Case Presentation Case 1 A 38-year-old woman with HCS presented with severe cervical and upper thoracic back pain that had significantly worsened over the past six months. [cureus.com]

Furthermore, this disease presents a wide and specific clinical spectrum that is rare to encounter in full in a single patient. [encyclopedia.pub]

[…] decay and that the resulting truncated NOTCH2 proteins act in a gain-of-function manner. ...read moreread less Journal Article•DOI• TL;DR: Case reports of six affected individuals in two additional families and a summary of the English literature is presented [typeset.io]

These mutations produce symptoms that come and go, but have been present de novo. HCS-03 was identified as the variant that is passed through affected family members and presents symptoms throughout the lifetime of the individual. [en.wikipedia.org]

HCS is a rare bone disease with a defect in collagen and bone formation. [3], [6] It has an autosomal dominant inheritance [6] but sporadic cases have also been reported. [5] It presents at birth with dysmorphic features. [ijri.org]

• Short Stature

  Diagnosis Based on the clinical findings of short stature, hand pain, weakness, pathologic fractures, and distal osteolytic lesions. [accesspediatrics.mhmedical.com]

  Clinical examination revealed short stature, coarse features, bushy eyebrows, anti-Mongoloid slant [Figure - 1], flared anteverted nostrils, dental abnormalities, short stubby fingers, a wide short neck, genu valgus, and swollen feet with short toes. [ijri.org]

  Clinical features include: short stature; premature loss of dentition; short webbed neck pseudoclubbing; shortening of digits; pain in digits optical atrophy; optic disc edema hearing loss (conductive or sensorineural) frontal and occipital headaches [radiopaedia.org]

  Phenotype Short stature, coarse and dysmorphic facies, bowing of the long bones, vertebral anomalies Facial features include hypertelorism, bushy eyebrows, micrognathia, small mouth with dental anomalies, low-set ears, and short neck. [iofbonehealth.org]

• Premature Loss of Teeth

  loss of teeth, and short stature. [5] The clinical presentation, biochemical investigations, and typical radiological features aid in confirming the diagnosis. [ijri.org]

  Due to this is rare disease, we highlights the importance of presenting the first case reported in Colombia of a 20 years old patient with acroosteolysis, short stature, plantar ulcer, premature loss of teeth, and characteristic facies which has been [scielo.org.co]

  In addition to osteolysis of the distal phalanges, these patients have a generalized osseous dysplasla with osteoporosis, premature loss of teeth, short stature and a distinctive facial appearance. [typeset.io]

  These included (1) acroosteolysis, (2) wormian bones, (3) platypasia, (4) premature loss of teeth, (5) micrognathia, (6) coarse face, (7) coarse hair, (8) midface flattening, (9) short stature (<5%), and (10) a positive family history [5]. [hindawi.com]

• Hearing Impairment

  There was no history of any delay in eruption of teeth as well as no visual or hearing impairment. There was no similar history in the family. On examination, his height was 165 cm and body weight was 45 kg. [ncbi.nlm.nih.gov]

• Hirsutism

  the genitourinary tract (cystic kidney disease in 14% of patients), hypoplastic kidneys, glomerulonephritis, reflux nephropathy, hypogonadism), the abdomen (intestinal malrotation, umbilical and inguinal hernias, hepatosplenomegaly), and the skin (hirsutism [accessanesthesiology.mhmedical.com]

  Facial alterations: coarse and dysmorphic facies, elongated philtrum, micrognathia, low-set ears,telecanthus, sinofridia, bushy eyebrows, long eyelashes, wide nose, high arched palate, premature denture loss, jaw malocclusion, hirsutism, and hypertelorism [encyclopedia.pub]

  […] basilar invagination [11]), hydrocephalus [12] and syringomyelia [13]; facial alterations such as hypertelorism, sinofridia, thick hair, low-set ears, elongated philtrum, small jaw, high-arched palate, premature denture loss [14], unusually deep voice and hirsutism [mdpi.com]

