Tsurusaki et al. (2012) identified SMARCB1 mutations in 4 individuals with a multiple congenital anomaly/mental retardation syndrome classified by them as Coffin-Siris syndrome (135900). All had developmental delay and hypotonia; 2 of 3 examined had microcephaly, 2 of ... Tsurusaki et al. (2012) identified SMARCB1 mutations in 4 individuals with a multiple congenital anomaly/mental retardation syndrome classified by them as Coffin-Siris syndrome (135900). All had developmental delay and hypotonia; 2 of 3 examined had microcephaly, 2 of 3 had a small cerebellum; 2 of the 4 had seizures, and neither of 2 examined had Dandy-Walker malformation. Three of the 4 had hearing loss. All 4 had absent or hypoplastic fifth finger or toenails, sparse scalp hair, thick eyebrows, and long eyelashes. Three of 3 examined had abnormal delayed dentition, 2 of 3 had nonfunctioning or absent tear duct, and 3 of the 4 were hirsute. All 4 were described as having a coarse facial appearance with broad nose, wide mouth, thick lips, abnormal ears, and a high palate. All 4 had short stature, 3 of the 4 had spinal anomalies, and all had feeding problems. Absent hypoplastic fifth phalanx of the hand and the foot and delayed bone age were found in 1 patient examined for these. Other phenotypic features were more variable. Two patients for whom pictures were presented, while dysmorphic, did not resemble each other.
In patients with a syndromic form of mental retardation (MRD15), Tsurusaki et al. (2012) identified a missense mutation in the SMARCB1 gene in 1 patient (601607.0013) and the same single-codon deletion (601607.0012) in 3 patients. Germline heterozygous truncating ... In patients with a syndromic form of mental retardation (MRD15), Tsurusaki et al. (2012) identified a missense mutation in the SMARCB1 gene in 1 patient (601607.0013) and the same single-codon deletion (601607.0012) in 3 patients. Germline heterozygous truncating mutations in SMARCB1 have been reported in individuals with rhabdoid tumor predisposition syndrome-1 (609322), and various types of mutations in SMARCB1 have been reported in the germline of individuals with familial and sporadic schwannomatosis (162091). The SMARCB1 mutations resulting in MRD15 were nontruncating, implying that they exert gain-of-function or dominant-negative effects (excluding haploinsufficiency as a cause). In a patient with some features of Kleefstra syndrome (610253), Kleefstra et al. (2012) detected a missense mutation in the SMARCB1 gene (R37H; 601607.0014). The patient was 1 of 9 patients with syndromic mental retardation who shared core features of Kleefstra syndrome but were phenotypically heterogeneous otherwise, with a phenotype referred to by the authors as Kleefstra syndrome spectrum (KSS) .