Distal arthrogryposis 5: a dominant syndrome of peripheral contractures and ophthalmoplegia

A four-generation family with distal arthrogryposis 5 is described. All affected members had limitations of ocular motility and some had ptosis. Restrictive lung disease is a feature in most affected patients in this family. It is possible that this syndrome may be due to a muscle abnormality.     

Arthrogryposis, perthes disease, and upward gaze palsy: a novel autosomal recessive syndromic form of arthrogryposis

In this article, the unusual combination of arthrogryposis, upward gaze palsy, and Perthes disease in two sisters and their cousin who are all part of an extended consanguineous Saudi family is reported. All patients had difficult to control bronchial asthma and subtle facial dysmorphism. Two of the three had pyloric stenosis, two were intellectually normal, and one had academic problems but had a history of birth hypoxia. Pedigree is consistent with an autosomal recessive mode of inheritance. Lack of previous reports suggests this represents a novel syndromic form of arthrogryposis.     

Spondylo-metaphyseal dysplasia Algerian type: confirmation of a new syndrome

We report on a further case of a recently described type of spondylo-metaphyseal dysplasia in a 12(10/12)-year-old Polish boy. The original paper described the disorder in five relatives in an Algerian family.     

Familial distal arthrogryposis with craniofacial abnormalities: a new subtype of type II?

We report on 5 relatives in 3 generations with an apparent new type of distal arthrogryposis. These individuals have manifestations of type I distal arthrogryposis, but in addition, have craniofacial anomalies that include facial asymmetry, hypertelorism, downslanting palpebral fissures, high nasal bridge, malar hypoplasia, micrognathia, highly arched palate, notched chin, and posteriorly angulated ears. Their intelligence is normal. Although these manifestations preclude us from placing this family in the type I (isolated) distal arthrogryposis category, we also are unable to place them in any of the recognized subtypes of type II distal arthrogryposis. Thus, we think this family may have a previously undescribed form of autosomal dominant type II distal arthrogryposis.     

Distal arthrogryposis type 1: Clinical analysis of a large kindred

We describe the clinical findings of 15 individuals in a large kindred affected with distal arthrogryposis type 1A (DA1A). The most consistent findings among individuals were overlapping fingers at birth, abnormal digital flexion creases, and foot deformities, including talipes equinovarus and vertical talus. There was marked intrafamilial variation in the expression of DA1A. Linkage mapping of the locus for DA1A suggests that the use of strict diagnostic criteria excludes unaffected individuals rigorously, but can produce incomplete ascertainment of affected individuals. In the context of an affected family, the range of phenotypes consistent with a diagnosis of DA1A needs to be expanded. © 1996 Wiley-Liss, Inc.     

A new form of autosomal dominant arthrogryposis.

We report a man and his son with congenital limb contractures, limitation of ocular movements, and an electroretinal abnormality. They appear to have an autosomal dominant form of arthrogryposis, distinguishable from other previously classified forms of this disorder.     

Distal arthrogryposis type II: a family with varying congenital abnormalities

Five family members with distal arthrogryposis in two generations are reported. Cleft lip and palate, micrognathia, ptosis, webbed neck, kyphoscoliosis, and short stature are seen in one or more affected family members. All individuals with distal arthrogryposis also have trismus. This family does not fit any of the recently proposed five subcategories of type II distal arthrogryposis, nor does it fit any other recognized autosomal dominant condition with distal contractures.     

Mental retardation, Robin sequence, and brachydactyly: further confirmation of a new syndrome

Recently we reported two sibs, brother and sister, with a new multiple congenital anomalies/mental retardation (MCA/MR) syndrome characterized by mild to moderate psychomotor delay, Robin sequence, distinctive facial appearance, and brachydactyly. We have subsequently observed a similar pattern of anomalies in two unrelated patients who also showed additional clinical findings. This new observation supports the existence of a new syndrome and expands the phenotypic spectrum of the condition.     

Mutations in ERGIC1 cause Arthrogryposis multiplex congenita,neuropathic type

Arthrogryposis multiplex congenita (AMC) is heterogeneous group of disorders characterized by non‐progressive joint contractures from birth that involve more than 1 part of the body. There are various etiologies for AMC including genetic and environmental depends on the specific type, however, for most types, the cause is not fully understood. We previously reported large Israeli Arab kindred consisting of 16 patients affected with AMC neuropathic type, and mapped the locus to a 5.5 cM interval on chromosome 5qter. Using whole exome sequencing, we have now identified homozygous pathogenic variant in the ERGIC1 gene within the previously defined linked region. ERGIC1 encodes a cycling membrane protein which has a possible role in transport between endoplasmic reticulum and Golgi. We further show that this mutation was absent in more than 200 samples of healthy unrelated individuals of the Israeli Arab population. Thus, our findings expand the spectrum of hereditary AMC and suggest that abnormalities in protein trafficking may underlie AMC‐related disorders.     

