Caroline Crachami, the Sicilian Fairy: a case of bird-headed dwarfism.

One of the most remarkable cases of extreme dwarfism on record is Caroline Crachami, the Sicilian Fairy. She was born in 1815, and was taken to London to be exhibited for money in 1824. Due to her proportional dwarfism, severe intrauterine growth retardation, and typical "bird-headed" profile, Caroline Crachami has by some been diagnosed as a case of the autosomal recessive Seckel syndrome. In this historical vignette, the Sicilian Fairy's life and death are presented in some detail using new material, and the problem of her correct diagnosis is discussed.     

Caroline crachami,the sicilian fairy: A case of bird-headed dwarfism

One of the most remarkable cases of extreme dwarfism on record is Caroline Crachami, the Sicilian Fairy. She was born in 1815, and was taken to London to be exhibited for money in 1824. Due to her proportional dwarfism, severe intrauterine growth retardation, and typical “bird-headed” profile, Caroline Crachami has by some been diagnosed as a case of the autosomal recessive Seckel syndrome. In this historical vignette, the Sicilian Fairy's life and death are presented in some detail using new material, and the problem of her correct diagnosis is discussed. © 1992 Wiley-Liss, Inc.     

A new Seckel-like syndrome of primordial dwarfism

Seckel syndrome is a rare, recessively inherited disorder of severe growth retardation and distinct craniofacial, orodental, and skeletal anomalies. Even though there are well-established minimum diagnostic criteria for this syndrome, controversy exists about its boundaries and criteria for exclusion. We studied 2 remarkably similar, unrelated children with most of the clinical and radiographic manifestations of Seckel's original patient. Although their craniofacial and orodental anomalies are typical of Seckel syndrome, 1 child has unusual appearance of the hands and feet that have not been previously associated with it. This patient appears to define a new Seckel-like syndrome and suggests heterogeneity in this type of primordial dwarfism. © 1996 Wiley-Liss, Inc.     

Congenital hypoparathyroidism, seizure, extreme growth failure with developmental delay and dysmorphic features—another case of this new syndrome

A 4-year-old Saudi female child with extreme failure to thrive, striking dysmorphic features, developmental delay, congenital hypoparathyroidism, UTI, seizures, chronic otitis media, chronic non-specific gastroenteritis and repeated life-threatening infections was followed from birth. She was the product of first-cousin consanguineous marriage. She had striking facies with frontal prominence, deep-set eyes, depressed nasal bridge, beaked nose, long philtrum with thin upper lip, micrognathia, large floppy ears, bifid uvula, and growth retardation with SD score less than -2 for height, weight and head circumference. We believe these features which include congenital hypoparathyroidism, severe growth failure and developmental delay in the absence of chromosomal abnormality represent a newly described genetically determined syndrome.     

Fetal biometry in the Brachmann-de Lange syndrome

The Brachmann-de Lange syndrome (BDLS) is diagnosed in children on the basis of a distinctive clinical phenotype which includes retarded physical growth. Because there are no genetic or biochemical tests at present, the antenatal detection of the syndrome may depend upon identification of some aspect of the phenotype in the fetus using ultrasound imaging. We studied the growth of 23 subsequently diagnosed fetuses with the BDLS using standard biometric parameters defined by prenatal ultrasound imaging. Sonographic studies were obtained through a national parents' group, the Cornelia de Lange Syndrome Foundation. Assessment of fetal growth was made using four standardized measurements: the biparietal diameter, head circumference, femur length, and abdominal circumference. These values were compared to established tables of normal fetal growth and established rations of fetal body proportions. The cross-sectional growth curve derived using all measurements collected as a composite group indicates that growth retardation would be first detected as early as 25 weeks. In five fetuses with measurements both before and after 25 weeks of gestation, longitudinal growth curves indicated that the diagnosis of “small for gestational age” would have been suggested between 20 and 25 weeks. The mean fetal weight estimates closely followed the fifth centile curve of normal fetuses both before and after 25 weeks. Cephalic indices in BDLS fetuses indicated either frank brachycephaly (25%), or were at the upper portion of the normal range. Femur lengths were relatively short (less than 90% of their expected length ) in 4 of the 11 fetuses where such information could be obtained. BDLS fetuses demonstrate early and symmetric intrauterine growth retardation. We conclude that fetal biometry can provide a valuable index in the assessment of a pregnancy suspected to be at risk for a severely affected BDLS child. © 1993 Wiley-Liss, Inc.     

