ABSTRACT
MTSS2-related neurodevelopmental disorder (MTSS2-related NDD) (MIM 620086) is characterized by intellectual developmental disorder with ocular anomalies and distinctive facial features (IDDOF). The only existing report to date described five individuals who exhibited an identical de novo c.2011C>T (p.Arg671Trp) variant in the MTSS2 gene. Herein, we report a new case of MTSS2-related NND in a male dizygotic twin who presented with IDDOF and severe intellectual disability. This patient also displayed additional clinical features, including low functioning autism, hypothyroidism, duodenal obstruction secondary to Ladd's bands, inguinal hernias, cryptorchidism, transient subperiosteal new bone formation, and short stature with delayed bone age, which had not been previously reported in association with the MTSS2-related NDD. Exome sequencing identified the recurrent c.2011C>T (p.Arg671Trp) variant in the MTSS2 gene. The mother and the other twin tested negative for the pathogenic variant, while the father's participation in the study was unavailable. This case confirms that the MTSS2-related NDD is caused by the recurrent MTSS2 missense variant p.Arg671Trp. The novel findings identified in our patient expand the phenotypic spectrum associated with this new autosomal dominant entity, but further studies on its genetic and clinical manifestations are still needed.
Subject(s)
Autistic Disorder , Intellectual Disability , Neurodevelopmental Disorders , Humans , Male , Intellectual Disability/genetics , Intellectual Disability/pathology , Mutation, Missense , Neurodevelopmental Disorders/genetics , PhenotypeABSTRACT
Aneurysmal coronary artery disease (ACAD) has been reported rarely in patients with neurofibromatosis type 1 (NF1), mostly in adults. We report on a female newborn affected by NF1 with ACAD disclosed during investigation for an abnormal prenatal ultrasound along with a review of the previously reported cases. The proposita had multiple café-au-lait spots and had no cardiac symptoms. Echocardiography, and cardiac computed tomography angiography confirmed aneurysms on the left coronary artery, left anterior descending coronary artery, and of the sinus of Valsalva. Molecular analysis detected the pathogenic variant NM_001042492.3(NF1):c.3943C>T (p.Gln1315*). Literature findings on ACAD in NF1 indicated that this mostly occurs in males, showing predilection for the development of aneurysms at the left anterior descending coronary artery, and manifesting predominantly as acute myocardial infarction, inclusively in teenagers, though it may be also asymptomatic as in our case. This report documents the first case of ACAD in a patient with NF1 diagnosed at birth, emphasizing that its early diagnosis is essential to prevent potential life-threatening events attributable directly to coronary lesions.