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Identification of STAC3 variants in non‐Native American families with overlapping features of Carey–Fineman–Ziter syndrome and Moebius syndrome
Author(s) -
Telegrafi Aida,
Webb Bryn D.,
Robbins Sarah M.,
SpeckMartins Carlos E.,
FitzPatrick David,
Fleming Leah,
Redett Richard,
Dufke Andreas,
Houge Gunnar,
van Harssel Jeske J. T.,
Verloes Alain,
Robles Angela,
Manoli Irini,
Engle Elizabeth C.,
Jabs Ethylin W.,
Valle David,
Carey John,
HooverFong Julie E.,
Sobreira Nara L. M.
Publication year - 2017
Publication title -
american journal of medical genetics part a
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.064
H-Index - 112
eISSN - 1552-4833
pISSN - 1552-4825
DOI - 10.1002/ajmg.a.38375
Subject(s) - hypotonia , proband , kyphoscoliosis , facial weakness , ptosis , pediatrics , medicine , weakness , congenital myopathy , dermatology , genetics , anatomy , surgery , scoliosis , pathology , mutation , biology , biopsy , muscle biopsy , gene
Horstick et al. (2013) previously reported a homozygous p.Trp284Ser variant in STAC3 as the cause of Native American myopathy (NAM) in 5 Lumbee Native American families with congenital hypotonia and weakness, cleft palate, short stature, ptosis, kyphoscoliosis, talipes deformities, and susceptibility to malignant hyperthermia (MH). Here we present two non‐Native American families, who were found to have STAC3 pathogenic variants. The first proband and her affected older sister are from a consanguineous Qatari family with a suspected clinical diagnosis of Carey–Fineman–Ziter syndrome (CFZS) based on features of hypotonia, myopathic facies with generalized weakness, ptosis, normal extraocular movements, cleft palate, growth delay, and kyphoscoliosis. We identified the homozygous c.851G>C;p.Trp284Ser variant in STAC3 in both sisters. The second proband and his affected sister are from a non‐consanguineous, Puerto Rican family who was evaluated for a possible diagnosis of Moebius syndrome (MBS). His features included facial and generalized weakness, minimal limitation of horizontal gaze, cleft palate, and hypotonia, and he has a history of MH. The siblings were identified to be compound heterozygous for STAC3 variants c.851G>C;p.Trp284Ser and c.763_766delCTCT;p.Leu255IlefsX58. Given the phenotypic overlap of individuals with CFZS, MBS, and NAM, we screened STAC3 in 12 individuals diagnosed with CFZS and in 50 individuals diagnosed with MBS or a congenital facial weakness disorder. We did not identify any rare coding variants in STAC3 . NAM should be considered in patients presenting with facial and generalized weakness, normal or mildly abnormal extraocular movement, hypotonia, cleft palate, and scoliosis, particularly if there is a history of MH.