Mandibuloacral dysplasia and LMNA A529V mutation in Turkish patients with severe skeletal changes and absent breast development.

Mandibuloacral dysplasia (MAD) is an autosomal recessive disorder characterized by acroosteolysis (resorption of terminal phalanges), skin changes (hyperpigmentation), clavicular hypoplasia, craniofascial anomalies, a hook nose and prominent eyes, delayed closures of the cranial sutures, lipodystrophy, alopecia, and skeletal anomalies. MAD patients are classified according to lipodystrophy patterns: type A and type B. The vast majority of MAD cases are caused by LMNA gene mutations.

Prenatally diagnosed case of 22q11.2 deletion syndrome associated with pulmonary artery aneurysm.

Here, we report a new case with chromosome 22q11 deletion and cardiac anomaly diagnosed prenatally by echocardiography. Fluorescence in situ hybridization (FISH) analysis demonstrated a heterozygous deletion at 22q11.2.

Familial ring (18) mosaicism in a 23-year-old young adult with 46,XY,r(18) (::p11→q21::)/46,XY karyotype, intellectual disability, motor retardation and single maxillary incisor and in his phenotypically normal mother, karyotype 47,XX,+r(18)(::p11→q21::)/46,XX.

We report on a 23-year-old man with craniofacial findings of the holoprosencephaly spectrum disorder (microcephaly, hypotelorism, depressed nasal bridge, single median maxillary central incisor), fusion of C2-C3 vertebrae, intellectual disability, and severe sleep apnea. Chromosome analysis of blood lymphocytes showed 75% ring (18) cells and 25% normal cells, karyotype mos 46,XY,r(18)(::p11→q21::)[75]/46,XY[25]. His mother was phenotypically normal except for a double ureter and bifid renal pelvis as in his son.

Disruption of ALX1 causes extreme microphthalmia and severe facial clefting: expanding the spectrum of autosomal-recessive ALX-related frontonasal dysplasia.

We present an autosomal-recessive frontonasal dysplasia (FND) characterized by bilateral extreme microphthalmia, bilateral oblique facial cleft, complete cleft palate, hypertelorism, wide nasal bridge with hypoplasia of the ala nasi, and low-set, posteriorly rotated ears in two distinct families. Using Affymetrix 250K SNP array genotyping and homozygosity mapping, we mapped this clinical entity to chromosome 12q21. In one of the families, three siblings were affected, and CNV analysis of the critical region showed a homozygous 3.

Characterization of double ring chromosome 4 mosaicism associated with bilateral hip dislocation, cortical dysgenesis, and epilepsy.

We present the clinical and molecular findings in a Turkish child with a de novo mosaic ring derived from chromosome 4 with multiple cell-lines; the karyotype was 46,XY,r(4)[83]/45,XY, -4[6]/47,XY,r(4),+r(4)[5]/48,XY,r(4),+r(4),+dic r(4)[1]/46,XY[5]. The patient is a 20-month-old male who was the first pregnancy of nonconsanguineous parents. The baby was delivered at term with a birth weight of 1,700 g (<3rd centile) and a length of 46 cm.

A specific mutation in the distant sonic hedgehog (SHH) cis-regulator (ZRS) causes Werner mesomelic syndrome (WMS) while complete ZRS duplications underlie Haas type polysyndactyly and preaxial polydactyly (PPD) with or without triphalangeal thumb.

Werner mesomelic syndrome (WMS) is an autosomal dominant disorder with unknown molecular etiology characterized by hypo- or aplasia of the tibiae in addition to the preaxial polydactyly (PPD) of the hands and feet and/or five-fingered hand with absence of thumbs. We show that point mutations of a specific nucleotide within the sonic hedgehog (SHH) regulatory region (ZRS) cause WMS. In a previously unpublished WMS family, we identified the causative G>A transition at position 404 of the ZRS, and in six affected family members of a second WMS family we found a 404G>C mutation of the ZRS.

Early prenatal diagnosis of conjoined twins at 7 weeks and 6 days' gestation with two-dimensional Doppler ultrasound: a case report.

This case report presents the prenatal diagnosis of conjoined twins at 7 weeks and 6 days' gestation according to the last menstrual period and 6 weeks and 4 days' gestation according to crown-rump length in a 32-year-old Turkish woman, using two-dimensional Doppler ultrasound. The twins were fused to each other at the thoracic region (thoracopagus). In the light of previous reports of conjoined twins this appears to be one of the earliest prenatally diagnosed cases in the medical literature.

A 19-year follow-up of a patient with type 3 ectrodactyly-ectodermal dysplasia-clefting syndrome who developed non-Hodgkin lymphoma.