Interstitial deletion 2q33.3-q34 in a boy with a phenotype resembling the Seckel syndrome

A boy presented at 5 weeks with a syndrome of pre- and postnatal growth retardation, microcephaly, muscular hypotonia, and facial anomalies resembling those seen in Seckel syndrome or microcephalic primordial dwarfism I. Analysis of prometaphase chromosomes, fluorescent in situ hybridization (FISH), and molecular studies showed the presence of a de novo chromosome 2 deletion that could be defined as del(2)(q33.3q34)pat. Parental chromosomes were normal, except for the presence of a paternal supernumerary marker identified by FISH as der(15). On follow-up of the patient during the next months length development appeared normal and the diagnosis of Seckel syndrome was withdrawn. Clinical findings of previously published cases with interstitial deletion of at least 2q33.3-q34, the deletion present in the propositus, are reviewed and include pre- and postnatal growth retardation, psychomotor retardation, microcephaly, micrognathia, and abnormal/low-set ears; findings also present in the propositus. These findings resemble those described in the Seckel syndrome. Noteworthy is the finding that 2/3 of the 60 reviewed cases originally reported as having Seckel syndrome apparently belong to a heterogeneous group of low birth weight microcephalic dwarfism I yet to be clearly defined. In these patients no chromosome 2q deletion has been reported so far. Retrospective analysis could show if a subgroup of these patients carry submicroscopic deletions at 2q33.3-q34. Alternatively, molecular analysis of this region may be warranted in newly diagnosed patients with Seckel syndrome- like manifestations. Am. J. Med. Genet. 71:479–485, 1997. © 1997 Wiley-Liss, Inc.     

Craniotubular dysplasia with severe postnatal growth retardation,mental retardation,ectodermal dysplasia,and loose skin: Lenz-Majewski-Like syndrome

The heterogeneous group of craniotubular dysplasias is characterized by modeling errors of the craniofacial and tubular bones. Some conditions in this category cause not only skeletal abnormalities but also a variety of mesoectodermal dysplasias, as exemplified in Lenz-Majewski syndrome (MIM 151050), which comprises craniodiaphyseal dysplasia, failure to thrive, mental retardation, proximal symphalangism, enamel hypoplasia, and loose skin. We report on a boy with a hitherto unknown multisystem disorder, including skeletal changes that were regarded as a form of craniotubular dysplasia. The patient had a large head, exophthalmos, a broad nasal root, anteverted nostrils, large auricles, thick lips, micrognathia, severe postnatal growth retardation with emaciation, severe mental retardation, sparse hair growth, enamel hypoplasia, and thin, loose skin with hyperlaxity. Skeletal changes consisted of thickened calvaria, sclerosis of the skull base and facial bones, thick ribs, and metaphyseal undermodeling of the tubular bones. In addition, generalized osteopenia was evident. The present disorder overlaps phenotypically with Lenz-Majewski syndrome; nevertheless, the absence of diaphyseal hyperostosis and proximal symphalangism in the present patient was not consistent with Lenz-Majewski syndrome. Am. J. Med. Genet. 71:87–92, 1997. © 1997 Wiley-Liss, Inc.     

A syndrome with multiple malformations, mental retardation, and ACTH deficiency

We report on a patient with severe pre- and post-natal growth retardation, moderate mental retardation, microcephaly, unusual face with marked micrognathia and cleft palate, minor skeletal abnormalities, atrioseptal defect, hypospadias, hearing loss, and secondary adrenal insufficiency due to isolated ACTH deficiency diagnosed at 7 years of age. Family history was negative. Adrenal insufficiency is an uncommon feature in multiple malformation syndromes and may thus serve as a diagnostic handle for recognizing other possible patients with a similar syndrome.     

