ABSTRACT
Chromosome 2q37 deletion syndrome is a rare chromosomal disorder characterized by mild to moderate developmental delay, brachydactyly of the third to fifth digits or toes, short stature, obesity, hypotonia, a characteristic facial appearance, and autism spectrum disorder. Here, we report on a patient with 2q37 deletion presenting with dilated cardiomyopathy (DCMP). Congenital heart malformations have been noted in up to 20% of patients with 2q37 deletions. However, DCMP has not been reported in 2q37 deletion patients previously. The patient exhibited the characteristic facial appearance (a flat nasal bridge, deep-set eyes, arched eyebrows, and a thin upper lip), developmental delay, mild mental retardation, peripheral nerve palsy, and Albright hereditary osteodystrophy (AHO)-like phenotypes (short stature and brachydactyly). Conventional chromosomal analysis results were normal; however, microarray-based comparative genomic hybridization revealed terminal deletion at 2q37.1q37.3. In addition, the patient was confirmed to have partial growth hormone (GH) deficiency and had shown a significant increase in growth rate after substitutive GH therapy. Chromosome 2q37 deletion syndrome should be considered in the differential diagnosis of patients presenting with AHO features, especially in the presence of facial dysmorphism. When patients are suspected of having a 2q37 deletion, high-resolution cytogenetic analysis is recommended.
Subject(s)
Humans , Autism Spectrum Disorder , Brachydactyly , Cardiomyopathy, Dilated , Chromosome Disorders , Comparative Genomic Hybridization , Cytogenetic Analysis , Cytogenetics , Deoxycytidine Monophosphate , Diagnosis, Differential , Eyebrows , Growth Hormone , Heart , Intellectual Disability , Muscle Hypotonia , Obesity , Paralysis , Peripheral Nerves , Phenotype , ToesABSTRACT
Pseudohypoparathyroidism (PHP) is a group of genetic disorders in which the kidneys fail to respond to parathyroid hormone. Genetic defects in the GNAS complex locus lead to reduced Gsalpha (alpha-subunit of the heterotrimeric stimulatory G protein) activity in PHP type Ia patients. These patients exhibit characteristics of Albright hereditary osteodystrophy (AHO) and hypocalcemia, increased parathyroid hormone, and resistance to other Gsalpha protein-coupled hormones. AHO has a wide range of manifestations such as short stature, obesity, round face, subcutaneous ossification, and bone shortening in the hands and feet. In this study, we present the case of a 47-yr-old woman who was diagnosed with PHP type Ia with AHO. She showed tetany, dizziness, irritability to light, decreased visual acuity, cognitive impairment, and motor dysfunction. Direct sequencing identified a heterozygous missense mutation in exon 6 (c.466G>A, p.Asp156Asn) in GNAS1. To our knowledge, this case is the first report in Korea of PHP type Ia caused by a heterozygous missense mutation in exon 6 (c.466G>A, p.Asp156Asn) in GNAS1.
Subject(s)
Female , Humans , Dizziness , Exons , Foot , Hand , Hypocalcemia , Kidney , Korea , Mutation, Missense , Obesity , Parathyroid Hormone , Pseudohypoparathyroidism , Tetany , Visual AcuityABSTRACT
Pseudohypoparathyroidism type Ia (PHP Ia) is a disorder characterized by multiform hormonal resistance including parathyroid hormone (PTH) resistance and Albright hereditary osteodystrophy (AHO). It is caused by heterozygous inactivating mutations within the Gs alpha-encoding GNAS exons. A 9-year-old boy presented with clinical and laboratory abnormalities including hypocalcemia, hyperphosphatemia, PTH resistance, multihormone resistance and AHO (round face, short stature, obesity, brachydactyly and osteoma cutis) which were typical of PHP Ia. He had a history of repeated convulsive episodes that started from the age of 2 months. A cranial computed tomography scan showed bilateral calcifications in the basal ganglia and his intelligence quotient testing indicated mild mental retardation. Family history revealed that the patient's maternal relatives, including his grandmother and 2 of his mother's siblings, had features suggestive of AHO. Sequencing of the GNAS gene of the patient identified a heterozygous nonsense mutation within exon 11 (c.637 C>T). The C>T transversion results in an amino acid substitution from Gln to stop codon at codon 213 (p.Gln213*). To our knowledge, this is a novel mutation in GNAS.
