-Related Disorder

CLINICAL CHARACTERISTICS

-related disorder (-RD) constitutes a clinical continuum, from classic Coffin-Siris syndrome to intellectual disability with or without nonspecific dysmorphic features. Coffin-Siris syndrome is classically characterized by aplasia or hypoplasia of the distal phalanx or nail of the fifth and additional digits, developmental or cognitive delay of varying degree, distinctive facial features, hypotonia, hypertrichosis, and sparse scalp hair. Frequencies of other features, such as developmental delay (with speech often more affected than motor development), is consistent across the clinical spectrum, and may include malformations of the cardiac, gastrointestinal, genitourinary, and/or central nervous systems. Other findings seen in individuals with -RD include feeding difficulties, slow growth, ophthalmologic abnormalities, hearing impairment, seizures, attention-deficit/hyperactivity disorder, and autistic features.

DIAGNOSIS/TESTING: The diagnosis of RD is established by identification of a heterozygous pathogenic variant in by molecular genetic testing.

MANAGEMENT

Standard treatment for strabismus, refractive error, hearing loss, congenital heart defects, obstructive sleep apnea, constipation, gastroesophageal reflux, cryptorchidism, scoliosis, and seizure disorders. For significant feeding issues, a nasogastric and/or gastrostomy tube may be required. Developmental therapies, including speech/language and feeding therapy, is recommended for those with developmental delay. At least annual assessment of developmental progress and educational needs; annual ophthalmology evaluation and assessment for scoliosis (until growth is complete). Audiology evaluation, behavior assessment, and hormonal evaluation/bone age as needed based on symptoms. Those with seizures should be monitored as clinically indicated.

GENETIC COUNSELING

-related disorder is inherited in an autosomal dominant fashion. With the exception of two families in which a parent and child had features consistent with -related disorder, all individuals diagnosed to date have the disorder as the result of a pathogenic variant. Once the pathogenic variant has been identified in an affected family member, prenatal and preimplantation genetic testing are possible.