVS function in the mild-to-moderate range of intellectual disability. Other findings include speech and language delay (100%), epilepsy (~33%), congenital heart defects (25%-50%), renal and urologic anomalies (25%-50%), and cryptorchidism (71% of males). Behavior in most is described as friendly, amiable, and cooperative. [from GeneReviews]

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. [from HPO]

Muscular hypotonia (abnormally low muscle tone) manifesting in the neonatal period. [from HPO]

A disease of the brain characterized by an enduring predisposition to generate epileptic seizures. [from SNOMEDCT_US]

Trichohepatoenteric syndrome (THES), generally considered to be a neonatal enteropathy, is characterized by intractable diarrhea (seen in almost all affected children), woolly hair (seen in all), intrauterine growth restriction, facial dysmorphism, and short stature. Additional findings include poorly characterized immunodeficiency, recurrent infections, skin abnormalities, and liver disease. Mild intellectual disability (ID) is seen in about 50% of affected individuals. Less common findings include congenital heart defects and platelet anomalies. To date 52 affected individuals have been reported. [from GeneReviews]

A chromosomal disorder consisting of the absence of a part of a chromosome. [from MONDO]

Although the spectrum of phenotypic expression in trichohepatoenteric syndrome (THES) is broad, the characteristic features include intrauterine growth retardation, woolly hair, facial dysmorphism, intractable diarrhea in infancy requiring total parenteral nutrition, and immunodepression. Hepatic involvement contributes to the poor prognosis of affected patients (summary by Fabre et al., 2007). Genetic Heterogeneity of Trichohepatoenteric Syndrome Trichohepatoenteric syndrome-2 (THES2; 614602) is caused by mutation in the SKIV2L gene (SKIC2; 600478) on chromosome 6p21. Reviews Bourgeois et al. (2018) analyzed a cohort of 96 patients with THES from 85 different families, drawing from published reports (37 patients) and their own recruitment (59 patients). Approximately two-thirds of the patients carried biallelic TTC37 mutations, and one-third had SKIVL2 mutations; in 8 (8.3%) of the patients, only 1 mutation could be identified. Intractable diarrhea was present in 100% of patients regardless of genotype, with hair abnormalities (woolly, brittle, easily removable) present in 90%. Facial dysmorphisms were observed in 84% of clinically described patients, comprising primarily large forehead, broad nasal root, and hypertelorism. Intrauterine growth retardation was frequent, seen in 70% of TTC37-mutated patients and 86% of SKIV2L-mutated patients; however, there was no significant difference in postnatal growth between the 2 groups. Liver disease was common, and more frequent in patients with mutation in SKIV2L (88%) than in TTC37 (51%); findings ranged from elevated liver enzymes and hepatomegaly to fibrosis and cirrhosis. Immunodeficiency was reported in about half of clinically explored patients, presenting as low immunoglobulin count or lack of antibody response to immunization. In addition, approximately 40% to 50% of patients exhibited dermatologic abnormalities, mostly cafe-au-lait spots located on the lower limbs. Overall, the authors noted that THES patients with mutation in either gene exhibit remarkably similar clinical signs, involving primarily the gastrointestinal tract, hair, and face, and are indistinguishable in clinical practice. However, a few differences emerged from analysis of the cohort, with SKIV2L-associated THES showing an earlier onset and/or greater severity, with more severe liver disease and significantly smaller height and weight at birth. [from OMIM]

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. [from HPO]

Failure to meet, or late achievement of developmental milestones. [from NCI]

An abnormal morphology (form) of the face or its components. [from HPO]

People with CCHD have one or more specific heart defects. The heart defects classified as CCHD include coarctation of the aorta, double-outlet right ventricle, D-transposition of the great arteries, Ebstein anomaly, hypoplastic left heart syndrome, interrupted aortic arch, pulmonary atresia with intact septum, single ventricle, total anomalous pulmonary venous connection, tetralogy of Fallot, tricuspid atresia, and truncus arteriosus.

Some people with treated CCHD have few related health problems later in life. However, long-term effects of CCHD can include delayed development and reduced stamina during exercise. Adults with these heart defects have an increased risk of abnormal heart rhythms, heart failure, sudden cardiac arrest, stroke, and premature death.

Although babies with CCHD may appear healthy for the first few hours or days of life, signs and symptoms soon become apparent. These can include an abnormal heart sound during a heartbeat (heart murmur), rapid breathing (tachypnea), low blood pressure (hypotension), low levels of oxygen in the blood (hypoxemia), and a blue or purple tint to the skin caused by a shortage of oxygen (cyanosis). If untreated, CCHD can lead to shock, coma, and death. However, most people with CCHD now survive past infancy due to improvements in early detection, diagnosis, and treatment.

Each of the heart defects associated with CCHD affects the flow of blood into, out of, or through the heart. Some of the heart defects involve structures within the heart itself, such as the two lower chambers of the heart (the ventricles) or the valves that control blood flow through the heart. Others affect the structure of the large blood vessels leading into and out of the heart (including the aorta and pulmonary artery). Still others involve a combination of these structural abnormalities.

Critical congenital heart disease (CCHD) is a term that refers to a group of serious heart defects that are present from birth. These abnormalities result from problems with the formation of one or more parts of the heart during the early stages of embryonic development. CCHD prevents the heart from pumping blood effectively or reduces the amount of oxygen in the blood. As a result, organs and tissues throughout the body do not receive enough oxygen, which can lead to organ damage and life-threatening complications. Individuals with CCHD usually require surgery soon after birth. [from MedlinePlus Genetics]

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. [from HPO]

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

Any structural anomaly of the heart. [from HPO]

A chromosomal abnormality in which there is an addition or loss of chromosomes within a set (e.g., 23 + 22 or 23 + 24). [from NCI]

The presence of any atypical form of expressive language. [from HPO]