XCIND syndrome disorders and associated DNA-repair pathways. The prototype for the XCIND syndrome is A-T, involving X-ray sensitivity, Cancer susceptibility, Immunodeficiency, Neurologic involvement, and DSB repair.¹¹⁴  The NMR complex is necessary for recruitment of ATM to a DSB and activation of its kinase activity. Patients lacking NBS (nibrin), Mre11 (aka ATLD), and Rad50 proteins are usually children with features of XCIND syndrome, although the types of neurologic involvement differ for the 3 disorders.^119,123  Nonhomologous end-joining (NHEJ) repair comprises the major DSB repair pathway in man. Patients lacking functional proteins in this pathway often present in infancy as SCID, although DNA ligase IV deficiency has been described as well in children with primary dwarfism and in adults.^120,124  PNKP protein has both polynucleotide kinase and phosphatase functions, moving the phosphate groups from 5′ to 3′, thereby optimizing conditions for ligation in end-joining. PNKP may also play a role in single-strand break repair. Affected infants display intractable seizures, microcephaly, and developmental delay.¹²⁵  Absence of RNF168 protein results in poor retention of 53BP1 and BRCA1 at sites of DSB, as well as at other predicted interactions within the chromatin ubiquitin ligase cascade (CULC).¹¹⁷  Two patients with RNF168 have been described, both with adult-onset immunodeficiency, neurologic involvement, and growth retardation^116,117,126 ; severe microcephaly was noted in 1, with normal intelligence.¹¹⁶  The inclusion of Fanconi anemia (itself a syndrome) within this partial list of XCIND syndrome-associated disorders is based arguably on the manifestations of radiosensitivity,¹²⁷  and many of the patients have also been associated with untoward responses to chemotherapy.¹¹⁴  The disorders listed herein are inherited as autosomal recessives.