Hypertelorism, and Situs inversus totalis

Right atrial isomerism is a severe complex congenital heart defect resulting from embryonic disruption of proper left-right axis determination. RAI is usually characterized by complete atrioventricular septal defect with a common atrium and univentricular AV connection, total anomalous pulmonary drainage, and transposition or malposition of the great arteries. Affected individuals present at birth with severe cardiac failure. Other associated abnormalities include bilateral trilobed lungs, midline liver, and asplenia, as well as situs inversus affecting other organs. Left atrial isomerism (LAI) is a related disorder with a somewhat better prognosis. LAI is characterized by bilateral superior vena cava, interruption of the intrahepatic portion of the inferior vena cava, partial anomalous pulmonary venous drainage, and ventricular septal defect. Patients with LAI may have polysplenia and bilateral bilobed lungs, as well as situs inversus affecting other organs. Both RAI and LAI malformation complexes have classically been referred to as Ivemark syndrome (summary by Eronen et al., 2004 and Kaasinen et al., 2010).

IVEMARK SYNDROME Is also known as ivemark syndrome|asplenia with cardiovascular anomalies|right isomerism

• Growth delay
• Hypertelorism
• Low-set ears
• Flexion contracture
• Intrauterine growth retardation

SOURCES: OMIM ORPHANET MENDELIAN

HeterotaxyHeterotaxy ('heter' meaning 'other' and 'taxy' meaning 'arrangement'), or situs ambiguus, is a developmental condition characterized by randomization of the placement of visceral organs, including the heart, lungs, liver, spleen, and stomach. The organs are oriented randomly with respect to the left-right axis and with respect to one another (Srivastava, 1997). Heterotaxy is a clinically and genetically heterogeneous disorder. Multiple Types of Congenital Heart DefectsCongenital heart defects (CHTD) are among the most common congenital defects, occurring with an incidence of 8/1,000 live births. The etiology of CHTD is complex, with contributions from environmental exposure, chromosomal abnormalities, and gene defects. Some patients with CHTD also have cardiac arrhythmias, which may be due to the anatomic defect itself or to surgical interventions (summary by van de Meerakker et al., 2011). ReviewsObler et al. (2008) reviewed published cases of double-outlet right ventricle and discussed etiology and associations. Genetic Heterogeneity of Visceral HeterotaxySee also HTX2 (OMIM ), caused by mutation in the CFC1 gene (OMIM ) on chromosome 2q21; HTX3 (OMIM ), which maps to chromosome 6q21; HTX4 (OMIM ), caused by mutation in the ACVR2B gene (OMIM ) on chromosome 3p22; HTX5 (OMIM ), caused by mutation in the NODAL gene (OMIM ) on chromosome 10q22; HTX6 (OMIM ), caused by mutation in the CCDC11 gene (OMIM ) on chromosome 18q21; HTX7 (OMIM ), caused by mutation in the MMP21 gene (OMIM ) on chromosome 10q26; and HTX8 (OMIM ), caused by mutation in the PKD1L1 gene (OMIM ) on chromosome 7p12. Genetic Heterogeneity of Multiple Types of Congenital Heart DefectsAn X-linked form of CHTD, CHTD1, is caused by mutation in the ZIC3 gene on chromosome Xq26. CHTD2 (OMIM ) is caused by mutation in the TAB2 gene (OMIM ) on chromosome 6q25. A form of nonsyndromic congenital heart defects associated with cardiac rhythm and conduction disturbances (CHTD3 ) has been mapped to chromosome 9q31. CHTD4 (OMIM ) is caused by mutation in the NR2F2 gene (OMIM ) on chromosome 15q26. CHTD5 (OMIM ) is caused by mutation in the GATA5 gene (OMIM ) on chromosome 20q13. CHTD6 (OMIM ) is caused by mutation in the GDF1 gene (OMIM ) on chromosome 19p13.

HETEROTAXY, VISCERAL, 1, X-LINKED; HTX1 Is also known as situs inversus, complex cardiac defects, and splenic defects, x-linked|laterality, x-linked|dextrocardia with other cardiac malformations

• Hypertelorism
• Failure to thrive
• Cleft palate
• Ventricular septal defect
• Atrial septal defect

SOURCES: MESH OMIM ORPHANET MENDELIAN

Meckel syndrome (MKS) is a rare, lethal, genetic, multiple congenital anomaly disorder characterized by the triad of brain malformation (mainly occipital encephalocele), large polycystic kidneys, and polydactyly, as well as associated abnormalities that may include cleft lip/palate, cardiac and genital anomalies, central nervous system (CNS) malformations, liver fibrosis, and bone dysplasia.