• Short Nails

  Other alterations: delayed motor development, hearing loss, changes of the voice, deep voice, short nails, plantar ulcers, and hernias. The most relevant clinical manifestations are shown in figures 1, 2,3 and 4. Figure 1. [encyclopedia.pub]

• Short Neck

  Phenotype Short stature, coarse and dysmorphic facies, bowing of the long bones, vertebral anomalies Facial features include hypertelorism, bushy eyebrows, micrognathia, small mouth with dental anomalies, low-set ears, and short neck. [iofbonehealth.org]

  Musculoskeletal alterations: short stature, short neck, fractures of long bones, joint laxity, biconcave vertebrae, kyphoscoliosis, cervical instability, vertebral collapse, genu valgum, serpentine fibula, acroosteolysis, pseudoclubbing, short fingers [encyclopedia.pub]

  Clinical examination revealed short stature, coarse features, bushy eyebrows, anti-Mongoloid slant [Figure - 1], flared anteverted nostrils, dental abnormalities, short stubby fingers, a wide short neck, genu valgus, and swollen feet with short toes. [ijri.org]

  The following are noted: small face, telecanthus and downslated palpebral fissures, micrognathia, small mouth, thin lips, long philtrum and full cheeks, low-positioned ears with a crease in the lobules, short neck, and coarse hair. [pubmed.ncbi.nlm.nih.gov]

  Facial features include hypertelorism, bushy eyebrows, micrognathia, small mouth with dental anomalies, low-set ears, and short neck. There is progressive focal bone destruction, including acroosteolysis and generalized osteoporosis. [malacards.org]

• Coarse Face

  These included (1) acroosteolysis, (2) wormian bones, (3) platypasia, (4) premature loss of teeth, (5) micrognathia, (6) coarse face, (7) coarse hair, (8) midface flattening, (9) short stature (<5%), and (10) a positive family history [5]. [hindawi.com]

• Kidney Failure

  Renal alterations: hypospadias, cryptorchidism, renal cysts, and kidney failure. -Respiratory alterations: thoracic deformities, ventilatory restriction, and recurrent infections. [encyclopedia.pub]

Clinical Testing and Workup Common x-rays of the skull can reveal characteristic changes including open sutures and an abnormally flattened base of the skull. X-rays of the spine can show fractures and bone loss. [rarediseases.org]

Standard Therapies Treatment The treatment of Hajdu-Cheney syndrome is directed toward the specific symptoms that are apparent in each individual. Treatment may require the coordinated efforts of a team of specialists. [rarediseases.org]

treatment in relation to the age at which treatment was started (17 courses of treatment in 15 individuals). [ojrd.biomedcentral.com]

Our results support a potential therapeutic role for Notch pathways in treatment of osteoporosis. [typeset.io]

[…] aplasia of the frontal sinuses J-shaped enlarged sella dolichocephaly platybasia with or without basilar invagination Spine kyphoscoliosis spondylolisthesis biconcave vertebrae Maxillofacial hypoplastic maxilla malalignment of teeth wide mandibular angle Treatment [radiopaedia.org]

Sutton, Ameliaa,c; Morgan, Sarah L.d; Patry, Lysannee; Samuels, Mark E.e,f Departments of aGenetics bPediatrics cDepartment of Obstetrics and Gynecology, Division of Maternal Fetal Medicine dDepartment of Medicine, and UAB Osteoporosis Prevention and Treatment [journals.lww.com]

[…] frontal sinuses J-shaped enlarged sella dolichocephaly platybasia with or without basilar invagination Spine kyphoscoliosis spondylolisthesis biconcave vertebrae Maxillofacial hypoplastic maxilla malalignment of teeth wide mandibular angle Treatment and prognosis [radiopaedia.org]

Prognosis HCS is classified as a rare genetic disease but there are no studies that offer a global perspective on the prognosis and quality of life of afected patients. [encyclopedia.pub]

