Sporadic case of trichorhinophalangeal syndrome type III in a European patient.

Trichorhinophalangeal syndrome type III (TRP III) shares common traits with TRP I and II, including sparse hair, a "pear-shaped" nose, osteodysplasia with cone-shaped epiphyses, and autosomal dominant inheritance, but is distinguished by the presence of severe brachydactyly. TRP III was first described in 1984 in Japanese patients, one sporadic case [Sugio and Kajii, 1984: Am. J. Med. Genet. 19:741-753,1984] and two families [Niikawa and Kamei, 1986: Am. J. Med. Genet. 24:759-760; Naga? et al., 1994: Am. J. Med. Genet. 49:278-280], and more recently in a Turkish family [Itin et al., 1996: Dermatology 193:349-352]. We report an additional observation in a patient of European descent, who presented with short stature, cone-shaped epiphyses, sparse hair, a pear-shaped nose, normal intelligence and severe brachydactyly. Neither parent had manifestations of TRP and there was no other reported case in the family, indicating a presumably fresh mutation. Our observation refines the clinical spectrum of TRP III in another ethnic background and may be of help in identifying the gene or genes for TRP syndromes.     

Confirmation of the colobomatous macrophthalmia with microcornea syndrome: Report of another family

We report on the occurence of microcornea, coloboma, and macrophthalmia in 4 generations of an Italian family. The patients had no additional physical anomalies, were of normal intelligence, and had a normal karyotype. This condition has been reported in only 1 family [Bateman and Maumenee, 1984: Ophthalmol Pediatr Genet 4:59–66]. The recurrence of this distinctive ocular pattern in our opinion confirms the existence of a new syndrome, with autosomal dominant inheritance. Am. J. Med. Genet. 76:252–254, 1998. © 1998 Wiley-Liss, Inc.     

A family with Duane anomaly and distal limb abnormalities: a further family with the arthrogryposis-ophthalmoplegia syndrome

A two-generation family is reported in which three members have Duane anomaly and distal limb abnormalities. All three affected have photopic electroretinogram responses that are abnormal or at the lower limit of the normal range with normal scotopic responses. Two affected family members also have hearing loss. The likeliest diagnosis is the syndrome listed as "arthrogryposis-ophthalmoplegia syndrome" on the London Dysmorphology Database or as "arthrogryposis with oculomotor limitation and electroretinal abnormalities" or "oculomelic aplasia" in OMIM [MIM 108145]. In view of the similarities with Okihiro syndrome, a search for mutations within the SALL4 gene was undertaken, but none were identified.     

Sonographic Assessment of Renal Growth in Patients with Beckwith-Wiedemann Syndrome: The Beckwith-Wiedemann Syndrome Renal Nomogram

BACKGROUND:

Beckwith-Wiedemann syndrome is a disorder of somatic overgrowth. Evidence of kidney overgrowth is a diagnostic criterion that may be used to help identify those patients who are at the greatest risk of developing Wilms tumors. In such subjects, kidney size is typically larger than that of age-matched normal controls.

OBJECTIVE:

The purpose of our study was to generate a nomogram that could be used to measure renal dimensions in children with Beckwith-Wiedemann syndrome in a clinical setting.

MATERIALS & METHODS:

All of the Beckwith-Wiedemann syndrome patients followed at our institution from 1996 to 2004 were eligible for inclusion in our study. Renal length was measured with a curvilinear transducer and with the patient supine. Renal lengths were measured for both kidneys using real-time ultrasound for all patients. Their data were compared with those of age-matched controls reported in the 1984 study by Rosenbaum et al.

RESULTS:

Ninety-six children with Beckwith-Wiedemann syndrome were followed from 1996 to 2004. Forty-three of these patients met our criteria for inclusion in the study: 28 girls (65%) and 15 boys (35%). We identified a linear relationship between kidney length and patient age. No statistically significant differences in renal length were found between boys and girls (p=0.2153) or between the kidneys on either side of the body (p=0.9613).