Subject(s)
Child , Humans , Male , Amino Acid Substitution , Basal Ganglia , Brachydactyly , Codon , Codon, Nonsense , Codon, Terminator , Exons , Hyperphosphatemia , Hypocalcemia , Intellectual Disability , Intelligence , Obesity , Osteoma , Parathyroid Hormone , Pseudohypoparathyroidism , SiblingsABSTRACT
We report a12-year-old child with pseudohypoparathyroidism (PHP) whose mother had pseudopseudohypoparathyroidism. The child had low serum calcium, high phosphorous and high parathormone (PTH) levels. PHP occurs due to a defect in the guanine nucleotide binding protein (G protein). She also had hypothyroidism which is known to utilize the G protein pathway. She developed T 1 diabetes mellitus (T1DM) while under follow-up. This is arguably the first time T1DM has been reported associated with PHP.
ABSTRACT
Pseudohypoparathyroidism due to deficient end organ response to parathyroid hormone (PTH) is characterized by hypocalcemia, hyperphosphatemia and increased serum PTH. We report a case of an 8-year-old girl with pseudohypoparathyroidism without features of Albright’s hereditary osteodystrophy. The case is of interest as the child on serial follow-up over a period of 2 years developed hypothyroidism. This is a rare feature seen in pseudohypoparathyroidism type1b.
ABSTRACT
The clinical and genetic data were retrospectively analyzed in a pedigree with pseudohypoparathyroidism type Ⅰ a.Clinically typical Albright hereditary osteodystrophy (AHO),hypocalcemia,hyperphosphatemia,and PTH- and TSH-resistance were manifested in the proband,but not in his brother and parents.The proband's symptom of epilepsy was alleviated by treatment with calcium and vitamin D,which was of no avail in regard to AHO.After GNAS1 genes were sequenced and compared with the GenBank data among the family members,a deletion of c.1107_1108 ( p.Glu370ArgfsX11 ) in exon l3 of GNAS1 gene leading to a frameshift mutation was found in the proband and his mother.It suggested that the GNAS1 gene mutation might be related to the pathogenesis of the disease.
ABSTRACT
A 36 year-old man and his 6 month-old daughter presented with multiple, slightly depressed, skin-colored, hard nodules and plaques on the abdomen, back, and both extremities. They also showed abnormal physical appearance, including short stature and neck, round face, and short digits, which suggested Albright's hereditary osteodystrophy (AHO). Histopathologically, various sized bony spicules were present in the dermis. The laboratory results showed normal serum calcium, phosphorus and parathyroid hormone levels. On the basis of clinical, laboratory and histologic findings, we diagnosed these cases as Albright's hereditary osteodystrophy with cutaneous ossification occurring in pseudopseudohypoparathyroidism.
Subject(s)
Abdomen , Calcium , Dermis , Extremities , Fibrous Dysplasia, Polyostotic , Neck , Nuclear Family , Parathyroid Hormone , Phosphorus , PseudopseudohypoparathyroidismABSTRACT
A 36 year-old man and his 6 month-old daughter presented with multiple, slightly depressed, skin-colored, hard nodules and plaques on the abdomen, back, and both extremities. They also showed abnormal physical appearance, including short stature and neck, round face, and short digits, which suggested Albright's hereditary osteodystrophy (AHO). Histopathologically, various sized bony spicules were present in the dermis. The laboratory results showed normal serum calcium, phosphorus and parathyroid hormone levels. On the basis of clinical, laboratory and histologic findings, we diagnosed these cases as Albright's hereditary osteodystrophy with cutaneous ossification occurring in pseudopseudohypoparathyroidism.
Subject(s)
Abdomen , Calcium , Dermis , Extremities , Fibrous Dysplasia, Polyostotic , Neck , Nuclear Family , Parathyroid Hormone , Phosphorus , PseudopseudohypoparathyroidismABSTRACT
Primary osteoma cutis is characterized by the formation of normal bone tissue in the dermis or subcutis without any underlying tissue abnormality or pre-existing calcification. This illness is associated with Albright hereditary osteodystrophy (AHO), which is characterized by such physical features as a short stature, round face, obesity, brachydactyly and osteoma cutis. Pseudohypoparathyroidism (PHP) is an inherited metabolic disorder that's characterized by resistance to parathyroid hormone, and PHP is present in most AHO patients. An AHO phenotype without hormonal resistance is called pseudopseudohypoparathyroidism (PPHP). Osteoma cutis is less common in patients with PPHP than in patients with PHP. We present here a case of osteoma cutis as the cardinal manifestation of AHO associated with PPHP. Osteoma cutis is an important sign of AHO and its significance should not be overlooked, even if the patient has normal values on the serum biochemical tests.
