Monogenic nephrotic syndrome (NS) is associated with a resistance to initial glucocorticoid therapy and causative variants, which may be found in several genes influencing podocyte stability and kidney development. The TTC21B gene, which encodes the retrograde intraflagellar transport protein IFT139, is found mostly in association with ciliopathies in humans. The role of this protein in podocyte cytoskeleton stability was confirmed later and the mutated TTC21B also may be associated with proteinuric diseases, such as nephrotic syndrome. Our patient manifested as an infant with brachydactyly, nephrotic-range proteinuria, and renal tubular acidosis, and a kidney biopsy revealed focal segmental glomerulosclerosis (FSGS). Multiple phalangeal cone-shaped epiphyses of the hand were seen on X-ray. Next-generation sequencing revealed the well-described p.Pro209Leu heterozygous variant and a novel heterozygous p.Cys14Arg variant in the TTC21B gene. Our finding confirmed that the causative variants in the TTC21B gene may contribute to a spectrum of clinical features, such as glomerular proteinuric disease with tubulointerstitial involvement and skeletal abnormalities.

BACKGROUND: Ellis-van Creveld (EVC) syndrome is one of the rarest ciliopathy syndromes. It is caused by mutations of the EVC and EVC2 genes which encode the EVC proteins present in the basal body of the primary cilium.
METHODS: We report on a Saudi family with two affected children. Gene analysis revealed a homozygous c.2T >A in exon 1 of the EVC gene. The most interesting finding in our patients was the wide - spread cone-shaped epiphyses in the hands and feet.
CONCLUSIONS: Although cone-shaped epiphyses is a known feature of EVC syndrome, it usually limited to the middle or proximal phalanges. The wide-spread cone-shaped epiphyses seen in our patients have not been previously reported.
CONCLUSIONS: EVC syndrome is very rare in the Middle East. We report on the first Saudi family with EVC syndrome confirmed by gene analysis. The most unique finding in our patients was the wide-spread cone-shaped epiphyses in the hands and feet. The abnormality is probably related to abnormal Indian hedgehog signaling in the primary cilium.

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Brachydactyly is a common feature of pseudohypoparathyroidism (PHP) type Ia. We studied the longitudinal growth of the short bones in the hand of a 15-yr-old girl with PHP type Ia who had been followed for congenital hypothyroidism. Radiographs of the hand of the patient, who had been X-rayed every year since 2 yr of age, were studied. She showed cone-shaped epiphyses of the hand at 2 yr of age before showing brachydactyly. At 4 yr of age, she showed brachydactyly and an advanced bone age, and some short bones were prematurely fused at 6 yr of age. The short bones without cone-shaped epiphyses were also short as a result of a disturbance of the longitudinal bone elongation. In conclusion, the brachydactyly of PHP type Ia is thus considered to be caused by both early epiphyseal fusion with cone-shaped epiphyses and a disturbance of the longitudinal bone elongation.

Trichorhinophalangeal syndrome is a very rare genetic disorder, where damage and mutation to the number 8 chromosome affects sufferers in numerous ways. The syndrome has three types, all characterized by abnormally short stature, sparse hair, short deformed fingers with cone-shaped epiphyses visible in radiographs. Type I is the most common. Type II is characterized by the development of multiple bony exostoses and frequently, mental disability. Type III is a more severe form of type I and is associated with short stature. This report presents a 28-year-old man who had the characteristic features of type I with the presence of multiple erupted supernumerary teeth with normal mentation and karyotyping with high resolution G banding displayed normal chromosomal complements.