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Schinzel-Giedion syndrome (SGS) is an ectodermal dysplasia syndrome chiefly characterized by a distinctive facial dysmorphism, hydronephrosis, severe developmental delay, typical skeletal malformations, and genital and cardiac anomalies.
The birth prevalence of SGS is not known. More than 50 cases have been reported worldwide to date.
At birth, SGS is quite easily characterized by the distinctive facial dysmorphism with a prominent forehead, midface retraction resembling a broadened ''figure-of-eight'' in marked cases, and a short upturned nose, as well as visceral abnormalities and hypertrichosis. Hydronephrosis is present in nearly all affected cases (91%). Cardiac abnormalities, including septal defects, valvular dysplasias, hypoplastic ventricles and patent ductus arteriosus are common (43%), as are other genitourinary abnormalities (76%), such as cryptorchidism, micropenis, hypospadias, hypoplastic uterus, hypoplastic labia minora and majora, deep labial sulcus, and anteriorly displaced anus. Neonates frequently present with short limbs and the following limb malformations: valgus or varus foot deformity, mesomelic brachymelia with hypoplastic and hyperconvex nails and single palmar creases of the hands. Affected neonates suffer from hypotonia and typically present with respiratory failure, with all having a severe developmental delay accompanied by seizures (often refractory), and visual and hearing impairment. Additionally, a higher than normal prevalence for neuroepithelial tumors (17%) in SGS patients has been reported.
SGS is caused by de novo mutations in the SETBP1 gene (18q21.1), probably resulting in a gain-of-function or dominant-negative effect.
Diagnosis is based on clinical findings (including the distinctive facial dysmorphism), the presence of hydronephrosis on ultrasound, and radiographic findings of multiple typical skeletal malformations including sclerotic skull base, wide occipital synchondrosis, increased cortical thickness/density and broad ribs. Under 12 months of age, skull radiographs reveal a gap between the 2 parts of the occipital bone and dense pyramids are also common. Genetic testing for SETBP1 is possible.
Other conditions with the distinctive midface retraction that could be considered in the differential diagnosis include fetal hydantoin, fetal warfarin syndromes, Zellweger syndrome, mucopolysaccharidosis, gangliosidosis, and rhizomelic chondrodysplasia punctata, as well as congenital hypothyroidism (see these terms).
Hydronephrosis is detectable on prenatal ultrasound between the 18th-37th week of pregnancy, in about 40% of affected cases. Genetic testing is possible.
SGS is an autosomal dominant disorder. Practically all cases occur sporadically, identification of the proband should be undertaken along with genetic counseling for parents.
Management and treatment
Management is supportive and consists of palliative care. The chief complications are respiratory failure, feeding intolerance, refractory seizures and frequent and recurrent infections such as pneumonia.
Prognosis is severe, with most affected patients not surviving infancy due to the progressive neurodegeneration, increased risk of tumors, recurrent infections and respiratory failure, although survival until adolescence has been reported.