17q12 recurrent (RCAD syndrome) region (includes HNF1B)

Mefford. GeneReviews article.

Kamath et al. (2017) described a three-generation family with 5 affected carriers of the recurrent 17q12 duplication. The proband was identified through routine clinical microarray testing and additional family members were tested by FISH. Clinical findings were variable amongst family members, but common phenotypes included renal problems, diabetes mellitus, learning difficulties, epilepsy, and neuropsychiatric disorders. The authors also reviewed and summarized the peer-reviewed literature as well as findings of over 100 patients with similar duplications in the DECIPHER clinical database.

Rasmussen et al. (2016) described a large Danish cohort of 26 total 17q12 duplication carriers from 13 families with a proband (index patient) identified through routine clinical microarray testing and family member studied by array or targeted molecular method. The most prevalent clinical findings across index patients were learning disabilities in 7/8 (88%), motor delays in 8/11 (73%), language delay in 7/10 (70%), and neurological or psychiatric problems in 6/13 (46%). Additional variable findings included structural brain anomalies in 2/9 (22%), kidney abnormalities in 2/8 (25%), eye abnormalities in 4/13 (31%) and joint laxity in 3/13 (23%). Three index patients had an additional finding by array and some were patients with variable findings. Non-index carriers had lower frequencies of assessment and presence of all phenotypes but most prevalent included learning disabilities in 4/12 (33%) and language delay in 2/11 (18%). Of the individuals for whom inheritance information was available, the duplication was inherited in 15/16 families and de novo in one. A review of clinical findings for 92 previously reported patients from the literature was also provided.

Mitchell et al. (2015) described clinical features of 30 unrelated patients and 2 affected siblings with 17q12 duplications, identified through routine clinical, and in some cases, research microarray testing. The most prevalent clinical findings across duplication carriers were developmental delays/intellectual disability (including speech delays), an inconsistent pattern of dysmorphic features, microcephaly, and seizures. Other features reported in a subset of patients included behavioral and psychiatric disorders, growth delays, and other anomalies. The duplication was inherited in 19/21 cases and de novo in 2/21 cases. Of the 14 parents for whom phenotypic information was available and the 17q12 duplication was the only finding on microarray testing, 8 were reported to be clinically affected. Features reported in these parents included learning disabilities, microcephaly, and seizures.