Brachydactyly C,short stature,and hip dysplasia

Short stature may be a component of the brachydactyly C syndrome. A family is presented in which the propositus has brachydactyly C, short stature, and hip dysplasia.     

Brachydactyly type A-4 (Temtamy type) with short stature in a Japanese girl and her mother

We report on a Japanese girl and her mother with brachydactyly. Their 2nd and 5th middle phalanges were short and the latter was fused with the distal phalanx in one of the patients. Length and shape of proximal and distal phalanges as well as metacarpals seemed normal. These findings are consistent with brachydactyly type 4-A, which is a rare subtype and has not been adequately documented. Short stature was reported only in some cases of brachydactyly type A-1, A-6, C, and E, but not in the other subtypes. Our patients with type A-4 brachydactyly also had short stature. © 1993 Wiley-Liss, Inc.     

Classification and identification of inherited brachydactylies

A search for patterns of malformation in the brachydactylies has resulted in new ways to identify the different types. Type A-1 can be characterised by a proportionate reduction of the middle phalanges. Type B is thought to be an amputation-like defect. In type C the fourth middle phalanx is usually the longest, and type E (Riccardi and Holmes, 1974) is characterised by short metacarpals and short distal phalanges. Short stature is usually present in type A-1 and type E brachydactyly (Riccardi and Holmes, 1974) and it may be present in some individuals with brachydactyly C. As short children have short hands, it is possible that in patients with very mild expressions of brachydactyly the cause of the short stature may be overlooked. It is suggested that in every child with proportionate short stature the hands should be carefully examined. If the hands are disproportionately short, if any distal creases are missing, if there is a shortening, however mild, of any finger, if any metacarpals are short, then it is important to have -rays to look for brachydactyly A-1, C, or E.

Much information is still needed. It is important in future reports to have skeletal surveys, pattern profile analyses, and to note the height of children with brachydactyly C. Most interesting of all will be when fetal limbs of each type become available for study.

     

Brachydactyly, distal symphalangism, scoliosis, tall stature, and club feet: a new syndrome.

Five members of a kindred with brachydactyly and distal symphalangism, normal stature, pes cavus, and scoliosis were ascertained. The pedigree was consistent with autosomal dominant inheritance. The combination of clinical and radiological features is believed to be distinct from those previously reported in patients with brachydactyly/symphalangism.     

Short trunk stature,brachydactyly, and platyspondyly in three sibs: a new form of brachyolmia or a new skeletal dysplasia?

We present a 27-year-old girl with short trunk stature, generalized rectangular platyspondyly and strike precocious calcification of costal cartilage. She had also brachydactyly, small nails, strabismus and delay of menarche. Her 16-year-old sister had also short trunk stature with severe kyphoscoliosis, hearing loss, brachydactyly, platyspondyly and mild precocious calcification of costal cartilages. Their 12-year-old brother had short trunk stature, kyphoscoliosis, brachydactyly, and platyspondyly but did not show precocious calcification of costal cartilage. The patients shared the following features: short trunk stature, brachydactyly, severe rectangular platyspondyly, broad and short femoral necks and hypoplasia of the ileum. In addition, the older sister had strike precocious calcification of costal cartilage while her sister and brother had severe kyphoscoliosis. Although short trunk stature and severe rectangular platyspondyly without significant epiphyseal or metaphyseal changes were in favor of Hobaek type brachyolmia, this diagnosis was not considered, both because, there were no specific radiological findings of this syndrome, such as elongated vertebral bodies extending beyond the pedicles laterally and all of the patients had brachydactyly which was not present in Hobaek type brachyolmia. The parents were healthy and first cousins signifying autosomal recessive inheritance. We considered that the patients could be affected by a new distinct autosomal recessive type brachyolmia or a new skeletal dysplasia.     