How necessary is a chromosomal analysis in growth-retarded girls?

In growth-retarded girls, shortness may be the only clinical sign of Turner syndrome. Therefore recommendations have been published that a chromosomal analysis should be carried out in every girl showing growth retardation. The present study was carried out to examine whether the head circumference of small girls can serve as a criterion and hence limit the need for expensive chromosomal analysis. The head circumferences of 45 girls with Turner syndrome were compared with those of 41 growth-retarded girls. It could be shown that the heads of the patients with Turner syndrome had a normal circumference, whereas the heads of the control group were significantly smaller. In view of this result, the risk of overlooking Turner syndrome in diagnosing growth retardation without a chromosomal analysis could be estimated to be 1:9000. The conclusion is drawn that a chromosomal analysis is not necessary in girls whose growth retardation is combined with a small head circumference and who do not show other malformations.     

Cockayne syndrome: the developing phenotype

Cockayne syndrome is a rare autosomal recessive condition comprising microcephaly, "cachectic dwarfism" and progressive neurological degeneration. We present a 21-year-old woman who was not diagnosed with Cockayne syndrome type I until she was 21 years old. Family photographs demonstrated that the phenotype of Cockayne syndrome did not become evident until she was 8 years old. She had severe microcephaly, micrognathia, protruding ears, dental overcrowding with caries, progressive spastic quadriparesis, and severe developmental regression. Her head computed tomography (CT) showed bilateral calcification of the globus pallidus and global atrophy. The purpose of this clinical report is to alert clinicians to the fact that the phenotypic features of Cockayne syndrome may be very subtle early in the course of the disease.     

A new syndrome of dwarfism, brachydactyly, nail dysplasia, and mental retardation in sibs

We describe a new multiple congenital anomaly/mental retardation (MCA/MR) syndrome in chromosomally normal sibs. Both had microcephaly, a "coarse" face with synophrys, ear anomalies, type B brachydactyly, nail dysplasia, skeletal anomalies, dwarfism, and mental retardation. Their mother had nail dysplasia, mild mental retardation, and short stature. An uncle, a younger brother of the mother, died at 17 years of age and also had a "coarse" face, digital anomalies, dwarfism, and severe mental retardation. The malformation complex in this family apparently has not been described previously, and the manifestations of the patients do not correspond to those of any known malformation syndrome. The disorder may be attributable to the pleiotropic effect of an autosomal dominant or an X-linked semidominant gene.     

A lethal autosomal recessive syndrome of multiple congenital contractures

We describe 16 cases of a lethal syndrome with multiple congenital contractures from ten families. The main clinical findings included intrauterine growth retardation with marked fetal hydrops, multiple contractures, and facial abnormalities, especially micrognathia. At autopsy, pulmonary hypoplasia and muscular atrophy were present. There was a paucity of anterior horn motor neurons in the four studied cases. We think that the cases represent the same clinical entity, probably caused by homozygosity of an autosomal recessive gene. The syndrome resembles the Pena-Shokeir I syndrome, but seems to differ in some respects, including length of survival and presence of hydrops. Prenatal diagnosis of this syndrome is possible after the 16th week of pregnancy with ultrasound.     

Third case of Pfeiffer-type cardiocranial syndrome

We report on a third child with a newly recognized craniosynostosis syndrome involving the sagittal suture. Additional findings not related to the abnormal head growth include micrognathia with limited mouth opening, tracheobronchial anomalies, congenital heart defects, microphallus, cryptorchidism, and growth and mental retardation.     

Dup(lq)(q42→qter) syndrome: Case report and review of literature

We report on a patient with primordial growth retardation, mental retardation, and minor anomalies (triangular face, open sagittal suture, frontal bossing, telecanthus, upturned nose, micrognathia, and small mouth with downturned corners). The diagnosis of Russell-Silver syndrome (RSS) had been considered but was abandoned when cytogenetic evaluation showed a partial trisomy lq or duplication lq (46,XY,15, + der(15)t(l;15)(q42;qter). Data from another 5 reports of dup(l)(q42→qter) do not allow delineation of a typical syndrome. However, individuals with dup(lq), del(15q), and Russell-Silver syndrome share common manifestations (i.e., low birth weight, growth retardation, triangular face, low set/abnormal ears, micrognathia, renal anomalies). © 1993 Wiley-Liss, Inc.     