CONCLUSION:

Our study provides a practical, simple renal growth chart that offers a reasonable, sensitive method for evaluating kidney size in children with Beckwith-Wiedemann syndrome.     

The Golabi-Rosen syndrome--report of a second family

Golabi and Rosen (1984) have reported on a new X-linked mental retardation/multiple congenital anomalies (XLMR/MCA) syndrome of pre- and postnatal overgrowth, characteristic "coarse" facial appearance with macrostomia, midline groove of tongue, lower alveolar ridge and lip, submucous cleft of palate, supernumerary nipples, intestinal anomalies, supernumerary pair of ribs, anomalies of sacrum and tailbone, hypoplastic index fingernails, postaxial polydactyly and other digital anomalies. This was an incompletely recessive trait with some manifestations evident in an obligatory carrier. Here we report on a second family (studied at the University of Wisconsin for over 9 years) in which 3 males born to half-sisters and their mother were affected with the Golabi-Rosen syndrome (GRS). Overgrowth was not a prominent manifestation in these affected males. Presence of cystic kidneys, peculiar skin changes and hepatomegaly make it likely that the Golabi-Rosen syndrome is an X-linked MCA/dysplasia/MR syndrome. Its metabolic basis remains unknown. It seems to be an incompletely recessive trait.     

Diagnosis of chromosome 3 duplication q23----qter, deletion p25----pter in a patient with the C (trigonocephaly) syndrome

The cells of a deceased patient previously reported to have the C (trigonocephaly) syndrome were reinvestigated because his phenotype resembled that of a patient with a duplication-deficiency of chromosome 3. This diagnosis was confirmed using fibroblasts grown from frozen cells, and his mother was shown to carry an inversion of chromosome 3 in her peripheral blood leukocytes. His findings are compared to those of another patient with the C trigonocephaly syndrome with normal chromosomes and to others from the literature. At least one other patient from the literature has a phenotype compatible with "3q duplication syndrome."     

Choanal stenosis,hypothelia, deafness,recurrent dacryocystitis,neck fistulas,short stature,and microcephaly: report of a case

We report on a 11-year-old girl with bilateral choanal stenosis, hypothelia, hearing loss, recurrent dacryocystitis, neck fistulas, short stature, and microcephaly. Only three individuals with choanal atresia from a consanguineous family have been reported. One of the patients also had hypoplastic nipples, hypotonia, and delay in speech development. Similar clinical features were seen in two children reported by Greenberg [1987: Am J Med Genet 28:931-934] and Wilson et al. [1998: Am J Med Genet 75:220-222]. They were prenatally exposed to methimazole because of maternal Graves disease. Neck fistulas and microcephaly noted in our patient were not previously reported as features of the syndrome or in the patients prenataly exposed to methimazole. Our patient and those reported by Qazi et al. [1982: Am J Med Genet 13:413-416] most probably have a rare syndrome characterized by this distinctive combination of symptoms. Prenatal exposure to methimazole can cause a phenocopy of the syndrome, which was probably the case in the patients reported by Greenberg and Wilson et al.     

Secondary acute myeloblastic leukemia with a Ph translocation in a treated Wegener's granulomatosis

Ph-positive acute myeloblastic leukemia (AML) developing in a treated case of Wegener's granulomatosis is reported. The patient was a 70-year-old white male who received cyclophosphamide (150 mg/day) starting in July 1978; in May 1984 the patient was diagnosed as having AML, following a diagnosis of myelodysplastic syndrome lasting 3 months. Cytogenetic study of bone marrow cells at the diagnosis of the myelodysplastic syndrome revealed a standard Ph translocation in addition to numerical chromosome changes [i.e., 45,XY, -5, -7, -8, +19, +mar/45,XY, -5, -7, -8, +19, +mar,t(9;22)(q34;q11]). The events in this case suggest a strong possibility of the Ph-positive AML being a secondary disease related to prior cyclophosphamide therapy.     