Short stature,brachydactyly, nail dysplasia,and mental retardation: Further observation of the Tonoki syndrome

We studied a patient with microcephaly, short stature, type B brachydactyly, nail dysplasia, skeletal anomalies, and mental retardation. The mother of the propositus has brachydactyly of thumbs and a similar physiognomy without mental retardation. This appears to be another observation of the Tonoki syndrome, a distinct autosomal dominant or X-linked clinical entity. Am. J. Med. Genet. 80:403–405, 1998. © 1998 Wiley-Liss, Inc.     

Short stature, brachydactyly, and Peters'' anomaly (Peters''-plus syndrome): confirmation of autosomal recessive inheritance.

Two sibs with a phenotype characterised by short stature, brachydactyly, and ocular anomalies (Peters' anomaly) are reported (Peters'-plus syndrome). The consanguinity is in agreement with the proposed autosomal recessive inheritance.     

Facial phenotype allows diagnosis of Mowat-Wilson syndrome in the absence of Hirschsprung disease

In a Dutch kindred we have identified a deletion of the DJ-1 gene, leading to autosomal-recessive parkinsonism. The parkinsonism patients also had short stature and brachydactyly. In the family and a control group from the same community, we used the DJ-1 deletion as a marker for the originally linked PARK7 region and found a significant association with body height (P = 0.005), which suggests a gene in linkage disequilibrium with DJ-1 to be implicated in short stature. Analysis of hand-bone length showed incomplete segregation of the PARK7 region with brachydactyly, such that a gene in PARK7 is unlikely to fully explain the brachydactyly. Since the bone length reduction was more pronounced in the homozygous parkinsonism patients than in their heterozygous relatives, however, the PARK7 region may contain a modifier gene for growth.     

Floating-Harbor syndrome in two unrelated girls: mild short stature in one patient and effective growth hormone therapy in the other.

We report two female patients, 11 and eight years old, with clinical findings consistent with the Floating-Harbor syndrome (FHS). The first patient presented with characteristic facial features, brachydactyly, broad thumbs, and delay of speech development, but less pronounced short stature (-2 standard deviation (SD) below mean) than previously reported. The second patient presented with short stature, characteristic facial features, brachydactyly, and delay of speech as well as mental development; she was successfully treated with growth hormone. Metacarpophalangeal pattern profiles (MCPP) were performed in both patients and compared to those of previously published patients.     

Floating‐Harbor syndrome in two unrelated girls: Mild short stature in one patient and effective growth hormone therapy in the other

We report two female patients, 11 and eight years old, with clinical findings consistent with the Floating‐Harbor syndrome (FHS). The first patient presented with characteristic facial features, brachydactyly, broad thumbs, and delay of speech development, but less pronounced short stature (?2 standard deviation (SD) below mean) than previously reported. The second patient presented with short stature, characteristic facial features, brachydactyly, and delay of speech as well as mental development; she was successfully treated with growth hormone. Metacarpophalangeal pattern profiles (MCPP) were performed in both patients and compared to those of previously published patients. © 2001 Wiley‐Liss, Inc.     

Natural history of clinical features in two brothers with acromesomelic dysplasia related to PRKG2

Acromesomelic dysplasias (AMD) are a group of skeletal dysplasia characterized by shortening of the middle and distal segments of the limbs. Recently, biallelic PRKG2 variants have been reported to cause a new type of AMD. We detected biallelic novel variant (c.1635-1G > C) in PRKG2 in two brothers with mild to severe short stature, short limbs, cubitus varus, and brachydactyly. Radiological examination showed platyspondyly with anterior beaking of the vertebral bodies, stubby long bones with metaphyseal flaring and moderate brachydactyly with cone-shaped epiphyses of the middle and proximal phalanges. Upper limb proportions of the older brother were clinically classified as rhizomelic, however radiologic findings supported acromesomelia, along with the elbow limitation. Annual follow-ups of the older brother from the age of 5 to 20 years revealed progression of short stature with age but platyspondyly and anterior beaking became less conspicuous. The younger brother showed milder short stature and less conspicuous disproportion of the limbs than those of the older brother; however, platyspondyly and anterior beaking were more prominent on the radiographs obtained at the same age. In conclusion, this report provides new insights into the natural history of AMD type PRKG2 confirming the intrafamilial heterogeneity.     