Hajdu-Cheney syndrome is a slowly progressive disease with a frequently unfavourable prognosis in elderly patients, especially for the development of dental anomalies, osteoporosis and the progression of skeletal complications requiring orthopedic surgeries [pubmed.ncbi.nlm.nih.gov]

The treatment of the disorder is symptomatic and the prognosis is quite good, with the morbidity depending on the bone changes caused by acro-osteolysis and the neurological complications caused by basilar invagination. [ijri.org]

(de Quervain’s thyroiditis), 6 Definition and epidemiology, 6 Etiology and pathogenesis, 6 Signs and symptoms, 6 Diagnosis, 6 Treatment, 6 Illustration (Fig. 1.7), 7 Benign thyroid nodules, 8 Definition and epidemiology, 8 Etiology and pathogenesis, [euro-libris.ro]

The acro-osteolysis has been variably attributed to either a vascular etiology [6] or defective development [4] leading to pseudo-osteolysis. [ijri.org]

Etiology As we have previously stated, HCS is a genetic disease caused by a heterozygotic mutation of NOTCH2.The NOTCH signaling pathway is constituted by a series of linked occurrences that are intimately related to skeletal development and homeostasis [encyclopedia.pub]

She was diagnosed with a mild–moderate intermittent cyclic neutropenia of an unknown etiology, although this was possibly idiopathic, autoimmune or drug-induced. 10. [mdpi.com]

(de Quervain’s thyroiditis), 6 Definition and epidemiology, 6 Etiology and pathogenesis, 6 Signs and symptoms, 6 Diagnosis, 6 Treatment, 6 Illustration (Fig. 1.7), 7 Benign thyroid nodules, 8 Definition and epidemiology, 8 Etiology and pathogenesis, [euro-libris.ro]

Epidemiology Hajdu–Cheney syndrome has a prevalence of less than 1 in 1,000,000 live births. Since 1948, approximately 50 cases have been described worldwide. [encyclopedia.pub]

Pathophysiology Unknown. The disorder probably results from defective development of bone rather than destruction of bone already formed. [accesspediatrics.mhmedical.com]

In addition to Wolff’s law, given the unclear pathophysiology of HCS, it is possible that hyperostosis in these areas of stress may be secondary to the underlying pathophysiology. [cureus.com]

[…] present with diverse severity in different members of the same pedigree, ranging from low BMD to multiple fragility fractures. 2) Antiresorptive therapy may be more rational than osteoanabolic therapy, since increased osteoclastogenesis is the primary pathophysiological [endocrine-abstracts.org]

Pathophysiology Once a mutation has occurred, normal skeletal development is afected, causing a series of skeletal anomalies. There is a bone density déficit that leads to generalized skeletal dysplasia. [encyclopedia.pub]

Diagnosis, 77 Treatment, 77 Illustrations (Figs 4.1–4.5), 77–79 Skin diseases associated with diabetes, 80 Definition, 80 Etiology, 80 Signs and symptoms, 80 Diagnosis, 80 Treatment, 80 Illustrations (Figs 4.6 & 4.7), 80–81 Diabetic foot, 81 Definition, 81 Pathophysiology [euro-libris.ro]

Prevention of osteoporosis, vitamin D and bisphosphonates may also have a role 6. History and etymology First described by Nicholas Hajdu (1908–1987), Hungarian-English radiologist in 1948 as cranioskeletal dysplasia and later in 1965, by William D. [radiopaedia.org]

Cole, Lauraa; Sutton, Ameliaa,c; Morgan, Sarah L.d; Patry, Lysannee; Samuels, Mark E.e,f Departments of aGenetics bPediatrics cDepartment of Obstetrics and Gynecology, Division of Maternal Fetal Medicine dDepartment of Medicine, and UAB Osteoporosis Prevention [journals.lww.com]

There was no evidence that acro-osteolysis was prevented. [ojrd.biomedcentral.com]

Some individuals have been treated with medications that prevent bone resorption in order to treat osteoporosis. Normally, bone gradually breaks down (bone resorption) and then reforms, a process called bone turnover. [rarediseases.org]