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Coffin–Siris syndrome (CSS; MIM 135900) is a multisystem congenital anomaly syndrome caused by mutations in the genes in the Brg‐1 associated factors (BAF) complex. Classically, individuals with CSS have been described with hypo‐ or aplasia of the fifth digit nails or phalanges (hence the term "fifth digit syndrome"). Other physical features seen include growth restriction, coarse facial features, hypertrichosis or hirsutism, sparse scalp hair, dental anomalies, and other organ‐system abnormalities. Varying degrees of developmental and intellectual delay are universal. To date, approximately 200 individuals have been described in the literature. With the advent of large‐scale genetic testing such as whole‐exome sequencing is becoming more available, more individuals are being found to have mutations in this pathway, and the phenotypic spectrum appears to be broadening. We report here a large cohort of 81 individuals with the diagnosis of CSS from the first parent‐reported CSS/BAF complex registry in an effort to describe this variation among individuals, the natural history of the syndrome, and draw some gene–phenotype correlations. We propose that changes in the BAF complex may represent a spectrum of disorders, including both ARID1B‐related nonsyndromic intellectual disability (ARID1B‐ID) and CSS with classic physical features. In addition, we offer surveillance and management recommendations based on the medical issues encountered in this cohort to help guide physicians and patients' families. [ABSTRACT FROM AUTHOR]

Key Clinical Message: Congenital Methemoglobinemia is a rare neurologic condition which can mimic other diseases such as epilepsy syndromes and leukodystrophies. The responsible gene, CYB5R3, is not typically included on commonly order neurologic and epilepsy panels. We recommend that laboratories include this gene on these tests which often precede larger‐scale genetic studies. [ABSTRACT FROM AUTHOR]