FamilyLabel R07-429

Family#PresentingHPOs HP:0001263, HP:0003072, HP:0003015, HP:0003300, HP:0000978, HP:0002099, HP:0003193, HP:0002721, HP:0002007, HP:0000316, HP:0000218, HP:0000767, HP:0008905, HP:0003027, HP:0002987, HP:0003049, HP:0001156, HP:0004209, HP:0006380, HP:0006460, HP:0002694, HP:0005930, HP:0011844, HP:0008788, HP:0003155, HP:0002850

(GDD, Hypercalcemia, Flared metaphyses, Ovoid vertebral bodies, Easy bruising, Asthma, Allergic rhinitis, Immunodeficiency, Frontal bossing, Hypertelorism, High arched palate, Pectus excavatum, Rhizomelia, Mesomelia, Contractures of elbows, Ulnar deviation of the wrist, Brachydactyly, Fifth finger clinodactyly, Knee contractures, Increased laxity of ankles, Sclerosis of skull base, Epiphyseal abnormality, Abnormal appendicular skeleton morphology, Delayed pubic bone ossification, elevated alkaline phosphatase, decreased IgM)

HPOsFreeText Born at term, significant developmental delay/special education, abnormal brain MRI, severe unclassified immunodeficiency, normal PTH concentration, mild hypercalcemia. Radiographic findings: widened/flared metaphyses with irregular ossification, moth-eaten long bones, fragmentation of the proximal metacarpals, and a distinctive transverse gap seen in the tibias. From table: eczema or atrophoderma, wheel chair bound-unable to bear weight on lower extremities, flattened supraorbital ridges, normal formed and positioned ears, mild pectus excavatum, Mesomelia with significant anterior bowing in the upper and lower extremities, Ulnar deviation at the wrists with laxity, telescoping fingers, Mild knee contractures, Significant laxity at the ankles with positional equinovarus, 2-3 syndactyly, Delayed ossification of the fontanel, Delayed ossification of the basal occipital bone, Delayed ossification of the posterior elements of the spine, Significant metaphyseal irregularities, Epiphyseal delay with irregular epiphyses, Subjectively large distance from the epiphyses to the metaphyseal edge, Ossification defect or gaps in the appendicular skeleton, Brachydactyly with metaphyseal irregularities and epiphyseal delay, IgE <1 (normal <20 IU/ml), CD3 T-lymphocytes 82% (normal 60-76%), Parathyroid hormone intact 19 (normal 11-51 pg/ml). Radiograph additionally showed widened/flared metaphyses with irregular ossifications and irregular ossification front, brachydactyly with irregular metacarpal and phalangeal metaphyses and delayed epiphyseal ossification, absence of pubic bone ossification, and delayed ossification of the basal occipital bone and subjectively increased density of the skull.

FamilyNotHPOs n/a

NotHPOsFreeText fixed equinovarus, walked with or without assistance

CountryOrigin n/a

Ethnicity n/a

Race n/a

Family#PreviousTesting PTH1R coding exons sequenced due to phenotype overlap with JMC. No variants identified.

ProbandLabel R07-429A

Variant NM_025164.4(SIK3):c.559C>T (p.Arg187Cys)

ClinVar 587366

gnomAD not in gnomAD

FamilyAddInfo consanguineous

FamilyPMIDs n/a

FamilyLabel R07-429

Family#PresentingHPOs HP:0001263, HP:0003072, HP:0003015, HP:0003300, HP:0000978, HP:0002099, HP:0003193, HP:0002721, HP:0002007, HP:0000316, HP:0000218, HP:0000767, HP:0008905, HP:0003027, HP:0002987, HP:0003049, HP:0001156, HP:0004209, HP:0006380, HP:0006460, HP:0002694, HP:0005930, HP:0011844, HP:0008788, HP:0003155, HP:0002850

(GDD, Hypercalcemia, Flared metaphyses, Ovoid vertebral bodies, Easy bruising, Asthma, Allergic rhinitis, Immunodeficiency, Frontal bossing, Hypertelorism, High arched palate, Pectus excavatum, Rhizomelia, Mesomelia, Contractures of elbows, Ulnar deviation of the wrist, Brachydactyly, Fifth finger clinodactyly, Knee contractures, Increased laxity of ankles, Sclerosis of skull base, Epiphyseal abnormality, Abnormal appendicular skeleton morphology, Delayed pubic bone ossification, elevated alkaline phosphatase, decreased IgM)

HPOsFreeText Born at term, significant developmental delay/special education, abnormal brain MRI, severe unclassified immunodeficiency, normal PTH concentration, mild hypercalcemia. Radiographic findings: widened/flared metaphyses with irregular ossification, moth-eaten long bones, fragmentation of the proximal metacarpals, and a distinctive transverse gap seen in the tibias. From table: eczema or atrophoderma, wheel chair bound-unable to bear weight on lower extremities, flattened supraorbital ridges, normal formed and positioned ears, mild pectus excavatum, Mesomelia with significant anterior bowing in the upper and lower extremities, Ulnar deviation at the wrists with laxity, telescoping fingers, Mild knee contractures, Significant laxity at the ankles with positional equinovarus, 2-3 syndactyly, Delayed ossification of the fontanel, Delayed ossification of the basal occipital bone, Delayed ossification of the posterior elements of the spine, Significant metaphyseal irregularities, Epiphyseal delay with irregular epiphyses, Subjectively large distance from the epiphyses to the metaphyseal edge, Ossification defect or gaps in the appendicular skeleton, Brachydactyly with metaphyseal irregularities and epiphyseal delay, IgE <1 (normal <20 IU/ml), CD3 T-lymphocytes 82% (normal 60-76%), Parathyroid hormone intact 19 (normal 11-51 pg/ml). Radiograph additionally showed widened/flared metaphyses with irregular ossifications and irregular ossification front, brachydactyly with irregular metacarpal and phalangeal metaphyses and delayed epiphyseal ossification, absence of pubic bone ossification, and delayed ossification of the basal occipital bone and subjectively increased density of the skull.

FamilyNotHPOs n/a

NotHPOsFreeText fixed equinovarus, walked with or without assistance

CountryOrigin n/a

Ethnicity n/a

Race n/a

Family#PreviousTesting PTH1R coding exons sequenced due to phenotype overlap with JMC. No variants identified.

ProbandLabel R07-429A

Variant NM_025164.4(SIK3):c.559C>T (p.Arg187Cys)

ClinVar 587366

gnomAD not in gnomAD

FamilyAddInfo consanguineous

FamilyPMIDs n/a