Dup(3)(p2----pter) in two families, including one infant with cyclopia

We report on 2 unrelated cases of duplication of distal 3p due to balanced maternal translocation t(3;6)(p23;q27) and t(2;3)(p25;p23) respectively. One family was ascertained through the unbalanced offspring and the other through echographic examination of the balanced carrier mother. These cases confirm that dup(3)(p2----pter) results in a characteristic syndrome with distinctive facial appearance. In family 2 inspection of a photograph of a deceased sib was sufficient to conclude that he was affected. The patient in family 2 had cyclopia. Since holoprosencephaly was also reported by Martin and Steinberg [1983], we conclude that this anomaly appears to be a sign of the syndrome. The duplication usually derives from a maternal balanced translocation, in most cases from adjacent-1 segregation. However, family 2 was ascertained through a balanced female carrier who inherited the translocation from the father. We have noted that the second chromosome (which varies without apparent preferences) involved in these translocations is broken consistently at a distal band.     

Dup(3)(p2→pter) in two families,including one infant with cyclopia

We report on 2 unrelated cases of duplication of distal 3p due to balanced maternal translocation t(3;6)(p23;q27) and t(2;3)(p25;p23) respectively. One family was ascertained through the unbalanced offspring and the other through echographic examination of the balanced carrier mother. These cases confirm that dup(3)(p2→pter) results in a characteristic syndrome with distinctive facial appearance. In family 2 inspection of a photograph of a deceased sib was sufficient to connclude that he was affected. The patient in family 2 had cyclopia. Since holoprosencephaly was also reported by Martin and Steinberg [1983], we conclude that this anomaly appears to be a sign of the syndrome. The duplication usually derives from a maternal balanced translocation, in most cases from adjacent-1 segregation. However, family 2 was ascertained through a balanced female carrier who inherited the translocation from the father. We have noted that the second chromosome (which varies without apparent preferences) involved in these translocations is broken consistently at a distal band.     

Clinical delineation of Giuffrè-Tsukahara syndrome: another case with microcephaly and radio-ulnar synostosis with apparent X-linked semi-dominant inheritance

Two families and three sporadic cases have been described so far with the combination of radio-ulnar synostosis and microcephaly as main features. Some authors have discussed whether the first family reported by Giuffrè et al. [1994] and the second family described by Tsukahara et al. [1995] had the same syndrome. Although there is phenotypic variability among the described cases (especially with respect to facial dysmorphisms and mental retardation), the clinical patterns do not seem to be clearly distinguishable from each other. We describe another family with apparent X-linked semi-dominant inheritance with milder features in the female patient due to skewed X-inactivation. From a clinical synopsis, we consider the Giuffrè-Tsukahara syndrome as one genetic entity, which is characterized by the association of microcephaly and radio-ulnar synostosis, mental retardation in male patients and variable minor features. Patients with the Giuffrè-Tsukahara syndrome do not present with a characteristic pattern of facial features.     

Patterns of family communication and preferred resources for sharing information among families with a Lynch syndrome diagnosis

Objectives

To explore patterns of communication among families with a Lynch syndrome diagnosis and understand what resources could facilitate family communication.

Simpson-Golabi-Behmel syndrome: an X-linked encephalo-tropho-schisis syndrome

We report on another family with the so-called "gigantism-dysplasia syndrome", an X-linked condition characterized by pre- and postnatal overgrowth, characteristic face with apparent coarseness, dysplastic changes in several tissues, and mild intellectual impairment. This condition has been called the Golabi-Rosen syndrome; however, we agree that is the same entity as that described, in a milder form, by Simpson et al in 1975 and by Behmel et al in 1984. Therefore, we suggest that this entity be designated the Simpson-Golabi-Behmel syndrome. The manifestations in affected individuals suggest that this condition represents an X-linked encephalo-tropho-schisis syndrome.     

