Primary Hyperparathyroidism Superimposed on a Pre-existing Familial Hypocalciuric Hypercalcemia Diagnosis

Familial hypocalciuric hypercalcemia is a rare clinical condition of persistently elevated serum calcium and reduced urinary calcium levels with an autosomal dominance inheritance pattern to the three out of four large types of this condition known. This rare condition goes largely undiagnosed as patients are largely asymptomatic and where symptoms are present, other causes of hypercalcemia are considered first. Hyperparathyroidism, super-imposing on FHH, is an even rarer occurrence. We present the case of an adult male with an initial provisional assessment of FHH, which was later confirmed with a genetic study. He went on to develop hyperparathyroidism (with evident enlarged parathyroid glands on Sestamibi parathyroid scan done, and an eventual histologic diagnosis of parathyroid adenoma after surgery). It remains to be established if this is an incidental occurrence or if there is a causal relationship between FHH and an onward development of parathyroid hypertrophy or adenoma(ta).

Dental considerations and management in Noonan Syndrome: A case report with review of literature

Noonan syndrome is a genetic disorder of autosomal dominance with an estimated prevalence of 1:1000 – 1:2500 live birth. The typical features include short stature, cardiovascular abnormalities and characteristics facial deformity. Dental features reported so far include malocclusion, dental caries, giant cell and cystic lesion. Multidisciplinary treatment plays a key role in the overall quality of life of the patient. This case report describes a 6-year-old boy with Noonan syndrome.

Identification of Missense ADGRV1 Mutation as a Candidate Genetic Cause of Familial Febrile Seizure 4

Febrile seizure (FS) is related to a febrile illness (temperature > 38 °C) not caused by an infection of central nervous system, without neurologic deficits in children aged 6–60 months. The family study implied a polygenic model in the families of proband(s) with single FS, however in families with repeated FS, inheritance was matched to autosomal dominance with reduced disease penetrance. A 20 month-old girl showed recurrent FS and afebrile seizures without developmental delay or intellectual disability. The seizures disappeared after 60 months without anti-seizure medication. The 35 year-old proband’s mother also experienced five episodes of simple FS and two episodes of unprovoked seizures before 5 years old. Targeted exome sequencing was conducted along with epilepsy/seizure-associated gene-filtering to identify the candidate causative mutation. As a result, a heterozygous c.2039A>G of the ADGRV1 gene leading to a codon change of aspartic acid to glycine at the position 680 (rs547076322) was identified. This protein’s glycine residue is highly conserved, and its allele frequency is 0.00002827 in the gnomAD population database. ADGRV1 mutation may have an influential role in the occurrence of genetic epilepsies, especially those with febrile and afebrile seizures. Further investigation of ADGRV1 mutations is needed to prove that it is a significant susceptible gene for febrile and/or afebrile seizures in early childhood.

Aarskog-Scott syndrome: clinical and molecular characterisation of a family with the coexistence of a novel FGD1 mutation and 16p13.11-p12.3 microduplication

Aarskog-Scott syndrome (AAS), also known as facio-genital dysplasia or faciodigitogenital syndrome, is a rare genetic disorder clinically characterised by facial, limb and genitalanomalies. Although also autosomal dominance and recessive patterns have been reported, up to now, only an X linked form associated to mutations of the FGD1 gene has been recognised as causative for this syndrome.In this case report, we describe a large Italian family in which three members across three generations show classical features of the syndrome. The youngest patient, the proband, and his mother were both molecularly studied and characterised for the not previously reported variant c.1828C>T (p. Arg610*) in the FGD1 gene but with the classic phenotype of AAS. Additionally, both the proband and his mother present a 2.5 Mb 16p13.11-p12.3 microduplication, a genetic variant still unclear for the phenotypic consequences: the co-occurrence of the two rare conditions is discussed for the possible clinical significance.

Class III malocclusion: an argument for early orthodontic treatment

Class III malocclusion is a complex multifactorial condition with many genetic and environmental influences. Most often the condition is inherited in a Mendelian autosomal dominant pattern. Early referral and treatment can lead to better outcomes in orthodontic therapy. The subject presented for an early orthodontic referral at age 5.5 and showed signs of future Class III malocclusion. A rapid maxillary expander was given as interventional treatment for one year. At age 11.5 the subject was treated with braces for 2 years. The outcome was a normal Class I occlusion. The subject’s mother had Class III malocclusion but was not evaluated early and was only able to establish an edge-to-edge Class III malocclusion as the best treatment outcome without orthognathic surgery. The subject’s grandmother was also Class III, establishing an autosomal dominance pattern of inheritance in the family. This case demonstrates the importance of the general dentist educating families about malocclusion and making orthodontic referrals as early as possible so the best treatment outcomes can be reached through orthodontic therapy.

Rendu-Osler-Weber Syndrome: A Case Report

Hereditary hemorrhagic telangectasia (HHT) or Rendu-Osler-Weber syndrome, is a rare genetic disorder with autosomal dominance and variable penetrance. The typical findings of the disease are telangiectasias in skin and mucous membranes, and arteriovenous malformations presenting in the organs like lung, intestine, brain and liver. It is characterized by the classic triad of recurrent epistaxis, mucocutaneous telangiectasias and visceral hemorrhages, with familial occurrence. This article describes a case of HHT of an adult patient, associated with multiple angiodysplasic injuries in the nasal mucosa, upper gastrointestinal tract, lungs and who presents continuous blood loss, resulting iron deficiency anemia. Based on clinical and diagnostic findings, we diagnosed this case as HHT, which has rarely been reported in our literature.

Familial os odontoideum

✓ A familial asymptomatic os odontoideum with a Klippel-Feil type II fusion of C-2 and C-3 is reported. The pattern of inheritance within this family is consistent with that of autosomal dominance. The index case, a 16-year-old boy, was studied with plain cervical spine x-ray films, lateral cervical tomography in flexion and extension, fluoroscopic evaluation of the subluxation, and magnetic resonance (MR) imaging of the spine in flexion and extension. In spite of the subluxation noted on flexion and extension, there was no evidence of cord compression on MR imaging. The etiology and management of this condition are discussed.