PMC6959155_01
(a and b) A1 aged 15 years. Facial profile demonstrating prominent forehead, high anterior hairline, and pointed chin.
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On examination she had a pointed chin (see Figure 1(a)) with small ears and a high anterior hairline. Her forehead was prominent (also present in her mother) as seen in Figures 1(a)and1(b).
(a and b) A1 with her maternal half-brother, B1. Note significant short stature (both <0.4th centile). A1 has lumbar lordosis.
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He is taller than A1 as shown in Figures 2(a) and 2(b) Human GH was administered from age 14 to 17 years under the SGA license (35 mug/kg daily) but with poor response.
(a and b) B1 (aged 21 years) facial front view and profile. Note prominent forehead and high anterior hairline.
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On examination he had a prominent forehead (although less than A1) (as seen in Figures 3(a) and 3(b), high anterior hairline, small hands, and feet, but nil else of particular note.
(a and b) Radiographs of A1's left hand and left forearm with changes described in the text.
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The skeletal survey performed aged 13 years showed subjective hypoplasia of the distal radial epiphyses (Figures 4(a) and 4(b)). The 4th and 5th metacarpals were bilaterally short (Figure 4(a)).
(a and b) B1 radiograph of right hand aged 15 years (a). B1 radiograph of right hand aged 3 years (b).
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B1's radiographs (hand and lower limb images) showed slight global bone age delay (age 6 years) and subjective smaller epiphyses (Figures 5(a) and 5(b)), with slight elongation of the fibula (Figure 6).
B1 radiograph of right lower limb (lateral and AP) aged 5 years.
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B1's radiographs (hand and lower limb images) showed slight global bone age delay (age 6 years) and subjective smaller epiphyses (Figures 5(a) and 5(b)), with slight elongation of the fibula (Figure 6).
Sanger sequence analysis for A1, B1, and their mother showing nucleotide change C>A, heterozygous.
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A heterozygous maternally inherited variant in the CDKN1C gene was identified; c.836G>T; p.(Arg279Leu) (NM_000076.2) as shown in Figure 7.
Focussed pedigree showing CDKN1C gene change; c.836G>T; p.(Arg279Leu) in A1, B1, and their mother.
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This was confirmed by Sanger sequencing in the local diagnostic lab (West Midlands Regional Genetics Laboratory) and confirmed in her mother and B1 (as illustrated in Figure 8).