Bilateral macrodystrophia lipomatosa with syndactyly: a case report and literature review.

Macrodystrophia lipomatosa is a rare, non-hereditary form of congenital local gigantism characterised by enlargement and hypertrophy of all mesenchymal tissue components with a disproportionate increase in adipose tissue. This form of macrodactyly has been reported in association with other anomalies including polydactyly, brachydactyly, syndactyly, and symphalangism. We describe a previously unreported case of bilateral upper extremity macrodystrophia lipomatosa with syndactyly in a 23-month-old boy. In this report, we emphasise the importance of establishing a diagnosis with imaging and review the described surgical approaches to treating this difficult condition.

Hereditary pituitary hyperplasia with infantile gigantism.

CONTEXT: We report hereditary pituitary hyperplasia. OBJECTIVE: The objective of the study was to describe the results of the clinical and laboratory analysis of this rare instance of hereditary pituitary hyperplasia. DESIGN: The study is a retrospective analysis of three cases from one family. SETTING: The study was conducted at the National Institutes of Health, a tertiary referral center. PATIENTS: A mother and both her sons had very early-onset gigantism associated with high levels of serum GH and prolactin. INTERVENTIONS: The condition was treated by total hypophysectomy. MAIN OUTCOME MEASURE(S): We performed clinical, pathological, and molecular evaluations, including evaluation basal and provocative endocrine testing, neuroradiological assessment, and assessment of the pituitary tissue by microscopic evaluation, immunohistochemistry, and electron microscopy. RESULTS: All three family members had very early onset of gigantism associated with abnormally high serum levels of GH and prolactin. Serum GHRH levels were not elevated in either of the boys. The clinical, radiographic, surgical, and histological findings indicated mammosomatotroph hyperplasia. The pituitary gland of both boys revealed diffuse mammosomatotroph hyperplasia of the entire pituitary gland without evidence of adenoma. Prolactin and GH were secreted by the same cells within the same secretory granules. Western blot and immunohistochemistry demonstrated expression of GHRH in clusters of cells distributed throughout the hyperplastic pituitary of both boys. CONCLUSIONS: This hereditary condition seems to be a result of embryonic pituitary maldevelopment with retention and expansion of the mammosomatotrophs. The findings suggest that it is caused by paracrine or autocrine pituitary GHRH secretion during pituitary development.

Macrodystrophia lipomatosa with syndactyly.

Macrodystrophia lipomatosa (MDL) is a rare form of congenital localized gigantism characterized by hypertrophy of all mesenchymal tissues of the affected digits, with particular overgrowth of fat. Syndactyly is a rare association. We report a case of MDL associated with syndactyly affecting the hand. We describe the characteristic radiographic and MRI findings that distinguish the abnormality from other causes of localized gigantism.

Macrodystrophia lipomatosa: macrodactyly related to affected nerves, and a review of the literature.

Macrodystrophia lipomatosa (ML) is a rare disease causing congenital local gigantism of part of an extremity mostly through proliferation of fibro-adipose tissue. This study is one of few that specifically describe 8 ML patients with histological confirmation of the diagnosis combined with the 79 histologically confirmed cases already described in the literature. The goals of this study are to describe this malformation by using only histologically confirmed cases, to offer some insight on current opinions on ML by reviewing the histologically confirmed cases described in the literature, and to make the postulation of autonomic nerve dysfunction as the aetiology of ML more plausible.

Macrodystrophia lipomatosa. MR imaging in three patients.

Radiographs and magnetic resonance (MR) imaging of three patients with macrodystrophia lipomatosa are presented. Radiographs of involved extremities and digits demonstrated prominent soft tissues and bony hypertrophy. MR images showed hypertrophy of fatty tissue, cortical bone thickening and fatty infiltration of muscle.

Language and behavior in children with Sotos syndrome.

OBJECTIVE: To examine language and behavior in children with Sotos syndrome, an overgrowth syndrome involving advanced bone age, characteristic facies, and developmental disability. METHOD: Twenty-seven children with Sotos syndrome were compared with 20 children with overgrowth, intellectual disability, and facies not characteristic of Sotos syndrome. Ages ranged from 5 to 16 years. Direct assessment was undertaken with standardized measures of intelligence and language abilities. Behavior was examined by parent and teacher report. RESULTS: Children with Sotos syndrome had levels of intelligence in the severely disabled to average range, with the majority falling in the borderline range. Mean level of intelligence was significantly higher than that observed for children in the comparison group. Language abilities were developed to a level consistent with overall level of intelligence. Rates of parent- and teacher-reported behavior problems were significantly higher than normal, but, with the exception of temper tantrums, did not differ from those observed in children in the comparison group. Attention-deficit hyperactivity disorder was observed in 38% of children with Sotos syndrome. They were more irritable and had more stereotypic behavior and inappropriate speech than is expected in children with intellectual disabilities, and they were more withdrawn and had more stereotypic behavior than children in the comparison group. CONCLUSIONS: Assessment of language abilities revealed no specific language impairment. High rates of behavior problems were observed, but these were not higher than those observed for other large, delayed, dysmorphic children.

Metacarpophalangeal pattern profile analysis in Sotos and Marfan syndrome.

