TABLE 1.
Clinical features and molecular diagnosis for Patients 1–4
| Patient 1 | Patient 2 | Patient 3 | Patient 4 | |
|---|---|---|---|---|
| Gene | BBS1 | DYNC2H1 | BBS12 | WDR35 |
| RefSeq number | NM_024649.4 | NM_001080463.2 | NM_001178007.1 | NM_001006657.1 |
| cDNA | c.1169 T > G | c.7277G > T and c.7967G > A | c.695_731del37 | c.1633C > T and c.308G > T |
| Protein | p.(Met390Arg) | p.(Arg2426Leu) and p.(Arg2656His) | p.(Ile232Lysfsx3) | p.(Arg545*) and p.(Gly103Val) |
| Variant type | Homozygous missense | Compound heterozygous missense | Homozygous Frameshift | Compound heterozygous missense |
| Inheritance | Autosomal recessive | Autosomal recessive | Autosomal recessive | Autosomal recessive |
| Testing modality | Clinical exome sequencing | Research exome reanalysis | BBS gene panel | Research exome sequencing |
| Sex | Male | Male | Female | Male |
| Age at evaluation | 6 years | 30 months | 4 years 9 months | |
| Growth | Height and weight: 97% | Height and weight: 50% | Height 30%, weight > 99% | |
| Craniofacial | Sagittal craniosynostosis, dolichocephaly | Abnormal head shape as a neonate, self‐resolved | ||
| Eyes | Deep set and hooded eyes, no evidence of retinitis pigmentosa | Normal ophthalmology examination | No evidence of retinitis pigmentosa, astigmatism | Normal ophthalmology examination |
| Cardiac | Normal echocardiogram | Normal echocardiogram | ||
| Pulmonary | Negative | Negative | Negative | Recurrent otitis media, no pulmonary findings |
| GI | Normal liver ultrasound and aminotransferases | Ductal plate malformation, cirrhosis, portal hypertension | Imperforate anus | Ductal plate malformation, cirrhosis, portal hypertension |
| GU | Increased renal echogenicity and right sided renal cysts | Normal renal ultrasounds | Bilateral cystic renal dysplasia, vesicoureteral reflux | Abnormal renal echogenicity, hypertension |
| Endocrine | Hyperphagia, dyslipidemia | Obesity, normal hemoglobin A1c | ||
| Skeletal | Bilateral lower extremity polydactyly | Normal chest xray, chest circumference 50% | Bilateral lower extremity polydactyly | Normal skeletal survey |
| Skin and joints | No ectodermal findings, hypermobility | No ectodermal findings | No ectodermal findings | No ectodermal findings |
| Development | Mild global developmental delay | Normal | Mild global developmental delay | Mild global developmental delay |