Subject(s)
Humans , Alkenes , Bone and Bones , Bone Diseases, Metabolic , Brachydactyly , Dermis , Fibrous Dysplasia, Polyostotic , Obesity , Ossification, Heterotopic , Osteoma , Parathyroid Hormone , Phenotype , Pseudohypoparathyroidism , Pseudopseudohypoparathyroidism , Reference Values , Skin Diseases, GeneticABSTRACT
Primary osteoma cutis is characterized by the formation of normal bone tissue in the dermis or subcutis without any underlying tissue abnormality or pre-existing calcification. This illness is associated with Albright hereditary osteodystrophy (AHO), which is characterized by such physical features as a short stature, round face, obesity, brachydactyly and osteoma cutis. Pseudohypoparathyroidism (PHP) is an inherited metabolic disorder that's characterized by resistance to parathyroid hormone, and PHP is present in most AHO patients. An AHO phenotype without hormonal resistance is called pseudopseudohypoparathyroidism (PPHP). Osteoma cutis is less common in patients with PPHP than in patients with PHP. We present here a case of osteoma cutis as the cardinal manifestation of AHO associated with PPHP. Osteoma cutis is an important sign of AHO and its significance should not be overlooked, even if the patient has normal values on the serum biochemical tests.
Subject(s)
Humans , Alkenes , Bone and Bones , Bone Diseases, Metabolic , Brachydactyly , Dermis , Fibrous Dysplasia, Polyostotic , Obesity , Ossification, Heterotopic , Osteoma , Parathyroid Hormone , Phenotype , Pseudohypoparathyroidism , Pseudopseudohypoparathyroidism , Reference Values , Skin Diseases, GeneticABSTRACT
Albright's hereditary osteodystrophy (AHO) has a broad spectrum of physical findings, including short stature, flattened nasal bridge, round facies, obesity, skeletal anomalies of the hands with brachydactyly, osteoma cutis, mental retardation, dental defects, cataracts, and calcification in the basal ganglia. It also includes endocrinologic abnormalities such as pseudohypoparathyroidism and pseudopseudohypoparathyroidism. Primary osteoma cutis, which can precede other physical findings of AHO, might be a diagnostic clue for AHO. Therefore, close follow-up and regular laboratory tests should be done to detect the early development of AHO in young children with primary osteoma cutis. Early diagnosis and treatment of AHO can prevent irreversible mental retardation and developmental delay.
Subject(s)
Child , Humans , Basal Ganglia , Bone Diseases, Metabolic , Brachydactyly , Cataract , Early Diagnosis , Facies , Fibrous Dysplasia, Polyostotic , Hand , Intellectual Disability , Obesity , Ossification, Heterotopic , Osteoma , Pseudohypoparathyroidism , Pseudopseudohypoparathyroidism , Skin Diseases, GeneticABSTRACT
Albright's hereditary osteodystrophy is an inherited syndrome that encompasses endocrinologic anomaly of pseudohypoparathyroidim or less commonly, pseudo-pseudohypoparathyroidism and various physical stigmata such as mental retardation, short stature, skeletal anomaly of the hands, abnormal dentition, round facies, and osteoma cutis. Primary osteoma cutis in this syndrome presents at birth or in early infancy, preceding most of the other manifestations. This case is a typical presentation with osteoma cutis as the sole initial manifestation. Rather unfamiliar to dermatologists, Albright's hereditary osteodystrophy still deserves to be included in the differentials when an isolated case of osteoma cutis presents in a young child.