Pulmonary disease is a component of distal arthrogryposis type 5

We report on a three-generation family with distal arthrogryposis type 5 (DA5). The family has four affected members in three generations with an apparent autosomal dominant pattern of inheritance. Three affected individuals were examined. All have distal joint contractures with absent flexion creases, limited mobility of all small and large joints, unusual stance with shortened heel cords and pes cavus, firm muscles, short stature, decreased extraocular movements, and pectus excavatum. The propositus has pulmonary hypertension secondary to chronic hypoxia from restrictive chest disease, alveolar hypoventilation, and residence at 7,000 feet above sea level. Cardiac catheterization documented pulmonary artery pressure of 54 mmHg and a pulmonary capillary wedge pressure of 10 mmHg. Pulmonary function tests showed severe chest restriction (forced vital capacity 30% of predicted; total lung capacity 51% predicted); and reduction of maximal inspiratory and expiratory pressures. Arterial blood gases documented alveolar hypoventilation. Restrictive chest disease is a component of DA5. This implies involvement of the skeletal, and/or respiratory muscles. All individuals diagnosed with DA5 should be evaluated for chest disease, alveolar hypoventilation, as treatment of chronic hypoxia may delay or reverse pulmonary hypertension.     

Restrictive dermopathy, a lethal form of arthrogryposis multiplex with skin and bone dysplasias: three new cases and review of the literature.

Restrictive dermopathy is a rare, lethal autosomal recessive syndrome. We report on 3 unrelated affected stillborn infants of consanguineous parents. Clinical findings include a tight, thin, translucent, taut skin, which tears spontaneously in flexion creases, arthrogryposis multiplex congenita (including the temporomandibular joint), enlarged fontanelles, typical face and dysplasia of clavicles and long bones. Histologic abnormalities include hyperplastic, abnormally keratinized epidermis, reduced tonofilaments, thin, compact dermis with hypoplasia of the elastic fibres, and abnormal subcutaneous fat. Fifteen previous cases are reviewed.     

罕见膝反屈型先天性多发性关节挛缩症的手术治疗

目的：探讨罕见膝反屈型先天性多发性关节挛缩症(Arthrogryposis面上multiplex congenita，AMC)的手术治疗方法及疗效。方法：3例膝反屈型AMC中，2例接受了手术治疗，每例均分两期施行16个手术。第1期下肢手术包括腱切断、腱延长、关节凹侧关节囊切开和切除术，股骨下端旋转性截骨及畸形足的三关节融合术；第2期上肢手术为肱骨下端切骨术及手部肌力平衡术。结果：2例均获十分满意的结果，无畸形复发。结论：选择恰当的术式治疗膝反屈型AMC是很有效的。     

Severe type II Gaucher disease with ichthyosis, arthrogryposis and neuronal apoptosis: molecular and pathological analyses

Severe infantile Gaucher disease associated with ichthyosis and neonatal death is a rare subgroup of Type II Gaucher disease. This group of infants has little, if any, detectable beta-glucocerebrosidase activity, and prior genetic analyses have been limited in detecting the mutations responsible for this phenotype. We document an Hispanic infant succumbing with arthrogryposis and collodion membrane covering the skin who had no detectable beta-glucocerebrosidase activity in tissue samples and who was homozygous for a rare recombinant allele, RecNciI. Microscopic evaluation demonstrated accumulation of Gaucher cells in visceral organs and extensive loss of neurons in the anterior horns, brainstem, and cortex of the nervous system. The apoptosis of neuronal cells from the anterior horns and brainstem are a reasonable explanation for the arthrogryposis and neonatal death, respectively.     

Oto-onycho-peroneal syndrome: confirmation of a syndrome.

We report two sibs with a similar syndrome of abnormal external ears, peculiar facial features, nail hypoplasia, a bilateral fibrous fusion of the outer third of the clavicle and the scapular spine, and the absence of a normal acromioclavicular joint. The present patients represent the fourth and fifth cases of the oto-onycho-peroneal syndrome (MIM 259780).     

PIEZO2 deficiency is a recognizable arthrogryposis syndrome: A new case and literature review

PIEZO2 encodes a mechanically activated cation channel, which is abundantly expressed in dorsal root ganglion neuron and sensory endings of proprioceptors required for light touch sensation and proprioception in mice. Biallelic loss‐of‐function mutations in PIEZO2 (i.e., PIEZO2 deficiency) were recently found to cause an arthrogryposis syndrome. Sixteen patients from eight families have been reported to date. Herein we report a new case, including detailed clinical characteristics and courses as well as comprehensive neurological features. The patient was a 12‐year‐old girl presenting with congenital multiple contractures, progressive severe scoliosis, prenatal‐onset growth impairment, motor developmental delay with hypotonia and myopathy‐like muscle pathology, mild facial features, and normal intelligence. Her neurological features included areflexia, impaired proprioception, and decreased senses. Neurophysiological examination revealed decreased amplitude of sensory nerve action potentials, absent H reflex, and prolongation of central conduction times. Clinical exome sequencing revealed a novel homozygous frameshift mutation in PIEZO2 (NM_022068: c.4171_4174delGTCA: p.Val1391Lysfs*39) with no detectable mRNA expression of the gene. PIEZO2 deficiency represents a clinical entity involving characteristic neuromuscular abnormalities and physical features. Next generation sequencing‐based comprehensive molecular screening and extensive neurophysiological examination could be valuable for diagnosis of the disorder.