Common Clinical Characteristics and Rare Medical Problems of Fragile X Syndrome in Thai Patients and Review of the Literature

Table 4

Rare medical problems observed in patients with FXS in this study and previous reports.

Medical problem	Number of patients in our study	Previous patient report(s)
Tetralogy of Fallot	1	(i) No previous report in PubMed
Medulloblastoma	1	(i) Garrè et al. 2009 [22] reported an 18-month-old boy with FXS and medulloblastoma with extensive nodularity; (ii) Alexiou et al. 2012 [23] reported an 11-year-old boy with methylation mosaicism for FXS and medulloblastoma
Sotos syndrome-like	2	(i) Beemer et al. 1986 [24] reported 2 boys with overgrowth, macrocephaly, minor facial anomalies and mild retardation, who were clinically diagnosed as Sotos syndrome and cytogenetic analysis results revealed fra(X)(q27)
Prader-Willi syndrome-like	3	(i) de Vries et al. 1993 [25] reported a patient with FXS when analyzing the DNA of 26 patients with suspected Prader-Willi syndrome but no abnormalities of chromosome 15. The authors also described 8 other patients with FXS and a Prader-Willi syndrome-like phenotype
Esotropia	1	(i) Hatton et al. 1998 [26] reported 8% of boys with FXS with strabismus
Astigmatism and hypermetropia	1	(i) Hatton et al. 1998 [26] reported 17% of boys with FXS with primarily hyperopia and astigmatism
Bilateral ptosis	1	Ptosis was described in previous literature [4]
Hypothyroidism	1	(i) Bregman et al. 1990 [27] reported blunted TSH response to thyrotropin releasing hormone in FXS subjects, suggesting subtle dysfunction within the hypothalamic-pituitary-thyroid axis
Bilateral conductive hearing loss	1	(i) Alanay et al. 2007 [14] reported 5 males with FXS and minimal conductive hearing loss
Cleft palate	1	Cleft palate was described in previous literature [4, 5]. It was also reported in patients with other anomalies: (i) Loesch et al. 1992 [28] reported a fragile X family with cleft lip and palate, digital and facial anomalies, and epilepsy; (ii) Giampietro et al. 1996 [29] reported a 5-year-old boy with bilateral cleft lip and palate, ventricular septal defect, and a hypoplastic thumb
Depressive disorder	1	(i) Tranebjærg and Ørum 1991 [30] reported 3 adult males with FXS and major depressive disorder
Precocious puberty	1	(i) Butler and Najjar 1988 [31] reported an 8 1/2-year-old girl with precocious puberty and a unilateral ovarian cyst; (ii) Moore et al. 1990 [32] reported a 2.8-year-old girl with early breast development, enlarged uterus and ovaries, and changes of hormonal profiles associated with true precocious puberty; (iii) Kowalczyk et al. 1996 [33] reported a 10-year and 10-month-old girl with precocious puberty
Primary amenorrhea	1	(i) No previous report in PubMed
Rectal cancer	1	(i) Phelan et al. 1988 [34] reported mucin-producing adenocarcinoma of the colon in a 14-year-old male with FXS

A 6-year-and-6-month-old boy had tetralogy of Fallot and was a mosaic for FM and PM, An 8-year-old boy had medulloblastoma with neuronal and glial differentiation, consistent with WHO grade IV, A 6-year-8-month-old boy had bilateral conductive hearing loss and cleft palate, A male was diagnosed with FXS at 11 years old and was suspected of depressive disorder at 23 years old, A 1-year-old girl had breast development (Tanner III) and mild coarse facies, A 40-year-old female had severe mental retardation, obesity, mild coarse facies, and primary amenorrhea. Her karyotype was 46,XX. No other investigation such as hormonal study to identify cause of primary amenorrhea, A 72-year-old female was diagnosed with adenocarcinoma of the rectum at 71 years of age.