VACTERL with hydrocephalus (VACTERL-H) is a rare genetic disorder that affects multiple anatomical systems. Affected children typically present with a variety of conGenital anomalies at birth, however, in some children core features of the disorder are not noted until later in life. The combination of conGenital anomalies and the related symptoms may vary considerably in different affected individuals.
Hydrocephalus is a condition in which excessive accumulation of cerebrospinal fluid causes increased pressure on the tissues of the brain. In infants and young children this finding may be associated with an abnormally enlarged head size (macrocephaly). Symptoms of acute hydrocephalus typically include vomiting, irritability, seizures, and in severe cases downward deviation of the eyes and eventually, if untreated, coma and death. Other important signs may include Developmental delays evidenced by failure to achieve age appropriate developmental milestones and/or declining cognitive performance over time.
VACTERL-H is clinically defined and typically at least three of the eight anatomical components of the disorder are considered necessary for diagnosis. Importantly, there must be no laboratory or clinical evidence of an alternative diagnosis. The defining features of the disorder are discussed individually below.
Vertebral Anomalies Vertebral anomalies typically include segmentation defects of the bones that comprise the spinal column. They are frequently associated with rib anomalies although this is not always the case. Commonly reported vertebral anomalies include hemivertebrae, “butterfly vertebrae,” and “wedge vertebrae” in which the bones of the spinal column have an abnormal shape or architecture. Additionally, vertebral fusions and supernumerary vertebrae have been described. These changes can result in the spine having an abnormal curvature, or scoliosis, which in some patients is the first sign that an underlying vertebral anomaly may be present.
Anal Atresia Imperforate anus/anal atresia is a malformation in which the anal opening or the passage that normally connects the anus and the lowest part of the large intestine (rectum) fails to develop. This condition prevents the normal passage of bowel contents and typically results in obstruction of bowel contents. While complete imperforate anus is typically noticed on the initial post-natal examination performed at birth, other less severe forms of stenosis or atresia may present later with signs and symptoms of intestinal obstruction. Signs and symptoms of anal atresia may include persistent Nausea and vomiting, intestinal Bloating and weight loss due to difficulties with feeding.
Cardiac Defects A wide range of congenital Heart defects have been reported in children with VACTERL-H. The normal heart has four chambers. The two upper chambers, known as atria, are separated from each other by a fibrous partition known as the atrial septum. The two lower chambers are known as ventricles and are separated from each other by the ventricular septum. Valves connect the atria (left and right) to their respective ventricles. The aorta, the main vessel of arterial circulation, carries blood away from the left ventricle to the rest of the body.
A ventricular septal defect (VSD) is caused by a hole or small perforation anywhere along the ventricular septum and can present with a variety of symptoms depending on the size and the location of the defect. A small ventricular septal defect may close on its own, however larger defects may affect the ability of the heart to pump blood efficiently to the lungs and the rest of the body and result in congestive heart failure. Signs and symptoms associated with Heart failure may include increased respiratory rate (tachypnea), wheezing, increased heartrate (tachycardia), and growth delay in infants (failure to thrive).
Additional congenital Heart defects associated with VACTERL-H include atrial septal defects (ASDs); hypoplastic left heart syndrome (a life-treating condition in which there is underdevelopment of the left ventricle, the aortic and/or mitral valve, and the ascending aorta); a complex heart defect referred to as tetralogy of Fallot; transposition of the great arteries (a condition in which the aortic and pulmonary arteries are transposed); and patent ductus arteriosus [a condition in which the passage between the blood vessel that leads to the lungs (pulmonary arteries) and the major artery of the body (aorta) fails to close after birth]. (For more information on these conditions, choose the name of the disease as your search term in the Rare Disease Database.)
Tracheoesophageal Fistula and/or Esophageal Atresia A tracheoesophageal fistula is an abnormal connection between the trachea and the esophagus. This abnormal connection often leads to feeding problems and Respiratory infections as a result of food being passed to the lungs inappropriately.
Esophageal atresia is a condition in which the esophagus, which normally carries food from the mouth to the stomach, is narrowed or incompletely formed. This results in inability of contents of the esophagus such as food to pass to the stomach and intestines to be digested.
Renal/Genitourinary Anomalies A variety of abnormalities affecting the kidneys and urinary tract have been described in VACTERL-H. These include but are not limited to: lack of development of one or both kidneys (renal aplasia), malformation of one or both kidneys (renal dysplasia), displaced or malpositioned kidneys (renal ectopia), and abnormal backflow (reflux) of urine into the tube (ureter) that carries urine to the bladder (vesicoureteral reflux), and abnormal positioning of the urethral opening at the end of the penis (hypospadias). The presence of a renal or genitourinary anomaly can sometimes result in abnormal accumulation of urine in the kidneys (hydronephrosis) and/or frequent urinary tract infections.
Limb Anomalies Classically, anomalies of the forearm or thumb side of the forearm (radial side) have been reported in children with VACTERL-H. These include failure of the radius to grow (radial aplasia), underdevelopment of the radius (radial hypoplasia), underdevelopment or absence of the thumb and/or the presence of an extra bone in the thumb (triphalangeal tumb). However, other anomalies such as presence of extra digits (polydactyly) or missing digits (oligodactyly) of the hands, webbing of the fingers (syndactyly), and/or abnormal fusion of the two forearm bones (radioulnar synostosis) have also been described.
Additionally, while not considered a core feature of VACTERL-H, the presence of a single umbilical artery (which is a vessel important for proper transport of blood and deoxygenated blood away from the fetus) is commonly reported. This finding, if present on prenatal ultrasound is important to identify as it may be the first sign an underlying disorder may be present and should prompt additional imaging testing to search for other anomalies associated with VACTERL-H.
Prognosis With the improvement of medical and surgical care, the long-term prognosis of patients with VACTERL-H has improved. However, even with early diagnosis and improvements in care, affected individuals often experience a number of medical complications as a result of the presence of specific congenital anomalies. Vertebral malformations often result in chronic back pain, anal atresia often results in incontinence and/or chronic constipation, gastro-esophageal Reflux can be a consequence of tracheoesophageal fistulas, and renal anomalies are often associated with increased frequency of urinary tract infections (UTI) and the occurrence of renal stones (nephrolithiasis).