Two sibs with Wiedemann-Rautenstrauch syndrome: possibilities of prenatal diagnosis by ultrasound.

A girl with Wiedemann-Rautenstrauch syndrome was born to a non-consanguineous couple. During the pregnancy, growth retardation particularly in the biparietal and abdominal diameters but not the femoral length was detected through serial ultrasound scans. When the woman became pregnant again, in spite of having been assessed as having a 25% risk of recurrence, the prenatal findings seen in her previous pregnancy led us to suggest sequential echography and a similar pattern of growth retardation was shown. After termination, the male fetus was found to be affected by Wiedemann-Rautenstrauch syndrome. This case shows that ultrasound examination can be a useful tool in the prenatal diagnosis of this rare, autosomal recessive syndrome.     

The Borjeson-Fbrssman-Lehmann syndrome

The propositus of this report presents a peculiar dysmorphic syndrome associated with severe mental retardation and epileptic attacks. Morphological stigmata include a round, fatty face with large, somewhat protruding tongue, large normally formed ears, relative microcephaly, abundant abdominal fat, dwarfism with hyperkyphosis and short neck. Analogous phenotypic abnormalities were present in the mother and a maternal cousin. The clinical and familial findings in this apparently rare mental retardation syndrome with apparently X-linked dominant or autosomal dominant inheritance with variable expression and penetrance are discussed.     

Craniomicromelic syndrome: first report in a male

We report on craniomicromelic syndrome in a male fetus. This case had the previously reported features of prenatal onset growth retardation, underossified cranial bones, wide sutures and fontanels, small face as compared to head, small palpebral fissures, pinched nose, microstomia, micrognathia, and narrow thorax. The consistent combination of these features with short appearing limbs as observed in this case establishes this syndrome as a distinct entity.     

Interstitial deletion of the long arm of chromosome 4, del(4)(q28→q31.3)

Interstitial deletions of the long arm of chromosome 4 are rare. Different breakpoints are involved. Only one of the patients had a very similar deletion to that of the present case. Both had low birth weight at term; weight, length and head circumference less than the third centile; epicanthic folds; apparently low-set abnormal ears; broad nasal bridge; micrognathia; hypoplastic nails; delayed psychomotor development; and mild mental retardation. © 1995 Wiley-Liss, Inc.     

Toriello-Carey syndrome: Evidence for X-linked inheritance

Toriello-Carey syndrome is characterized by agenesis of the corpus callosum, telecanthus, short palpebral fissures, Robin sequence, abnormal ears, cardiac anomalies, and hypotonia. We describe two patients with Toriello-Carey syndrome and call attention to an unbalanced sex ratio. The first patient, a male, was born at term by Cesarean section and manifests micrognathia, cleft soft palate, hypoplastic right ear, anotia on the left side, cerebellar vermis hypoplasia, hydrocephalus, agenesis of the corpus callosum, and hypoplastic left heart. He died 2 days after birth. The second patient is the male sib of a patient reported previously [Am J Med Genet 42: 374–376; 1992]. He had large fontanelles, telecanthus, a short nose, small and malformed ears, micrognathia, a large ventricular septal defect, and pulmonary stenosis. At age 8 months he has growth retardation and developmental delay. A sister is unaffected. Review documented eight other patients with Toriello-Carey syndrome, six of whom were male. The two female patients are less severely affected and are still alive. Of the other male patients, all are deceased except one who is still alive at age 5 years; he has severe growth retardation (-3 SD), mental retardation (DQ44), severe speech delay, and characteristic anomalies. The predominance of affected males and the milder phenotype in the female patients suggests an X-linked gene or sex influenced gene. © 1996 Wiley-Liss, Inc.