Excessive hypernatremia in a patient with renal amyloid disease

Summary A 24-year-old Italian male presented with a nephrotic syndrome in September 1984. In February 1985 renal biopsy showed amyloid disease with tubular atrophy and interstitial fibrosis. Edema was treated with furosemide, and cholchicine was started. Because he feared side effects of drug therapy, the patient stopped all medication by July 1985. Instead, he decided to restrict severely fluids in order to fight edema. In early November 1985 his family noted he was becoming increasingly lethargic. Two weeks later, on his admission to the hospital, he had a serum sodium concentration of 193 mmol/l and serum osmolality of 397 mosm/kg. Apart from mild mental status changes neurological examination was normal. The fluid deficit was slowly corrected. He was discharged three weeks later with normal serum electrolytes. This case demonstrates that (1) severe hypernatremia can present with mild neurological symptoms and (2) it can be survived provided that it develops slowly and is corrected cautiously.     

Delineation of a newly recognized neurocutaneous malformation syndrome with "cutis tricolor"

The term "cutis tricolor" describes the combination of congenital hyper- and hypo-pigmented lesions, in close proximity to each other with a background of normal skin. Cutis tricolor represents twin spotting and has been reported as an isolated skin disorder or as part of a neurocutaneous malformation syndrome. We report on an 11-year-old girl with diffuse pigmentary changes of the cutis tricolor type, facial anomalies, mental retardation, epileptic seizures, EEG anomalies, small skull, progressive double-curved thoracolumbar/lumbar scoliosis with vertebral scalloping and dysplastic vertebral pedicles and ribs, and tibial bowing. These abnormalities are similar to those observed in cases reported by Happle et al. [1997: J Med Genet 34:676-678] and Ruggieri [2000: Eur J Pediatr 159:745-749]. Additionally, our patient had altered behavior and hypoplasia of the corpus callosum. This constellation of abnormalities represents a newly recognized neurocutaneous malformation syndrome. The phenotype could be explained by somatic mutation. Loss of heterozygosity at an early developmental stage would give rise to one single mosaic skin disorder (e.g., generalized skin manifestations of the cutis tricolor type in association to extracutaneous anomalies). Postzygotic recombination occurring later during embryogenesis would give rise to solitary lesions confined to the skin.     

Autosomal recessive syndrome of sacral and conotruncal developmental field defects (Kousseff syndrome)

Kousseff [1984] reported on three sibs with an autosomal recessive syndrome of sacral meningocele, conotruncal heart defects, and minor anomalies of head and neck. We report on a fourth case and discuss the findings from a developmental field perspective and the ramifications for genetic counseling.     

Congenital scalp defects and vitreoretinal degeneration: Redefining the Knobloch syndrome

An apparently autosomal recessive syndrome of hereditary vitreoretinal degeneration (VRD) with retinal detachment, high myopia, and congenital encephalocele was described in 1971 by Knobloch and Layer [J Pediatr Ophthalmol 8:181–184]. Clinical confirmation of the presence of encephaloceles was lacking, and no neuropathologic studies were reported. We have evaluated a similarly affected family with 2 sibs with high myopia, VRD, and occipital scalp defects. Histologic examination of the scalp defects showed heterotopic neuronal tissue in both instances. The older girl has had a unilateral retinal detachment. Her other eye and both eyes of the younger sib have so far been treated successfully with prophylactic retinal cryotherapy. Both children have normal to above normal intelligence. The family reported by Knoblock and Lyer [1971] and the sibship herein described appear to represent a distinct autosomal recessive trait. Analysis of the associated defects suggests an underlying defect in early cephalic neuroectodermal morphogeneis. Data from these families imply that congenital occipital scalp defects rather than true encephaloceles may, as is true in some cases of Meckel syndrome, accompany Knobloch syndrome. The presence of a congenital midline scalp defect should alert the clinician to possible underlying central nervous system and/or ocular pathology and should lead to consideration of further diagnostic evaluations And prophylactic measures. © 1993 Wiley-Liss, Inc.