Neurodevelopmental disorder with dysmorphic facies and distal limb anomalies syndrome due to disruption of BPTF in a 35‐year‐old man initially diagnosed with Silver‐Russell syndrome

Phenotypic expansion of the BPTF‐related neurodevelopmental disorder with dysmorphic facies and distal limb anomalies

“…Unique exonic variants include nine frameshift, four nonsense, three splicing, two in‐frame deletions, one missense, and one single exon truncating deletion (Tables 1 and S1). We also describe one previously published chromosomal translocation and CNV deletion disrupting BPTF (Patient 22) (Midro et al, 1993; Midro et al, 2019). Variants were interpreted as pathogenic (11), likely pathogenic (7), or VUS (2) based on the current ACMG criteria.…”

“…We describe 26 individuals from 21 families, including four cases of familial or inherited variants, including one (Patient 22) previously reported (Midro et al, 1993, 2019). Patient 1 inherited her variant from her mother (Patient 2), Patient 9 was found to have inherited his variant from his mother (Patient 10), Patient 13 is the father of Patient 12, and Patient 16 is the mother of Patient 15.…”

“…(a) Patient 1, (b) Patient 2, (c) Patient 5, (d) Patient 12, (e) Patient 17, (f) Patient 18, (g) Patient 19, (h) Patient 20, (i) Patient 21 at age 9 years 10 months, (j) Patient 21 at age 10 years 3 months, (k) Patient 22 at age 8 years(Midro et al, 1993), (l) Patient 22 at age 35 years (Midro et al, 2019), (m) Patient 23, (n) Subject 5 from Stankiewicz et al, 2017 (Stankiewicz et al, 2017). Note the presence of prominent nasal ridge (a, b, c, e, g, h, i, k, l, n), bulbous nasal tip (a, d, h, k, m, n), and pointed chin (a, c, d, e, f, i, k, m, n) [Color figure can be viewed at wileyonlinelibrary.com]…”

“…The syndrome consists primarily of developmental delay (DD)/intellectual disability (ID), speech delay, postnatal microcephaly, and dysmorphic features. The disorder remains, however, incompletely differentiated with few further individuals described in the medical literature (Deciphering Developmental Disorders, 2015, 2017; Midro et al, 2019; Popp et al, 2017). All individuals identified thus far, have carried heterozygous de novo changes with mostly copy‐number variant (CNV) deletions and frameshift, or nonsense single‐nucleotide variants (SNVs).…”

Patterns of malformation associated with esophageal atresia/tracheoesophageal fistula: A retrospective single center study

“…It was predicted by in silico analysis to cause abnormal gene splicing. At an older age, the patient posteriorly underwent rapid whole genome sequencing which revealed the same variant, which was classified as pathogenic based on subsequent reports of a new phenotype associated with bromodomain PHD finger transcription factor (BPTF) (Midro et al, 2019; Stankiewicz et al, 2017). BPTF, a subunit of the NURF chromatin remodeling complex (Alkhatib & Landry, 2011), has been shown to have an important role in early embryonic tissue differentiation including the formation of mesoderm, endoderm and more differentiate ectoderm lineages (Landry et al, 2008).…”