Severe mental retardation, short stature, facial anomalies, joint laxity, and dislocations in two sisters: previously undescribed MCA/MR syndrome

We describe two sisters with short stature, obesity, "bulbous" nasal tip, microretrognathism, brachydactyly, joint hyperlaxity and dislocation, and mental retardation. Skeletal surveys disclosed widened mandibular angles, thin temporal processes, hypoplastic clavicles, short distal ends of ulnae, short fourth metacarpals, and dislocation of hips, elbows, and thumbs. The parents are first cousins. To the best of our knowledge, this combination of multiple congenital anomalies and mental retardation has not been reported before.     

Brachydactyly type A1 with short humerus and associated skeletal features

We report on a three-generation family affected with an osteochondrodysplasia transmitted as an autosomal dominant trait. The phenotype consists of short humerus, curved radius with accessory ossification centre at the proximal third of ulna, variable short stature and brachydactyly, and has not been reported to the best of our knowledge. The brachydactyly falls into the brachydactyly A1 category (especially short 2nd, 4th, and 5th middle phalanges). A unique feature in one family member is triphalangeal thumbs. Vertebrae are normal. Mental development is normal and deafness is seen in some of the family members. A mutation was excluded by sequencing the entire coding regions of the IHH gene encoding the Indian Hedgehog protein and the GDF5 gene. This condition is a novel chondrodyplasia phenotype or possibly one end of the spectrum of the brachydactyly A1.     

Short stature, brachydactyly, small ears, and a pattern of minor anomalies in brother and sister born to consanguineous parents: a hitherto unreported syndrome?

A 13-year-old boy and his 28-year-old sister had short stature, obesity, and a pattern of minor anomalies including a sloping, narrow forehead; small ears; a narrow nose with prominent bridge and long septum; short upper lip; receding mandible; and short limbs with brachydactyly and clinodactyly of little fingers. The boy also had hypoplastic external genitalia and elevated FSH. Both are of normal intelligence. There is remote consanguinity of the (normal) parents. The 2 sibs probably represent a hitherto un-recognized syndrome of possibly autosomal recessive inheritance.     

Further delineation of the phenotype caused by loss of function mutations in PRMT7

PRMT7 encodes for an arginine methyltransferase that methylates arginine residues on various protein substrates and has been shown to play a role in various developmental processes. Mutations in PRMT7 have been recently shown to be implicated in a phenotype with intellectual disability, short stature and brachydactyly, and considered to be a phenocopy of pseudohypoparathyroidism. We report a patient with short stature, psychomotor delay, hearing loss and brachydactyly, for whom whole exome sequencing detected two mutations in PRMT7 and parental segregation studies detected biallelic mutation inheritance. Few patients with biallelic PRMT7 mutations have been reported so far in the literature. We report a new patient and review all reported cases to date to delineate the clinical manifestations that may help in diagnosis this disorder, known as Short Stature, Brachydactyly, Intellectual Developmental Disability, and Seizures syndrome, allowing appropriate management and genetic counselling.     

Omani-type spondyloepiphyseal dysplasia with cardiac involvement caused by a missense mutation in CHST3

We describe a family with progressive skeletal dysplasia and severe spinal involvement, short stature, premature arthrosis and joint contractures diagnosed as spondyloepiphyseal dysplasia Omani type. Mutation analysis in CHST3 , the gene encoding for the chondroitin 6- O -sulfotransferase-1 (C6ST-1), revealed a homozygous missense mutation (T141M) in exon 3 in all three affected members of the family. Using recombinant C6ST-1, we showed that the identified missense mutation results in a reduction of C6ST-1 activity to 24–29% of the wild type protein. In addition to the previously noted skeletal features, affected members of this family also had cardiac involvement including mitral, tricuspid and/or aortic regurgitations and type E brachydactyly.     