The ectrodactyly-ectodermal dysplasia-clefting (EEC) syndrome is characterized by ectrodactyly, ectodermal dysplasia, and clefting. The development of a malignancy with EEC syndrome is very rare. Here we present follow-up on a Turkish boy with EEC syndrome type 3 who developed malignant lymphoma with high expression of p63.

ALX4 dysfunction disrupts craniofacial and epidermal development.

Genetic control of craniofacial morphogenesis requires a complex interaction of numerous genes encoding factors essential for patterning and differentiation. We present two Turkish families with a new autosomal recessive frontofacial dysostosis syndrome characterized by total alopecia, a large skull defect, coronal craniosynostosis, hypertelorism, severely depressed nasal bridge and ridge, bifid nasal tip, hypogonadism, callosal body agenesis and mental retardation. Using homozygosity mapping, we mapped the entity to chromosome 11p11.

A well-documented trisomy 13 case presenting with a number of common and uncommon features of the syndrome.

Trisomy 13 is a very rare and lethal autosomal chromosomal malformation syndrome. Its incidence is 1/12,000 births. In this paper, we present a new trisomy 13 case associated with unusual and undescribed findings.

Prenatally diagnosed lethal type Larsen-like syndrome associated with bifid tongue.

Larsen syndrome is characterized by multiple joint dislocations, associated with a typical facial appearance and frequently other abnormalities. Both dominant and recessive patterns of inheritance have been reported. A lethal form of Larsen syndrome (Larsen-like syndrome) has been described as a combination of the Larsen phenotype and pulmonary hypoplasia.

Rubinstein-Taybi syndrome with normal FISH result and CREBBP gene analysis: a case report.

We report on a six-year-old boy with typical Rubinstein-Taybi syndrome (RSTS) phenotype. Clinical findings included mental and motor retardation, patent ductus arteriosus (PDA), undescended testes, hirsutism, broad thumbs with radial angulation and broad toes, and inguinal hernia. His karyotype was normal (46, XY) and fluorescence in situ hybridization (FISH) showed no deletion of the CREBBP [cAMP response element-binding (CREB) binding protein] gene on chromosome 16p13.

Association of assisted reproductive technology with twinning and congenital anomalies.

Recently many reports have been published on the use of intracytoplasmic sperm injection (ICSI) and the increased risk of congenital major malformations or syndromes. We present three cases with Goldenhar syndrome (one of them a twin pair) and one case with Rubinstein-Taybi syndrome (RTS), also a twin pair. All four female cases are derived from ICSI.

Selective feticide in dichorionic pregnancies with intracardiac blood aspiration: report of nine cases.

In a twin pregnancy discordant for a chromosomal or structural abnormality, the family is faced with two alternatives: expectant management or selective feticide of the abnormal fetus. Methods of selective feticide differ according to chorionicity due to the presence of intertwin anastomoses in monochorionic placentas. Intracardiac KCl injection is commonly used in dichorionic pregnancies.

Approach in an adolescent Proteus male patient with megafoot.

Proteus syndrome is a rare overgrowth syndrome characterized by hemihypertrophy, lower limb asymmetry, hyperpigmentations, lipomas, and vascular malformation. In this paper, we present a new adolescent Proteus syndrome patient with bilateral megafoot. He was very successful in playing football and was very popular among his friends.

Complex conotruncal cardiac anomalies consecutively in three siblings from a consanguineous family possibly associated with maternal hyperhomocysteinemia.

Introduction: Conotruncal defects represent an anatomically heterogeneous group of cardiac malformations affecting the outflow tract of the ventricles and the arterial pole of the heart. The exact etiology of congenital heart diseases is unknown.

Case Report: A 31-year-old woman who had three offspring with complex conotruncal cardiac anomalies after consanguineous marriage was reported.

Aberrant splicing is a common mutational mechanism in MKS1, a key player in Meckel-Gruber syndrome.

Meckel-Gruber syndrome (MKS) is an autosomal recessive, usually lethal multisystemic disorder characterized by early developmental anomalies of the central nervous system, cystic kidney dysplasia, hepatobiliary ductal plate malformation, and postaxial polydactyly. Three MKS loci have been mapped and recently, two genes were identified: MKS1 on 17q22 in Caucasian kindreds and MKS3 on 8q22 in Omani and Pakistani families, putting MKS on the growing list of ciliary disorders ("ciliopathies"). We performed linkage analysis for MKS1-3 in 14 consanguineous and/or multiplex families of different ethnic origins with histologic diagnosis and at least three classic MKS manifestations in each kindred.