Subject(s)
Child , Humans , Christianity , Dentition , Facies , Hand , Intellectual Disability , Osteoma , Parturition , PseudopseudohypoparathyroidismABSTRACT
In pseudohypoparathyroidism as reported by Albright in 1942, the parathyroid gland can normally synthesize and secrete parathyroid hormone(PTH). Pseudohypoparathyroidism has a similar biochemical finding with hypoparathyroidisms like hypocalcemia and hyperphosphatemia due to target tissue resistance to PTH. Administered PTH does not raise the serum levels of calcium and urinary phosphate. PTH activates G-protein in peripheral tissue and adenylate cyclase through a second messenger, cAMP. Pseudohypoparathyroidism produces hyperphosphatemia and hypocalcemia because of the resistance to PTH in peripheral tissue due to a defect of G-protein, although it releases PTH normally. According to the mechanism of resistance, pseudohypoparathyroidism is classified into types: Ia, Ib, Ic and psedopseudohypoparathyroism. Type Ia is accompanied by congenital growth retardation and abnormal bony development that shows mental retardation, obesity, low height, round face, short metacarpal bone and metatarsal bone, ectopic calcification, etc. We report a case of pseudohypoparathyroidism in a premature who shows hypocalcemia, hyperphosphatemia, elevation of serum PTH and 24 hr urinary basal c-AMP in biochemical tests without Albright's hereditary osteodystrophy at physical examination, accompanied by a spontaneous fracture in the femur.
Subject(s)
Humans , Infant, Newborn , Adenylyl Cyclases , Calcium , Femur , Fractures, Spontaneous , GTP-Binding Proteins , Hyperphosphatemia , Hypocalcemia , Infant, Premature , Intellectual Disability , Metatarsal Bones , Obesity , Parathyroid Glands , Physical Examination , Pseudohypoparathyroidism , Second Messenger SystemsABSTRACT
We describe a rare case of pseudopseudohypoparathyroidism (PPHP) with benign intracranial hypertension (BIH). A 16 year-old male presented with headache, vomiting, ocular pain, blurred vision, and diplopia following minor head trauma. He showed developmental delay, short stature and short metacarpals and phalanges, which suggested Albright's hereditary osteodystrophy. Neurologic examination revealed bilateral sixth cranial nerve palsy and bilateral papilledema. Lumbar puncure disclosed an elevated opening CSF pressure with normal biochemical and celluar find-ings. However, the levels of serum calcium, phosphorus and parathyroid hormone were within the normal limits and chromosomal analyses were normal. Brain MRI revealed normal ventricular size and no structural abnormality. We concluded that PPHP seemed to have a key role for the genesis of BIH in this case, although previous mild head trauma might have a precipitating effect.
Subject(s)
Adolescent , Humans , Male , Abducens Nerve Diseases , Brain , Calcium , Craniocerebral Trauma , Diplopia , Headache , Magnetic Resonance Imaging , Metacarpal Bones , Neurologic Examination , Papilledema , Parathyroid Hormone , Phosphorus , Pseudopseudohypoparathyroidism , Pseudotumor Cerebri , VomitingABSTRACT
Pseudohypoparathyroidism(PHP) is a genetic disorder characterized by target cell resistance to the effect of parathyroid hormone(PTH). The disorder is classified into type I a, I b, I c and II depending on the phenotype and biochemical findings. In type I a, urinary cyclic AMP and urinary phosphate excretion are not increased after PTH stimulation because of deficient G unit activity in target cells. Deficiency of the G unit is a generalized cellular defect and accounts for the association of other endocrine disorders with type I a PHP. Type I b PHP shows resistance to PTH but not to other hormones and normal phenotypic appearance. In type I c PHP affected children have defect in catalytic unit of adenylate cyclase and in addition to resistance to PTH, resistance to the metabolic effects of TSH, gonadotropins, and glucagon may be detected. Typical appearance of Albright's hereditary osteodystrophy is common in PHP type Ia and Ic. In type II PHP, urinary cyclic AMP response is generated but this does not lead to phosphaturia. We experienced two patients with PHP. One is a 11-year-old girl diagnosed type I a PHP and the other is a 11-year-old boy suspected type I b PHP. They visited emergency room because of tetanic movement. Both patients had no previous history of tetany and showed low serum calcium level, high phosphorus level and high PTH level. The girl had typical features of Albright's hereditary osteodystrophy such as round face, short neck, obese feature, brachydactyly and mental retardation but didn't have basal ganglia calcification on brain CT. The boy showed normal appearance and no mental retardation.