Differential diagnosis in young women with oligomenorrhea and the pseudo-pseudohypoparathyroidism variant of Albright's hereditary osteodystrophy

Oligomenorrhea was the reason for consultation in three individuals (two sisters and one unrelated woman) with the pseudo-pseudohypoparathyroidism (PPHP) variant of Albright's hereditary osteodystrophy (AHO). All had short stature, Ullrich-Turner-like signs, acral anomalies typical of AHO/brachydactyly E, and hypogonadism. One of the three individuals also had reduced erythrocyte NS (a membrane nucleotide regulatory protein that is required for functional coupling of stimulatory hormone receptors and catalytic adenylate cyclase) activity as described in the pseudohypoparathyroidism variant of AHO. The differential diagnosis of young women with the PPHP phenotype is discussed with special reference to Ullrich-Turner syndrome, brachydactyly E, the "resistant ovary" syndrome, and acrodysostosis.     

Microcephalic osteodysplastic dysplasia

We Present two patients with a distinct facial phenotype, short stature, brachydactyly, clubfoot deformities, cataracts, microcephaly, and normal intelligence. Similar radiographic abnormalities of the spine, long bones, hands, and feet were noted. These patients are similar to 2 males previously described by Saul and Wilson [1990: Am J Med Genet 35:388–393]. These 4 patients appear to have a unique skeletal dysplasia characterized by microcephaly, distinct facial phenotype, multisystem abnormalities, and short stature of postnatal onset. © 1994 Wiley-Liss, Inc.     

A distinctive autosomal recessive syndrome of severe disproportionate short stature with short long bones, brachydactyly, and hypotrichosis in two consanguineous Arab families

Disproportionate short stature is a heterogeneous group of hereditary disorders, which are classified according to their mode of inheritance, their clinical skeletal and non-skeletal manifestations, and their radiological characteristics. Herein, we inform on eight individuals with severe disproportionate short stature from two unrelated consanguineous families of Arab-Muslim ancestry. The adult height of the affected individuals is between 112 cm and 127 cm, and is due to pre- and post-natal growth retardation, which probably manifests as early as the second trimester of pregnancy. At a young age, the phenotype is characterized by a short stature, a relatively large head, and a long triangular face, and this phenotype later evolves to one with in which the head is relatively small, the mandible is large and pointy. The affected individuals have normal cognitive abilities and lack any neurological deficits. Other typical features include a prominent nose, a voice with an unusual high-pitched sound, relatively small ears, clinodactyly, brachydactyly, small hands, hypoplastic fingernails, a waddling gait, and sparse hair post-pubertally. Typical skeletal changes include short long bones, especially the femurs and humeri, with mild metaphyseal changes and very short femoral necks. After due consideration of the other hereditary causes of disproportionate short stature and close examination of the pedigrees of the two families, we concluded that these eight individuals have the same hitherto unreported form of severe disproportionate short stature that is inherited in the autosomal recessive mode.     

Differential diagnosis in young women with oligomenorrhea and the pseudopseudohypoparathyroidism variant of Albright's hereditary osteodystrophy

Oligomenorrhea was the reason for consultation in three individuals (two sisters and one unrelated woman) with the pseudo-pseudohypoparathyroidism (PPHP) variant of Albright's hereditary osteodystrophy (AHO). All had short stature, Ullrich-Turner-like signs, acral anomalies typical of AHO/brachydactyly E, and hypogonadism. One of the three individuals also had reduced erythrocyte N^s (a membrane nucleotide regulatory protein that is required for functional coupling of stimulatory hormone receptors and catalytic adenylate cyclase) activity as described in the pseudohypoparathyroidism variant of AHO. The differential diagnosis of young women with the PPHP phenotype is discussed with special reference to Ullrich-Turner syndrome, brachydactyly E, the “resistant ovary” syndrome, and acrodysostosis.