HDR Syndrome

HDR is an acronym for hypoparathyroidism, deafness, and renal dysplasia. DiGeorge-like syndrome characterized by hypoparathyroidism, heart defects, immune deficiency, deafness, and renal malformations caused by a haplo-insufficiency of the zinc-finger transcription factor GATA3.

Baraka Syndrome; Nephrosis Nerve Deafness Hypoparathyroidism Syndrome.

Approximately 40 cases described in the literature worldwide.

Autosomal dominant disorder caused by mutations in the GATA3 gene on chromosome 10. Gene map location is 10p15.

The GATA3 gene is part of the family of zinc-finger transcription factors; it is involved in vertebrate embryonic development and in the development of the parathyroids, inner ear, and kidneys.

Diagnosis is based on clinical and laboratory stigmata, genetic testing, and family history.

The typical triad of HDR—sensorineural deafness, hypocalcemia and/or hypoparathyroidism, and nephropathy—is present in almost all patients. The manifestation of renal involvement is variable and may range from vesicoureteral reflux to kidney aplasia. Developmental delay, seizure disorder, and a high incidence of cerebral infarcts have been described. Mild dysmorphic features may be present and may include hypertelorism, flat nose, proptosis, high arched palate, micrognathia, and limb anomalies.

Clinical examination with emphasis on facial malformations and routine blood work, including complete blood count, electrolytes, calcium, glucose, and kidney function test are required. Hematologic or biochemical disturbances, especially hypocalcemia, must be corrected prior to anesthesia. A complete medical history and current medication, for example, antiseizure drugs with the potential for drug interactions with anesthetic agents, must be documented. Anxiolysis is particularly important with deafness and mental retardation.

Calcium levels should be monitored regularly during blood transfusions or albumin infusions and corrected if necessary. Tracheal extubation can be difficult in patients with severe mental retardation because of the presence of chronic lung disease from recurrent aspirations and reduced ability to cough. In these more severely affected patients, the potential for postoperative mechanical ventilation must be considered and intensive care admission planned ahead.

Negative inotropic effects of anesthetic agents and response to neuromuscular blockade might be enhanced in the presence of hypocalcemia. Drugs with predominantly renal elimination should be used with caution in the presence of impaired kidney function. Consider antibioprophylaxis because these patients have potentially severe impairment of immune function.

DiGeorge Syndrome: Developmental field defect with facial dysmorphism, congenital heart defect, hypocalcemia, hypoparathyroidism, thymus hypoplasia, and increased susceptibility to infections. The hallmarks include conotruncal absence or hypoplasia of thymus and parathyroid glands. Mostly caused by a microdeletion in chromosome 22q11.2.

Velocardiofacial Syndrome: Unusual face syndrome. Seems associated with a defect of chromosome 22 (deletion 22q11). The most common features are cleft palate, congenital heart defects (interrupted aortic arch, truncus arteriosus, tetralogy of Fallot with pulmonary atresia, absent pulmonary valve syndrome, simple tetralogy of Fallot, ventriculoseptal defect, and d-transposition of the great arteries), hypoparathyroidism, seizures, muscular hypotonia, short stature, and scoliosis. The incidence of velocardiofacial syndrome is 8% of all children born with cleft palate.

Conotruncal Anomaly Face Syndrome (Takao Syndrome): Overlaps with DiGeorge syndrome with the phenotypic spectrum of a deletion of chromosome 22q11. Presents with congenital heart defects (tetralogy of Fallot, transposition of the great arteries, double-outlet right ventricle, ventriculoseptal defect), microstomia, cleft palate, mental retardation, strabismus, hypertelorism.