MECKEL SYNDROME Is also known as meckel-gruber syndrome

• Microcephaly
• Hypertelorism
• Micrognathia
• Cleft palate
• Cataract

SOURCES: ORPHANET MENDELIAN

RENAL-HEPATIC-PANCREATIC DYSPLASIA 1; RHPD1 Is also known as rhpd

• Growth delay
• Hypertelorism
• Flexion contracture
• Hepatomegaly
• Intrauterine growth retardation

SOURCES: OMIM MENDELIAN

Carpenter syndrome is a subtype of a family of genetic disorders known as acrocephalopolysyndactyly (ACPS) disorders.

CARPENTER SYNDROME Is also known as acrocephalopolysyndactyly type 2|acps2

• Intellectual disability
• Global developmental delay
• Hypertelorism
• Sensorineural hearing impairment
• Abnormal facial shape

SOURCES: ORPHANET OMIM MENDELIAN

The newly described 22q11.2 microduplication syndrome (dup22q11 syndrome) is the association of a broad clinical spectrum and a duplication of the region that is deleted in patients with DiGeorge or velocardiofacial syndrome (DG/VCFS; see this term), establishing a complementary duplication syndrome.

22Q11.2 MICRODUPLICATION SYNDROME Is also known as duplication 22q11.2|chromosome 22q11.2 microduplication syndrome|trisomy 22q11.2|dup(22)(q11)

• Intellectual disability
• Seizures
• Global developmental delay
• Short stature
• Generalized hypotonia

SOURCES: OMIM ORPHANET MESH MENDELIAN

Marden-Walker syndrome (MWS) is a malformation syndrome characterized by multiple joint contractures (arthrogryposis), a mask-like face with blepharophimosis, micrognathia, high-arched or cleft palate, low-set ears, decreased muscular bulk, kyphoscoliosis and arachnodactyly.

MARDEN-WALKER SYNDROME Is also known as mws

• Intellectual disability
• Seizures
• Global developmental delay
• Generalized hypotonia
• Microcephaly

SOURCES: ORPHANET MESH OMIM MENDELIAN

Restrictive dermopathy (RD) is a neonatal lethal genetic disease characterized by very tight and thin skin with erosions and scaling, associated to a typical facial dysmorphism, arthrogryposis multiplex, fetal akinesia or hypokinesia deformation sequence (FADS) (see these terms) and pulmonary hypoplasia without neurological abnormalities.

RESTRICTIVE DERMOPATHY Is also known as fetal hypokinesia sequence due to restrictive dermopathy|hyperkeratosis-contracture syndrome|lethal restrictive dermopathy|tight skin contracture syndrome, lethal|tight skin contracture syndrome

• Growth delay
• Hypertelorism
• Micrognathia
• Abnormal facial shape
• Low-set ears

SOURCES: ORPHANET MESH OMIM MENDELIAN

Catel-Manzke syndrome is a rare bone disease characterized by bilateral hyperphalangy and clinodactyly of the index finger typically in association with Pierre Robin sequence (see this term) comprising micrognathia, cleft palate and glossoptosis.

CATEL-MANZKE SYNDROME Is also known as index finger anomaly-pierre robin syndrome|index finger anomaly with pierre robin syndrome|pierre robin syndrome-hyperphalangy-clinodactyly syndrome|micrognathia digital syndrome|palatodigital syndrome, catel-manzke type|pierre robin syndrome with hyperph

• Seizures
• Global developmental delay
• Short stature
• Scoliosis
• Growth delay

SOURCES: ORPHANET OMIM MENDELIAN

Acrodysostosis-1 is a form of skeletal dysplasia characterized by short stature, severe brachydactyly, facial dysostosis, and nasal hypoplasia. Affected individuals often have advanced bone age and obesity. Laboratory studies show resistance to multiple hormones, including parathyroid, thyrotropin, calcitonin, growth hormone-releasing hormone, and gonadotropin (summary by Linglart et al., 2011). However, not all patients show endocrine abnormalities (Lee et al., 2012). Genetic Heterogeneity of AcrodysostosisSee also ACRDYS2 (OMIM ), caused by mutation in the PDE4D gene (OMIM ) on chromosome 5q12.

ACRODYSOSTOSIS 1 WITH OR WITHOUT HORMONE RESISTANCE; ACRDYS1 Is also known as adohr

• Intellectual disability
• Short stature
• Hearing impairment
• Scoliosis
• Hypertelorism

SOURCES: OMIM MENDELIAN