Patients with Sotos and Marfan syndrome have unusually long metacarpals and phalanges which may make the differential diagnosis difficult in younger children. Using Q-scores, we compared metacarpophalangeal pattern profile (MCPP) analysis in these two syndromes and identified distinct and different pattern profiles. This illustrates that the MCPPs are specific in these syndromes, even at an early age, and not related solely to the unusually long metacarpals and phalanges. For this study we used data from 50 Sotos patients (34 from the United Kingdom and 16 from the Netherlands, with a total of 95 hand films) and 36 Marfan patients (from the Netherlands, with 98 hand films). Of all patients over age 3 years the bone length (including the epiphysis) was determined. The patients under 7 1/2 years (29 Sotos and 12 Marfan) were also measured without inclusion of the epiphysis. The patients measured without epiphysis had a relative short metacarpal 1 (MC1) and long distal phalanx 1 (DPh1) in Sotos syndrome, and a relative long MC1 and short DPh1 in Marfan syndrome. Between age 3 and 7 1/2 years more than 90% of the films could be classified correctly using these two variables. Of the roentgenograms measured with epiphyses, about 80% were classified correctly.

Ocular manifestations of Sotos syndrome.

BACKGROUND: Sotos syndrome (cerebral gigantism) is a congenital syndrome characterized by large body size for patient age, advanced bone age, and unusual facial characteristics with varying levels of cognitive, developmental and perceptual deficits. While more than 150 cases have been reported, only a single case report has been published in the ophthalmic literature. This study briefly reviews the pertinent aspects of this syndrome and reports on the medical, physical, developmental and ocular manifestations of 32 subjects. METHODS: Our patient population was obtained from several schools and colleges of optometry and private offices and clinics of optometrists and ophthalmologists. The Sotos Syndrome Support Association assisted in obtaining patients for this study as well. All children had been previously diagnosed as having SS. Commonly accepted methods for evaluating young, non-verbal, and/or handicapped children were used. RESULTS: Our findings indicate that moderate to high refractive error (hyperopia), nystagmus, and strabismus (esotropia) are commonly associated conditions of this syndrome. CONCLUSIONS: Since many of our subjects exhibited these amblyogenic precursors, a routine optometric vision evaluation should be an essential part of the individual educational and habilitation plan for all children with Sotos syndrome.

Congenital gigantism due to growth hormone-releasing hormone excess and pituitary hyperplasia with adenomatous transformation.

The cause of gigantism in most patients is a GH-secreting pituitary tumor. In this report, a case of congenital gigantism due to probable central hypersection of GH-releasing hormone (GHRH) is described. Normal at birth (4.4 kg; 53 cm), our 7-yr-old male patient grew progressively thereafter to attain a height of 182 cm and a weight of 99.4 kg at the time of our evaluation. The markedly increased baseline plasma levels of GH (730 micrograms/L) did not suppress during a standard 3-h oral glucose tolerance test, but did increase 54% after iv infusion of GHRH. Baseline plasma levels of insulin-like growth factor-I, PRL, and immunoreactive GHRH were also markedly increased. Computed imaging of the head showed a large, partially cystic sellar and suprasellar mass. Extensive imaging studies did not localize a potential source of GHRH. Preoperative treatment with octreotide and bromocriptine for 4 months resulted in a 25% reduction of suprasellar tissue mass. The pituitary tissue removed at transsphenoidal and transfrontal operations showed massive somatotroph, lactotroph, and mammosomatotroph hyperplasia. Areas of GH- and PRL-secreting cell adenomatous transformation were also evident. No histological or immunohistochemical evidence of a pituitary source of GHRH was found. The peripheral plasma immunoreactive GHRH concentration remained unaffected by pharmacological and surgical interventions. We suspect that a congenital hypothalamic regulatory defect may be responsible for the GHRH excess in this case.

Congenital hemihypertrophy.

We present an isolated complete left hemihypertrophy in a girl with follow-up data from birth up to the age of 5 months.

Macrodystrophia lipomatosa: radiographic observations.

23 cases of macrodystrophia lipomatosa (MDL) are reported showing a wide spectrum of radiographic findings. Typical findings were hypertrophy of all the mesodermal tissues of the affected digits with dramatic overgrowth of fat. Phalanges were enlarged both in length and transverse diameter, but the trabecular pattern was maintained. In one patient, the phalanges and metatarsals were elongated but thinned. In another case, all the phalanges and metatarsals of the great toe were small. The little toe was also involved in two cases. Articular surfaces were slanting. There was a high incidence of palmar and plantar involvement. In a few cases the forearm and leg were also involved. Other uncommon features observed were early maturation of epiphyseal centres of ossification of phalanges and metatarsals, syndactyly, polydactyly, brachydactyly and symphalangism. Angiography was uncharacteristic.

A new operative technique for congenital gigantism of the toes.

A technique for reducing congenital gigantism of the toes which has been used successfully in four patients is described.

In utero diagnosis of benign fetal macrocephaly.

Benign familial macrocephaly is an autosomal dominant disorder associated with a large absolute circumference of the head. In this disorder serial growth demonstrates a proportional rather than an excessive rate of growth. To date, we are not aware of any published case reports that confirm the diagnosis prenatally. We report a case of benign familial macrocephaly diagnosed in utero by ultrasonographic evaluation. This case report points out the necessity of combining appropriate family history and physical examination in cases of prenatally detected anomalies.

Adrenocortical carcinoma in a child with congenital hemihypertrophy.

We describe a very rare case of adrenocortical carcinoma (ACC) presenting with Cushing's virilising syndrome in a female child with congenital hemihypertrophy (CHh). CHh was of more value for early detection of ACC than Cushing's virilisation.